Indian Dental Academy: will be one of the most relevant and exciting training center with best faculty and flexible training programs for dental professionals who wish to advance in their dental practice,Offers certified courses in Dental implants,Orthodontics,Endodontics,Cosmetic Dentistry, Prosthetic Dentistry, Periodontics and General Dentistry.
Indian Dental Academy: will be one of the most relevant and exciting training center with best faculty and flexible training programs for dental professionals who wish to advance in their dental practice,Offers certified courses in Dental implants,Orthodontics,Endodontics,Cosmetic Dentistry, Prosthetic Dentistry, Periodontics and General Dentistry.
Indian Dental Academy: will be one of the most relevant and exciting training center with best faculty and flexible training programs for dental professionals who wish to advance in their dental practice,Offers certified courses in Dental implants,Orthodontics,Endodontics,Cosmetic Dentistry, Prosthetic Dentistry, Periodontics and General Dentistry.
Oral cancer in india continues in epidemic proportions evidence base and pol...Axex Dental
Oral cancer poses a major public health challenge in India, which has the highest incidence and mortality rates in the world. Approximately 70,000 new oral cancer cases and 48,000 deaths occur yearly in India. Tobacco use, including smokeless tobacco and betel nut chewing, as well as alcohol consumption are the primary risk factors and account for over 90% of oral cancer cases in India. While India has advanced cancer treatment centers, access remains limited and prevention efforts should focus on health education, early detection, and reducing tobacco and alcohol use. A multi-sector policy approach is needed to address this growing epidemic.
The document summarizes the risk factors and prevention strategies of oral cancer in India. It finds that oral cancer is the most common cancer in India, accounting for 4 in 10 cancers. India has a high prevalence due to widespread tobacco consumption, especially gutka and quid. About 130,000 people die from oral cancer annually in India. Prevention strategies such as reducing tobacco consumption and early detection are needed to reduce the oral cancer burden.
This document provides information on population-based screening for oral cancer. It discusses the high incidence of oral cancer in India and risk factors like tobacco and alcohol. Screening methods like questionnaires, oral examination and biopsy are described. Oral examination is an effective low-cost screening method with good sensitivity and specificity. Screening aims to detect oral cancer early and prevent malignant transformation of potentially malignant lesions through tobacco cessation programs. High-risk groups like tobacco and alcohol users should be screened regularly.
Oral cancer is a term used for cancers occurring in the oral cavity. It is the most common type of head and neck cancer. Risk factors for oral cancer include tobacco use, heavy alcohol consumption, human papillomavirus infection, and sun exposure. Data from the SEER program shows that from 2002-2006 the age-adjusted incidence of oral cancer in the United States was 10.4 per 100,000 people, while the age-adjusted mortality rate was 2.6 per 100,000. Survival rates are lower for advanced stage cancers, cancers in black males, and HPV-negative tonsillar cancers.
HIV causes AIDS by attacking CD4 cells of the immune system. It enters cells through binding to CD4 and CXCR4/CCR5 receptors, integrating its RNA into the cell's DNA. This leads to increased viral load and decreased CD4 count over many years until opportunistic infections define AIDS. Globally, HIV has infected over 75 million people and claimed over 32 million lives since the early 1980s.
This document discusses cancer, including categories of cancer, signs and symptoms, frequency and common cancers worldwide and in India. It summarizes that carcinomas arise from epithelial cells, sarcomas from connective tissues, and lymphomas from immune/bone marrow cells. The highest global cancer rates occur in Northern Europe and Australia. Lung cancer is most common worldwide while breast cancer has the highest rate in Belgium. Primary prevention focuses on reducing environmental/lifestyle risk factors while secondary prevention utilizes cancer screening and registries.
Indian Dental Academy: will be one of the most relevant and exciting training center with best faculty and flexible training programs for dental professionals who wish to advance in their dental practice,Offers certified courses in Dental implants,Orthodontics,Endodontics,Cosmetic Dentistry, Prosthetic Dentistry, Periodontics and General Dentistry.
Indian Dental Academy: will be one of the most relevant and exciting training center with best faculty and flexible training programs for dental professionals who wish to advance in their dental practice,Offers certified courses in Dental implants,Orthodontics,Endodontics,Cosmetic Dentistry, Prosthetic Dentistry, Periodontics and General Dentistry.
Oral cancer in india continues in epidemic proportions evidence base and pol...Axex Dental
Oral cancer poses a major public health challenge in India, which has the highest incidence and mortality rates in the world. Approximately 70,000 new oral cancer cases and 48,000 deaths occur yearly in India. Tobacco use, including smokeless tobacco and betel nut chewing, as well as alcohol consumption are the primary risk factors and account for over 90% of oral cancer cases in India. While India has advanced cancer treatment centers, access remains limited and prevention efforts should focus on health education, early detection, and reducing tobacco and alcohol use. A multi-sector policy approach is needed to address this growing epidemic.
The document summarizes the risk factors and prevention strategies of oral cancer in India. It finds that oral cancer is the most common cancer in India, accounting for 4 in 10 cancers. India has a high prevalence due to widespread tobacco consumption, especially gutka and quid. About 130,000 people die from oral cancer annually in India. Prevention strategies such as reducing tobacco consumption and early detection are needed to reduce the oral cancer burden.
This document provides information on population-based screening for oral cancer. It discusses the high incidence of oral cancer in India and risk factors like tobacco and alcohol. Screening methods like questionnaires, oral examination and biopsy are described. Oral examination is an effective low-cost screening method with good sensitivity and specificity. Screening aims to detect oral cancer early and prevent malignant transformation of potentially malignant lesions through tobacco cessation programs. High-risk groups like tobacco and alcohol users should be screened regularly.
Oral cancer is a term used for cancers occurring in the oral cavity. It is the most common type of head and neck cancer. Risk factors for oral cancer include tobacco use, heavy alcohol consumption, human papillomavirus infection, and sun exposure. Data from the SEER program shows that from 2002-2006 the age-adjusted incidence of oral cancer in the United States was 10.4 per 100,000 people, while the age-adjusted mortality rate was 2.6 per 100,000. Survival rates are lower for advanced stage cancers, cancers in black males, and HPV-negative tonsillar cancers.
HIV causes AIDS by attacking CD4 cells of the immune system. It enters cells through binding to CD4 and CXCR4/CCR5 receptors, integrating its RNA into the cell's DNA. This leads to increased viral load and decreased CD4 count over many years until opportunistic infections define AIDS. Globally, HIV has infected over 75 million people and claimed over 32 million lives since the early 1980s.
This document discusses cancer, including categories of cancer, signs and symptoms, frequency and common cancers worldwide and in India. It summarizes that carcinomas arise from epithelial cells, sarcomas from connective tissues, and lymphomas from immune/bone marrow cells. The highest global cancer rates occur in Northern Europe and Australia. Lung cancer is most common worldwide while breast cancer has the highest rate in Belgium. Primary prevention focuses on reducing environmental/lifestyle risk factors while secondary prevention utilizes cancer screening and registries.
Dr. Angelo Consiglio owns and practices at Allergy Ear Nose & Throat near Key West, Florida, and also serves as a lecturer on oral cancer and related topics. Statistics show the risk of oral cancer increases after age 55 and is twice as high for men than women. Certain genetic mutations and lifestyle factors like smoking, drinking alcohol, a lack of fruits and vegetables in the diet, and prolonged sun exposure can contribute to higher risks of developing oral cancer.
Pattern of Head and Neck Cancer in a Tertiary Institution in Lagos Nigeriaiosrjce
IOSR Journal of Dental and Medical Sciences is one of the speciality Journal in Dental Science and Medical Science published by International Organization of Scientific Research (IOSR). The Journal publishes papers of the highest scientific merit and widest possible scope work in all areas related to medical and dental science. The Journal welcome review articles, leading medical and clinical research articles, technical notes, case reports and others.
Cervical cancer is the second most common cancer among women worldwide. It is caused by human papilloma virus, which is found in over 95% of cervical cancer cases. Risk factors include early marriage and childbearing, multiple sexual partners, long-term oral contraceptive use, lower socioeconomic status, and genital warts. The disease is most common in women aged 25 to 45 in developing regions like Latin America, sub-Saharan Africa, and Southeast Asia.
Oral cancer is a major public health issue globally and in India. It is the 8th most common cancer worldwide and the 3rd most common cancer in South-Central Asia. India has a high prevalence of oral cancer due to use of tobacco, betel quid, smoking and indigenous oral habits. Studies in India find oral cancer incidence as high as 19 per 100,000 annually. Risk factors include tobacco use, smoking, alcohol, betel quid chewing, HPV infection, and nutritional deficiencies. Men are twice as likely as women to develop oral cancer due to higher rates of tobacco and alcohol use.
Knowledge, Attitude and Practice toward Cervical Cancer and Cervical Cancer S...ijtsrd
BACKGROUND Invasive Cervical Cancer ICC has been identified as the second most common cause of morbidity and mortality compared to other cancers among women in Cameroon. Cervical cancer can be treated e ectively if diagnosed early. Less than half the number of participants presented with good practice.The correlation between participants’ knowledge, attitude and practice showed that there was a significant association which therefore provides sufficient evidence to reject the null hypothesis. The result obtained in this study indicates how useful it will be to establish health education programs to increase women’s awareness and knowledge about cervical cancer. Fongang Che Landis | Enow-Orock George | Njajou Omer | Ngowe Ngowe Marcelin "Knowledge, Attitude and Practice toward Cervical Cancer and Cervical Cancer Screening and Its Associated Factors among Women in the City of Bamenda, Cameroon" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-5 | Issue-4 , June 2021, URL: https://www.ijtsrd.compapers/ijtsrd43667.pdf Paper URL: https://www.ijtsrd.commedicine/other/43667/knowledge-attitude-and-practice-toward-cervical-cancer-and-cervical-cancer-screening-and-its-associated-factors-among-women-in-the-city-of-bamenda-cameroon/fongang-che-landis
Epidemiology of oral cancer, cancer registry in India,Global Initiatives,Tobacco,Tobacco cessation centre,WHO framework,National Tobacco Control Programme,Squamous cell carcinoma,Leukoplakia, Benign,Malignant,Epidemiology,World
This document defines cancer and its major categories. It provides worldwide statistics on cancer incidence and mortality. The most common cancers by gender and region are described. Environmental and genetic factors that can cause cancer are discussed. Methods of cancer prevention, screening, and treatment are outlined. Two specific cancers - oral and stomach cancer - are summarized in terms of epidemiology, causes, diagnosis, and prevention.
Levels of Dichlorodiphenyltrichloroethane (DDT) and Hexachlorocyclohexane (HC...Premier Publishers
Serum levels of Dichlorodiphenyltrichloroethane (DDT) and Hexachlorocyclohexane (HCH) of breast cancer patients and controls were compared with a view to determining association between exposure of organochlorine pesticides (OCPs) and breast cancer. Fifty breast cancer patients and fifty age-matched control women were recruited from the Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria. Questionnaires were administered to collect information on demography and essential breast cancer risk factors. Five millilitres of blood was collected from each participant and the serum was analysed for DDT and HCH using Gas Chromatography coupled with Electron Capture Detector. The results showed that almost all case women had no identifiable risk factors for breast cancer. The median DDT levels among case and control women were 11.87 ppb and 6.395 ppb, respectively. The levels of δ-HCH among case and control women were 5.82 ppb and 0.00 ppb while that of γ-HCH were 10.84 ppb and 0.00 ppb, respectively. This study confirmed exposure to OCPs among the studied population and revealed significantly higher levels (p≤0.05) in case women than controls, thereby, suggesting that exposure to OCPs may be a significant risk factor for breast cancer in Nigeria.
The document discusses various topics related to cancer epidemiology. It provides statistics showing that lung, breast, colon, stomach, prostate, liver and cervix cancers are among the most common types of cancer. It also discusses factors contributing to cancer deaths, finding that tobacco use accounts for 30%, diet 35%, infections 10%, and other factors like occupation, pollution and genetics account for smaller percentages. The document also discusses associations between specific cancers and factors like infections, radiation, chemicals, diet, obesity and geography.
Premalignant Lesions of Oral Cavity - A Clinicopathological Study by Mohit Srivastava in Experiments in Rhinology & Otolaryngology
We conducted a study on a total of 360 patients to find out the incidence of premalignant disorders in the oral cavity who attended the ENT opd of Saraswathi Institute of Medical Sciences, Hapur. The study design was cross sectional in nature. Out of all the 360 patients who were suspected to have premalignant disorders of oral cavity were subjected to biopsy and 87 of them were found to be premalignant. Incidence was found to be 24.53% in males and 23.6% in females. Buccal mucosa was most common site of involvement.
https://crimsonpublishers.com/ero/fulltext/ERO.000515.php
Cancer epidemiology is the study of cancer occurrence and distribution in human populations. Some key points from the document include:
- The earliest known descriptions of cancer come from ancient Egyptian medical texts from 3000-1500 BC.
- Important historical discoveries in cancer epidemiology include linking tobacco smoking to lung cancer in 1950 and occupations like chimney sweeping to scrotum cancer in 1775.
- Common sources of cancer epidemiology data include registries like SEER in the US and IARC internationally, which provide statistics on incidence, mortality, survival rates.
- Cancer risk varies based on age, sex, race, and other demographic factors. Globally, lung cancer is the most commonly diagnosed cancer while breast
Background: The incidence of cancers is increasing worldwide, particularly in the developing countries as shown by recent cancer stastics from the WHO. It is even anticipated that with the increase in life expentancy, consequent upon inproved standard of living and globalization, the burden of cancers will increase within this millenium. With respective to cancer of the prostate, it is the most common type of cancer in urology. In developing countries, diagnostic is done at a late stage of evolution. In Cameroon, data on prostate cancer are scanty whereas the incidence of this disease is increasing. Objective: This article is designed to describe the epidemiological features of prostate cancer at the General Hospital of Yaoundé. Patients and methods: A 4-year retrospective study of patients seen with the diagnosis of cancer at the Medical Oncology unit of the Yaoundé General Hospital between January 2012 and December 2015. The demographic pattern (age of patients, socio professional activity, marital status), clinical features (cancer diagnosis), treatment modalities and outcome were studied. Main results: Of the 7 775 patients enrolled in the Medical Oncology Service over the study period, 1.4% (n = 108) cases of prostate cancer were seen. The prevalence over the study period was 1.38% and a relatively large annual growth of cases with an annual average of 27 cases was noted. The average age of patients was 67.82 years with a range of 34-83 years. The commonest presenting symptoms were the urinary frequency (54.63%) whereas the least common were fatigue (05.5%) and straining (03.70%). PSA was obtained in 49 patients, representing about 45.4% of all patients. Only 14 (01.26%) had biopsy reports. Conclusion: Prostate cancer is a major problem facing the aging male, and inadequate facilities make early detection difficult. Therefore, treatment is mainly palliative because of late diagnosis.
Cancer is characterized by abnormal cell growth and the ability to invade other tissues. Global cancer incidence is estimated at 12.1 million new cases in 2007, with lung cancer the leading site. Cancer deaths were estimated at 7.6 million in 2007. In Pakistan, common cancers include blood, esophageal, oral, breast, colon and lung cancers. Cancer development occurs in phases from healthy cells to localized cancer to spread. Prevention, screening, early diagnosis, treatment and palliation are important for an integrated cancer control strategy. Lifestyle and environmental factors like diet, radiation, chemicals and viruses can cause cancer. Primary prevention focuses on public education and legislation while secondary prevention emphasizes early diagnosis through screening programs.
Aboriginal Patterns of Cancer Care Project Breast Cancer paper BMCCancer 1471...Cancer Council NSW
Aboriginal women in New South Wales, Australia have lower rates of survival from breast cancer than non-Aboriginal women. Aboriginal women were less likely to receive surgical treatment for their breast cancer and were more likely to have other health issues. After accounting for differences in factors like age, disease stage at diagnosis, surgical treatment, and health issues, Aboriginal women still had a 30% higher risk of death from breast cancer. Improving access to surgical treatment and reducing health issues may help increase breast cancer survival rates for Aboriginal women.
Melanoma epidemiology, etiopathogenesis and prevention - Professor Torello L...VR Foundation
This document summarizes epidemiological data and risk factors related to melanoma. It discusses that melanoma incidence has increased significantly in fair-skinned populations over the last century. Genetic factors like mutations in the CDKN2A and CDK4 genes confer high penetrance for melanoma risk, while variants in the MC1R gene are a low penetrance risk factor. Environmental exposures like ultraviolet radiation from the sun are important exogenous risk factors for developing melanoma.
Oral cancer awareness and knowledge in adults attending a dental hospital in ...Apollo Hospitals
Cancer, being one of the most common causes of death after
coronary heart diseases, causes nearly 7 million deaths each
year worldwide and according to WHO, presently, almost 25
million people are suffering from cancer, and by 2020 it is
projected that there may be 16 million new cancer cases and
ten million cancer deaths reported every year.1 In most
countries, one to ten cases per 1,00,000 people are diagnosed
with oral cancer every year. Though, it accounts for only two
percent of all cancers reported worldwide, it is the second
most common cancer in males and the fourth most common
cancer in females in South-Central Asia, accounting for seven
percent of the total cancers diagnosed in this region, ranking
among the three most common types of cancers reported in
the region.2 With 75,000e80,000 new cases of oral cancers
being reported every year, India has the highest prevalence of
oral cancer in the world. According GLOBOCON 2012 report,
oral cancer is a third most frequent cancer after breast and
cervix with an estimated 5-year prevalence rate of 6.6%.3 In
India, Northeast India including Assam accounts for more
than 40% of these cases.4 Oral cancer has a higher cure rate
when detected early and treated accordingly, but unfortu-
nately most oral cancers are diagnosed in advanced stages,
requiring aggressive treatment and associated morbidity,
resulting in higher mortality rates.
Burden of Cervical Cancer & other HPV Related Diseases : Indian Perspectiv...Lifecare Centre
HPV RELATED DISEASES
Human papillomavirus (HPV) infection is now a well-established cause of cervical cancer. HPV causes virtually 100% of cervical cancer cases
There is growing evidence of HPV being a relevant factor in other ANOGENITAL CANCERS (anus, vulva, vagina and penis) and head and neck cancers.
HPV is also responsible for other diseases such as recurrent juvenile respiratory papillomatosis and genital warts
This document discusses strategies for preventing oral cancer, including controlling risk factors like smoking, alcohol use, and HPV infection. It notes that oral cancer has multiple potential causes, making prevention difficult. The main risk factor is tobacco use, which accounts for over 90% of oral cancer cases. Quitting smoking significantly reduces cancer risks over time, with risks dropping by half after 10-15 years of abstinence. As dental professionals, the document recommends following the "5 A's" approach of asking patients about tobacco use, advising them to quit, assessing willingness to quit, assisting with a plan to quit, and arranging follow-up support.
Chemotherapy uses anti-cancer drugs to destroy cancer cells. It can be curative for some cancers like leukemias, Wilms tumor, and Hodgkin's lymphoma. The drugs work by interfering with cell division through different mechanisms and can be cell cycle specific or non-specific. Alkylating agents are a common class of chemotherapy drugs that work by transferring alkyl groups to DNA, causing cross-linkages and strand breaks to damage DNA and inhibit cell proliferation. Combination chemotherapy and intermittent dosing regimens are often used to improve outcomes.
This document discusses various topics related to antimicrobial agents including classification, mechanisms of action, uses, and adverse effects. It describes different classes of antibiotics such as beta-lactams, sulfonamides, fluoroquinolones, and their characteristics. It provides information on classification based on source and mechanism of action. Common uses and adverse effects of these antibiotics are also summarized. The document also includes several multiple choice questions related to antimicrobial therapy.
Oncology Immunotherapy - Nivolumab and other PD-1/PD-L1 Targeted Agents (061213)Will Roettger
This is a short briefing on the oncology immunotherapy PD-1/PD-L1 targeted agents currently under development. In this briefing we look at the competitive landscape, PD-1/PD-L1 product profiles, positioning, strategy, as well as a development timeline and SWOT on the BMS PD-1 blocker nivolumab. Updates to this briefing will come as newer information is discovered.
Dr. Angelo Consiglio owns and practices at Allergy Ear Nose & Throat near Key West, Florida, and also serves as a lecturer on oral cancer and related topics. Statistics show the risk of oral cancer increases after age 55 and is twice as high for men than women. Certain genetic mutations and lifestyle factors like smoking, drinking alcohol, a lack of fruits and vegetables in the diet, and prolonged sun exposure can contribute to higher risks of developing oral cancer.
Pattern of Head and Neck Cancer in a Tertiary Institution in Lagos Nigeriaiosrjce
IOSR Journal of Dental and Medical Sciences is one of the speciality Journal in Dental Science and Medical Science published by International Organization of Scientific Research (IOSR). The Journal publishes papers of the highest scientific merit and widest possible scope work in all areas related to medical and dental science. The Journal welcome review articles, leading medical and clinical research articles, technical notes, case reports and others.
Cervical cancer is the second most common cancer among women worldwide. It is caused by human papilloma virus, which is found in over 95% of cervical cancer cases. Risk factors include early marriage and childbearing, multiple sexual partners, long-term oral contraceptive use, lower socioeconomic status, and genital warts. The disease is most common in women aged 25 to 45 in developing regions like Latin America, sub-Saharan Africa, and Southeast Asia.
Oral cancer is a major public health issue globally and in India. It is the 8th most common cancer worldwide and the 3rd most common cancer in South-Central Asia. India has a high prevalence of oral cancer due to use of tobacco, betel quid, smoking and indigenous oral habits. Studies in India find oral cancer incidence as high as 19 per 100,000 annually. Risk factors include tobacco use, smoking, alcohol, betel quid chewing, HPV infection, and nutritional deficiencies. Men are twice as likely as women to develop oral cancer due to higher rates of tobacco and alcohol use.
Knowledge, Attitude and Practice toward Cervical Cancer and Cervical Cancer S...ijtsrd
BACKGROUND Invasive Cervical Cancer ICC has been identified as the second most common cause of morbidity and mortality compared to other cancers among women in Cameroon. Cervical cancer can be treated e ectively if diagnosed early. Less than half the number of participants presented with good practice.The correlation between participants’ knowledge, attitude and practice showed that there was a significant association which therefore provides sufficient evidence to reject the null hypothesis. The result obtained in this study indicates how useful it will be to establish health education programs to increase women’s awareness and knowledge about cervical cancer. Fongang Che Landis | Enow-Orock George | Njajou Omer | Ngowe Ngowe Marcelin "Knowledge, Attitude and Practice toward Cervical Cancer and Cervical Cancer Screening and Its Associated Factors among Women in the City of Bamenda, Cameroon" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-5 | Issue-4 , June 2021, URL: https://www.ijtsrd.compapers/ijtsrd43667.pdf Paper URL: https://www.ijtsrd.commedicine/other/43667/knowledge-attitude-and-practice-toward-cervical-cancer-and-cervical-cancer-screening-and-its-associated-factors-among-women-in-the-city-of-bamenda-cameroon/fongang-che-landis
Epidemiology of oral cancer, cancer registry in India,Global Initiatives,Tobacco,Tobacco cessation centre,WHO framework,National Tobacco Control Programme,Squamous cell carcinoma,Leukoplakia, Benign,Malignant,Epidemiology,World
This document defines cancer and its major categories. It provides worldwide statistics on cancer incidence and mortality. The most common cancers by gender and region are described. Environmental and genetic factors that can cause cancer are discussed. Methods of cancer prevention, screening, and treatment are outlined. Two specific cancers - oral and stomach cancer - are summarized in terms of epidemiology, causes, diagnosis, and prevention.
Levels of Dichlorodiphenyltrichloroethane (DDT) and Hexachlorocyclohexane (HC...Premier Publishers
Serum levels of Dichlorodiphenyltrichloroethane (DDT) and Hexachlorocyclohexane (HCH) of breast cancer patients and controls were compared with a view to determining association between exposure of organochlorine pesticides (OCPs) and breast cancer. Fifty breast cancer patients and fifty age-matched control women were recruited from the Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria. Questionnaires were administered to collect information on demography and essential breast cancer risk factors. Five millilitres of blood was collected from each participant and the serum was analysed for DDT and HCH using Gas Chromatography coupled with Electron Capture Detector. The results showed that almost all case women had no identifiable risk factors for breast cancer. The median DDT levels among case and control women were 11.87 ppb and 6.395 ppb, respectively. The levels of δ-HCH among case and control women were 5.82 ppb and 0.00 ppb while that of γ-HCH were 10.84 ppb and 0.00 ppb, respectively. This study confirmed exposure to OCPs among the studied population and revealed significantly higher levels (p≤0.05) in case women than controls, thereby, suggesting that exposure to OCPs may be a significant risk factor for breast cancer in Nigeria.
The document discusses various topics related to cancer epidemiology. It provides statistics showing that lung, breast, colon, stomach, prostate, liver and cervix cancers are among the most common types of cancer. It also discusses factors contributing to cancer deaths, finding that tobacco use accounts for 30%, diet 35%, infections 10%, and other factors like occupation, pollution and genetics account for smaller percentages. The document also discusses associations between specific cancers and factors like infections, radiation, chemicals, diet, obesity and geography.
Premalignant Lesions of Oral Cavity - A Clinicopathological Study by Mohit Srivastava in Experiments in Rhinology & Otolaryngology
We conducted a study on a total of 360 patients to find out the incidence of premalignant disorders in the oral cavity who attended the ENT opd of Saraswathi Institute of Medical Sciences, Hapur. The study design was cross sectional in nature. Out of all the 360 patients who were suspected to have premalignant disorders of oral cavity were subjected to biopsy and 87 of them were found to be premalignant. Incidence was found to be 24.53% in males and 23.6% in females. Buccal mucosa was most common site of involvement.
https://crimsonpublishers.com/ero/fulltext/ERO.000515.php
Cancer epidemiology is the study of cancer occurrence and distribution in human populations. Some key points from the document include:
- The earliest known descriptions of cancer come from ancient Egyptian medical texts from 3000-1500 BC.
- Important historical discoveries in cancer epidemiology include linking tobacco smoking to lung cancer in 1950 and occupations like chimney sweeping to scrotum cancer in 1775.
- Common sources of cancer epidemiology data include registries like SEER in the US and IARC internationally, which provide statistics on incidence, mortality, survival rates.
- Cancer risk varies based on age, sex, race, and other demographic factors. Globally, lung cancer is the most commonly diagnosed cancer while breast
Background: The incidence of cancers is increasing worldwide, particularly in the developing countries as shown by recent cancer stastics from the WHO. It is even anticipated that with the increase in life expentancy, consequent upon inproved standard of living and globalization, the burden of cancers will increase within this millenium. With respective to cancer of the prostate, it is the most common type of cancer in urology. In developing countries, diagnostic is done at a late stage of evolution. In Cameroon, data on prostate cancer are scanty whereas the incidence of this disease is increasing. Objective: This article is designed to describe the epidemiological features of prostate cancer at the General Hospital of Yaoundé. Patients and methods: A 4-year retrospective study of patients seen with the diagnosis of cancer at the Medical Oncology unit of the Yaoundé General Hospital between January 2012 and December 2015. The demographic pattern (age of patients, socio professional activity, marital status), clinical features (cancer diagnosis), treatment modalities and outcome were studied. Main results: Of the 7 775 patients enrolled in the Medical Oncology Service over the study period, 1.4% (n = 108) cases of prostate cancer were seen. The prevalence over the study period was 1.38% and a relatively large annual growth of cases with an annual average of 27 cases was noted. The average age of patients was 67.82 years with a range of 34-83 years. The commonest presenting symptoms were the urinary frequency (54.63%) whereas the least common were fatigue (05.5%) and straining (03.70%). PSA was obtained in 49 patients, representing about 45.4% of all patients. Only 14 (01.26%) had biopsy reports. Conclusion: Prostate cancer is a major problem facing the aging male, and inadequate facilities make early detection difficult. Therefore, treatment is mainly palliative because of late diagnosis.
Cancer is characterized by abnormal cell growth and the ability to invade other tissues. Global cancer incidence is estimated at 12.1 million new cases in 2007, with lung cancer the leading site. Cancer deaths were estimated at 7.6 million in 2007. In Pakistan, common cancers include blood, esophageal, oral, breast, colon and lung cancers. Cancer development occurs in phases from healthy cells to localized cancer to spread. Prevention, screening, early diagnosis, treatment and palliation are important for an integrated cancer control strategy. Lifestyle and environmental factors like diet, radiation, chemicals and viruses can cause cancer. Primary prevention focuses on public education and legislation while secondary prevention emphasizes early diagnosis through screening programs.
Aboriginal Patterns of Cancer Care Project Breast Cancer paper BMCCancer 1471...Cancer Council NSW
Aboriginal women in New South Wales, Australia have lower rates of survival from breast cancer than non-Aboriginal women. Aboriginal women were less likely to receive surgical treatment for their breast cancer and were more likely to have other health issues. After accounting for differences in factors like age, disease stage at diagnosis, surgical treatment, and health issues, Aboriginal women still had a 30% higher risk of death from breast cancer. Improving access to surgical treatment and reducing health issues may help increase breast cancer survival rates for Aboriginal women.
Melanoma epidemiology, etiopathogenesis and prevention - Professor Torello L...VR Foundation
This document summarizes epidemiological data and risk factors related to melanoma. It discusses that melanoma incidence has increased significantly in fair-skinned populations over the last century. Genetic factors like mutations in the CDKN2A and CDK4 genes confer high penetrance for melanoma risk, while variants in the MC1R gene are a low penetrance risk factor. Environmental exposures like ultraviolet radiation from the sun are important exogenous risk factors for developing melanoma.
Oral cancer awareness and knowledge in adults attending a dental hospital in ...Apollo Hospitals
Cancer, being one of the most common causes of death after
coronary heart diseases, causes nearly 7 million deaths each
year worldwide and according to WHO, presently, almost 25
million people are suffering from cancer, and by 2020 it is
projected that there may be 16 million new cancer cases and
ten million cancer deaths reported every year.1 In most
countries, one to ten cases per 1,00,000 people are diagnosed
with oral cancer every year. Though, it accounts for only two
percent of all cancers reported worldwide, it is the second
most common cancer in males and the fourth most common
cancer in females in South-Central Asia, accounting for seven
percent of the total cancers diagnosed in this region, ranking
among the three most common types of cancers reported in
the region.2 With 75,000e80,000 new cases of oral cancers
being reported every year, India has the highest prevalence of
oral cancer in the world. According GLOBOCON 2012 report,
oral cancer is a third most frequent cancer after breast and
cervix with an estimated 5-year prevalence rate of 6.6%.3 In
India, Northeast India including Assam accounts for more
than 40% of these cases.4 Oral cancer has a higher cure rate
when detected early and treated accordingly, but unfortu-
nately most oral cancers are diagnosed in advanced stages,
requiring aggressive treatment and associated morbidity,
resulting in higher mortality rates.
Burden of Cervical Cancer & other HPV Related Diseases : Indian Perspectiv...Lifecare Centre
HPV RELATED DISEASES
Human papillomavirus (HPV) infection is now a well-established cause of cervical cancer. HPV causes virtually 100% of cervical cancer cases
There is growing evidence of HPV being a relevant factor in other ANOGENITAL CANCERS (anus, vulva, vagina and penis) and head and neck cancers.
HPV is also responsible for other diseases such as recurrent juvenile respiratory papillomatosis and genital warts
This document discusses strategies for preventing oral cancer, including controlling risk factors like smoking, alcohol use, and HPV infection. It notes that oral cancer has multiple potential causes, making prevention difficult. The main risk factor is tobacco use, which accounts for over 90% of oral cancer cases. Quitting smoking significantly reduces cancer risks over time, with risks dropping by half after 10-15 years of abstinence. As dental professionals, the document recommends following the "5 A's" approach of asking patients about tobacco use, advising them to quit, assessing willingness to quit, assisting with a plan to quit, and arranging follow-up support.
Chemotherapy uses anti-cancer drugs to destroy cancer cells. It can be curative for some cancers like leukemias, Wilms tumor, and Hodgkin's lymphoma. The drugs work by interfering with cell division through different mechanisms and can be cell cycle specific or non-specific. Alkylating agents are a common class of chemotherapy drugs that work by transferring alkyl groups to DNA, causing cross-linkages and strand breaks to damage DNA and inhibit cell proliferation. Combination chemotherapy and intermittent dosing regimens are often used to improve outcomes.
This document discusses various topics related to antimicrobial agents including classification, mechanisms of action, uses, and adverse effects. It describes different classes of antibiotics such as beta-lactams, sulfonamides, fluoroquinolones, and their characteristics. It provides information on classification based on source and mechanism of action. Common uses and adverse effects of these antibiotics are also summarized. The document also includes several multiple choice questions related to antimicrobial therapy.
Oncology Immunotherapy - Nivolumab and other PD-1/PD-L1 Targeted Agents (061213)Will Roettger
This is a short briefing on the oncology immunotherapy PD-1/PD-L1 targeted agents currently under development. In this briefing we look at the competitive landscape, PD-1/PD-L1 product profiles, positioning, strategy, as well as a development timeline and SWOT on the BMS PD-1 blocker nivolumab. Updates to this briefing will come as newer information is discovered.
The document summarizes immunotherapy approaches for treating cancer patients, including therapeutic vaccines, passive immunotherapy using monoclonal antibodies, and adoptive cell transfer therapy. It discusses antigens targeted by vaccines, types of vaccines like whole cell, peptide, and dendritic cell vaccines, and adjuvants used to stimulate immune responses. It also notes challenges faced by immunotherapy like tumor evasion mechanisms and the need for clinical efficacy data.
This document provides an overview of immunotherapy for cancer. It discusses how immunotherapy works by boosting the body's natural immune response against cancer cells. The main types of immunotherapy discussed are monoclonal antibodies, cancer vaccines, and non-specific immunotherapies like cytokines and interferons. Monoclonal antibodies are engineered antibodies that target specific antigens on cancer cells, while cancer vaccines are designed to trigger an immune response against tumor antigens. Together, these immunotherapies help the immune system better recognize and destroy cancer cells.
Immunotherapy involves activating or suppressing the immune system to fight diseases like cancer. There are two main types - activation immunotherapies that elicit an immune response and suppression immunotherapies that reduce it. Methods include monoclonal antibodies, cancer vaccines, cytokines, and immunomodulators that control immune response levels. The goal is to stimulate the immune system to attack tumor cells through approaches like naked or conjugated monoclonal antibodies, cancer vaccines, and nonspecific therapies including cytokines and interleukins.
The document discusses various approaches to immunotherapy in cancers, including targeted therapies, biologic therapies, angiogenesis inhibitors, and immune-based therapies. It describes cellular processes like the cell cycle and cell kinetics that are relevant for cancer growth. It provides details on specific targeted therapies for pathways like EGFR, HER2/neu, VEGF, and PI3K/Akt/mTOR that are dysregulated in cancers. Immunotherapies like HPV vaccines have been successful in preventing cervical cancers associated with HPV infection. Overall, the document outlines current understandings and therapeutic approaches regarding tumor proliferation and immunotherapies for cancer.
A detailed ppt about cancer immunotherapy.
includes:-
Immunosurveillance and Immunoediting
Dentritic cell vaccines
Antibody therapy
Combined therapy
immune blockades
Cytokine therapy
T cell therapy
Include latest research finding about therapy.
This document discusses cancer immunotherapy. It begins by describing tumor antigens that can be recognized by the immune system, such as tumor-specific antigens, tumor-associated antigens, and antigens from oncogenic viruses. It then discusses how tumors evade the immune system and various approaches to immunotherapy, including active immunotherapies using vaccines made of tumor cells, purified antigens, or antigen-loaded dendritic cells. Passive immunotherapies discussed include adoptive cellular therapy, monoclonal antibodies, and immunotoxins. Clinical trials and effectiveness of different immunotherapies are also summarized.
Cancer immunotherapy uses the immune system to fight cancer. It stimulates the patient's immune system to attack and reject tumor cells. William Coley first observed in the late 1800s that some cancer patients who got infections after surgery saw their cancer improve. This led him to try treating patients by infecting them with bacteria, known as Coley toxins. Modern immunotherapy includes monoclonal antibody therapies like rituximab that target specific proteins on cancer cells, cancer vaccines, and cytokines to boost the immune system. Researchers are also exploring newer monoclonal antibodies and using cloned immune cells from patients to treat their cancer.
Immunotherapy is a type of cancer treatment that uses components of the immune system to fight cancer. There are several types of immunotherapy including passive immunotherapy using monoclonal antibodies that target tumor antigens, active immunotherapies using cytokines, cancer vaccines, and cell-based therapies. Monoclonal antibodies can directly kill cancer cells, block proteins that help cancer grow, or be linked to chemotherapy drugs. Cancer vaccines work by boosting the immune system against tumor antigens. Adoptive immunotherapy transfers modified immune cells to the body to attack cancer. Immunotherapy has shown success in treating various cancer types and continues to be improved and developed further.
Chemotherapy involves the use of cytotoxic drugs to treat cancer. The goals of chemotherapy are to cure cancer, improve survival rates, or relieve symptoms. Key principles of chemotherapy include: (1) using drug combinations to increase efficacy and decrease resistance, (2) treating micrometastatic disease early on, and (3) dose intensity being important for response. Adjuvant chemotherapy after surgery or radiation has improved survival rates for several cancers like breast cancer and osteosarcoma by targeting remaining micrometastatic disease.
Indian Dental Academy: will be one of the most relevant and exciting training center with best faculty and flexible training programs for dental professionals who wish to advance in their dental practice,Offers certified courses in Dental implants,Orthodontics,Endodontics,Cosmetic Dentistry, Prosthetic Dentistry, Periodontics and General Dentistry.
This document discusses tobacco-related oral cancer and precancerous conditions. It begins with an introduction to oral cancer epidemiology, noting that tobacco use accounts for about 40% of oral cancer cases. It then covers the main risk factors for oral cancer like smoking, smokeless tobacco, alcohol, and betel quid chewing. The document defines several precancerous oral lesions including leukoplakia, erythroplakia, lichen planus and submucous fibrosis. It also describes several clinical trials investigating treatments for oral cancer. In summary, the document provides an overview of the epidemiology, risk factors, precancerous lesions and clinical trials related to tobacco-induced oral cancer.
This document summarizes information about oral precancer and cancer. It discusses common sites of oral cancer, established risk factors like smoking and alcohol use, and types of oral precancers and cancers. The document also briefly outlines available treatment options, signs and symptoms, staging systems, and preventive measures for oral cancer.
1. Oral cancer is a major public health problem in India, where it accounts for over 30% of all cancers. It is most commonly diagnosed at later stages, resulting in low treatment outcomes and costs for patients. 2. Tobacco use, in forms such as chewing tobacco and smoking, is the most important risk factor for oral cancer in India. 3. Efforts toward early detection of oral cancer through screening programs and prevention education on reducing tobacco use have the potential to significantly reduce the disease burden in India.
- Over the last 30 years, multidisciplinary treatment of oral and head/neck cancers involving many medical specialties has become standard practice. The main treatment modalities are surgery, radiation therapy, and chemotherapy.
- Surgical techniques for oral cancers have not changed dramatically but variations in neck surgery and mandible surgery have occurred. Reconstructive surgery using flaps and free tissue transfer allows safer and wider resections.
- Radiation therapy is now more effective and less toxic due to modern technologies that enhance tumor targeting and spare normal tissues. Fractionation alterations also improve outcomes in some cases.
Nasopharyngeal carcinoma is characterized by distinct geographical distribution and is prevalent in east and southeast Asia. Recent decades have seen declining incidence and mortality, likely due to lifestyle changes, improved understanding of risk factors, screening, and treatment advances. Population screening using plasma EBV DNA shows promise in detecting early-stage disease. Advances in imaging, intensity-modulated radiation therapy, and optimized chemotherapy have improved survival while reducing toxicities. Immune checkpoint therapies also show potential for recurrent or metastatic disease.
This document summarizes cancer epidemiology and risk factors over the life course. It notes that cancer incidence has been increasing globally and discusses the most common cancer sites among men and women. It then covers childhood cancers, cancer etiology related to tobacco use, alcohol consumption, infections, reproductive factors, diet, occupation, radiation, pollution, and other environmental exposures.
This document discusses a study investigating the anti-cancer effects of extracts from five medicinal plants - Solanum viarum, Acanthus illicifolious, Annona squamosa, Alstonia scholaris, and Calotropis gigantea. The study aims to determine the effect of leaf extracts from these plants on human breast cancer and blood cancer cell lines. Specifically, it will analyze the proliferation, viability, and morphological changes of each cancer cell line when treated with extracts from each plant. The introduction provides background on cancer and the need for alternative anti-cancer treatments due to the side effects of conventional therapies.
Studies that examined the therapeutic potential of plants leaf extracts
Plant Scientific Name Common Name Type of extraction Proposed active material
1. Solanum viarum Tropical Soda Apple Ether Solasodine glycoalkaloid
2. Acanthus illicifolious Harkucha Kanta Methanol Triterpenoids,Flavonoids,
Alkaloids
3. Annona squamosa Custard Apple Ethyl acetate Acetogenins,Alkaloids,
Dofamine
4 Alstonia scholaris. Chatium Methanol Alkaloids,Flavonoids
5. Calotropis gigantea Akanda Ethanol Triterpenoids,Flavonol
Glycosides
There are several major causes of cancer in India. Tobacco consumption, through smoking bidis and other products, is the leading cause and is responsible for close to half of all cancer cases among Indian men and one-fifth of cases among women. Other top causes include consumption of alcohol, certain viruses like HPV which cause cervical cancer, consumption of red meat and processed foods, radiation, and certain sexual and reproductive factors. The number of cancer cases is also rising in India due to an aging population and lifestyle changes associated with urbanization.
From premalignant lesions to early gastric cancerLe Grand Métier
1. Gastric cancer remains a major cause of cancer incidence and mortality worldwide, though rates have declined in many countries. However, some populations have seen increasing or stable rates, particularly in younger age groups.
2. While overall rates are decreasing in most Western countries, some subgroups have shown rising corpus-dominant gastric cancer incidence, particularly younger white women. Similar trends have emerged in countries like South Korea and Brazil.
3. Possible reasons for these trends include changing gastric microecology with reduced H. pylori infection and increased autoimmune gastritis, particularly affecting the corpus region in younger cohorts. Continued monitoring is needed to understand these emerging patterns.
February 4th worldwide is celebrated as Cancer day. The main aim of this celebration is to create awareness about cancer and reduce the burden of cancer.
Bronchopulmonary cancers are common cancers with a poor prognosis. It is the leading cause of death by cancer in Algeria and in the world. Behind this unfavorable prognosis hides numerous disparities according to age, sex, and exposure to risk factors, ranking 4th among incident cancers and developing countries including Algeria, all sexes combined. It ranks 2nd cancers in men and 3rd among women. Whatever the age observed, the incidence of this cancer is higher in men than in women, however the gap is narrowing to the detriment of the latter. The results of scientific research agree to relate trends in incidence and mortality rates to tobacco consumption, including passive smoking. Furthermore, other risk factors are mentioned such as exposure to asbestos in the workplace or to radon for the general population, or even genetic predisposition. However, the weight of these etiological and/or predisposing factors is in no way comparable to that of tobacco in the genesis of lung cancer and the resulting mortality. We provide a literature review in our article on the descriptive and analytical epidemiology of lung cancer.
This document reports a case of primary combined squamous and small cell carcinoma of the larynx and reviews 13 previously published cases. It finds that this composite tumor is extremely rare, with only 14 total reported cases. The tumors generally affect middle-aged to elderly men with a history of smoking and present with symptoms like hoarseness and neck masses. While treatment often involves surgery, radiation, and chemotherapy, the prognosis is usually poor, with most patients dying within 2 years due to early metastasis.
This document discusses head and neck cancers, which account for over 550,000 cases worldwide annually. Males are affected significantly more than females. The most common sites are the oral cavity, pharynx, and larynx. Squamous cell carcinoma makes up 90-95% of head and neck cancers. Major risk factors include smoking, alcohol consumption, HPV infection, and betel nut chewing. Evaluation involves physical examination, endoscopy, and imaging to determine the extent of the primary tumor and metastasis. Biopsy is required for diagnosis.
This document discusses head and neck cancers, which account for over 550,000 cases worldwide annually. Males are affected significantly more than females. The most common sites are the oral cavity, pharynx, and larynx. Squamous cell carcinoma makes up 90-95% of head and neck cancers. Major risk factors include smoking, alcohol consumption, HPV infection, and betel nut chewing. Evaluation involves physical examination, endoscopy, and imaging of the primary site and neck nodes. Biopsy is required for diagnosis.
This document discusses the rising incidence of oropharyngeal cancer, which is increasingly associated with human papillomavirus (HPV) infection. HPV-positive oropharyngeal cancer has distinct clinical and biological features compared to HPV-negative cancer, including younger patient age, fewer risk factors, and better prognosis. Detection of HPV status is important for prognostication and potentially de-escalating treatment intensity for HPV-positive patients due to their improved survival. Immunohistochemistry for p16 is a practical and widely applicable method for determining HPV status in clinical specimens.
Opportunity for Dentists (BDS/MDS )to relocate to United kingdom -Register as a DENTAL HYGIENIST/ DENTAL THERAPIST without Board exams and after approval you can register in GDC as a DH/DT and start working as a DH/DT Immediately and get paid.
You can complete the whole process in 3-4 months.Salary range for DH/DT is around 2500-3500 Pounds per month.
Eligibility / requirements-
1. An International English Language Testing System (IELTS) certificate
at the appropriate level.(Within 2 yrs of application date )
2: A recent primary dental qualification that has been taught and examined in English..(Within 2 yrs of application date )
3: A recent pass in a language test for registration with a regulatory authority in a country where the first language is English.
If you are interested Please contact us for more details.
1ST, 2ND AND 3RD ORDER BENDS IN STANDARD EDGEWISE APPLIANCE SYSTEM /Fixed ort...Indian dental academy
Indian Dental Academy: will be one of the most relevant and exciting training center with best faculty and flexible training programs for dental professionals
who wish to advance in their dental practice,Offers certified courses in Dental implants,Orthodontics,Endodontics,Cosmetic Dentistry, Prosthetic Dentistry,
Periodontics and General Dentistry.
Indian Dental Academy: will be one of the most relevant and exciting training center with best faculty and flexible training programs for dental professionals who wish to advance in their dental practice,Offers certified courses in Dental implants,Orthodontics,Endodontics,Cosmetic Dentistry, Prosthetic Dentistry, Periodontics and General Dentistry.
I –Aligners are made with FDA approved transparent thermoplastic materials using 3D scanning, 3D Printing and finally Trays with Pressure vacuum formers.
Dear Doctor,
Indian Dental Academy Now offers comprehensive online Orthodontics course.
Course includes:
1.whiteboard lecture presentations
2.Case Discussions
3.with hundreds of pictures.
4.Demo on Models
5.Demo on Patients
6. subtitles in your own language
12 months unlimited access and support @350 USD only.
For Demo please visit :www.idalectures.com/preview/
For more details visit: www.idalectures.com
Please contact us for any clarifications:
idalectures@gmail.com
indiandentalacademy@gmail.com
Thanks & Regards
Indian Dental Academy
--
Indian Dental Academy
Leader in continuing dental education
www.indiandentalacademy.com
skype:indiandentalacademy
+919248678078
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.for more details please visit
www.indiandentalacademy.com
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.for more details please visit
www.indiandentalacademy.com
Cytotoxicity of silicone materials used in maxillofacial prosthesis / dental ...Indian dental academy
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.for more details please visit
www.indiandentalacademy.com
Diagnosis and treatment planning in completely endntulous arches/dental coursesIndian dental academy
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.for more details please visit
www.indiandentalacademy.com
Properties of Denture base materials /rotary endodontic coursesIndian dental academy
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.for more details please visit
www.indiandentalacademy.com
Use of modified tooth forms in complete denture occlusion / dental implant...Indian dental academy
This document discusses dental occlusion concepts and philosophies for complete dentures. It introduces key terms like physiologic occlusion and defines different occlusion schemes like balanced articulation and monoplane articulation. The document discusses advantages and disadvantages of using anatomic versus non-anatomic teeth for complete dentures. It also outlines requirements for maintaining denture stability, such as balanced occlusal contacts and control of horizontal forces. The goal of occlusion for complete dentures is to re-establish the homeostasis of the masticatory system disrupted by edentulism.
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.for more details please visit
www.indiandentalacademy.com
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.for more details please visit
www.indiandentalacademy.com
This document discusses dental casting investment materials. It describes the three main types of investments - gypsum bonded, phosphate bonded, and ethyl silicate bonded investments. For gypsum bonded investments specifically, it details their classification, composition including the roles of gypsum, silica, and modifiers, setting time, normal and hygroscopic setting expansion, and thermal expansion. It provides information on how the properties of gypsum bonded investments are affected by their composition. The document serves as a comprehensive overview of dental casting investment materials.
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.for more details please visit
www.indiandentalacademy.com
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.for more details please visit
www.indiandentalacademy.com
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.for more details please visit
www.indiandentalacademy.com
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.for more details please visit
www.indiandentalacademy.com
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.for more details please visit
www.indiandentalacademy.com
Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
Integrating Ayurveda into Parkinson’s Management: A Holistic ApproachAyurveda ForAll
Explore the benefits of combining Ayurveda with conventional Parkinson's treatments. Learn how a holistic approach can manage symptoms, enhance well-being, and balance body energies. Discover the steps to safely integrate Ayurvedic practices into your Parkinson’s care plan, including expert guidance on diet, herbal remedies, and lifestyle modifications.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptxHolistified Wellness
We’re talking about Vedic Meditation, a form of meditation that has been around for at least 5,000 years. Back then, the people who lived in the Indus Valley, now known as India and Pakistan, practised meditation as a fundamental part of daily life. This knowledge that has given us yoga and Ayurveda, was known as Veda, hence the name Vedic. And though there are some written records, the practice has been passed down verbally from generation to generation.
Histololgy of Female Reproductive System.pptxAyeshaZaid1
Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
ABDOMINAL TRAUMA in pediatrics part one.drhasanrajab
Abdominal trauma in pediatrics refers to injuries or damage to the abdominal organs in children. It can occur due to various causes such as falls, motor vehicle accidents, sports-related injuries, and physical abuse. Children are more vulnerable to abdominal trauma due to their unique anatomical and physiological characteristics. Signs and symptoms include abdominal pain, tenderness, distension, vomiting, and signs of shock. Diagnosis involves physical examination, imaging studies, and laboratory tests. Management depends on the severity and may involve conservative treatment or surgical intervention. Prevention is crucial in reducing the incidence of abdominal trauma in children.
1. CONTENTS
INTRODUCTION.
EPIDEMIOLOGY AND ETIOLOGICAL FACTORS.
HISTORY OF DEVELOPMENT AND CLASSIFICATION.
PHARMACOKINETICS AND INNOVATION OF NEWER
AGENTS.
INTERFERENCE AND MECHANISM OF ACTION OF
ACTION ARRESTING IMMATURE CELL PROLIFERATION.
AGENTS WHICH POTENTIATE THE FUNCTION OF
CHEMOTHERAPEUTICAGENTS.
CLINICAL APPLICATION AS PRIMARY TREATMENT AND
AS ADJUVANT IN MALIGNANTLESIONS.
DRUGSENSITIVITY TO VARIOUS LESIONS AND
THERAPYREGIMES.
ROUTES OF ADMINISTRATION OF VARIOUS
CHEMOTHERAPEUTICAGENTS.
MARKERS USED TO INTERFERE WITH CELL GROWTH
TO STUDY THE PERFORMANCE OF THE DRUG.
3. INTRODUCTION
Malignancies of the head and neck region includes cancer of
the oral cavity; i.e., of the lip (International Classification of
Diseases, ninth revision (code140-ICD9:140), tongue (ICD9:141),
and other intra-oral sites (ICD9: 143-145). The salivary glands
(ICD9:142) are not normally included when describing oral
cancer, i.e., of the oropharynx (ICD9:146), nasopharynx
(ICD9:147), and hypophaynx (ICD9:148). Malignancies of these
sites are generally clubbed together as head and neck cancer, or
mouth/pharyngeal cancer, or oro-pharyngeal cancer, or sometimes
just oral cancer, because of the common etiological/risk factors
associated with these sites, with the exception of nasopharyngeal
cancers.17
The standard line of management depends on the extent of the
disease. Radiotherapy or surgery in advocated for the early lesions
and combination of both is practiced in advanced lesion.
(Vanderval1984).9
The philosophy of combining surgery and
radiotherapy in advanced lesions is that surgery fails at the
4. periphery and radiotherapy at the poorly oxygenated center of the
tumour. So combination of both help in total cure.
In search of better results, good cosmesis and better quality
of life systemic chemotherapy has been incorporated into the
treatment modalities along with surgery or radiotherapy. Systemic
chemotherapy is usually accepted as standard treatment for
palliation in patients with recurrent and metastatic head and neck
cancer who have failed the definitive therapy. Recently with the
introduction of more active chemotherapy agents and combination
systemic chemotherapy, it is being increasingly used before local
therapy in previously untreated and locally advanced head and
neck cancer. (A1 Sarraf, 1988).
Today, the role of chemotherapy in the treatment of Head and
Neck Squamous Cell Carcinoma is being intensively reevaluated.
The possibility of inducing major tumour shrinkage with
chemotherapy before local treatments has led to the enthusiastic
expectation that neoadjuvant chemotherapy could have a major
effect in improving survival rates in patients with head and neck
cancer. Conflicting data have been derived from an analysis of some
5. single-arm studies, whose results have been compared with those
obtained in historical control patients, treated with local treatment
alone. The last ten years have witnessed the changing role of
chemotherapy in patients with advanced head and neck Squamous
cell carcinomas. This is due in part to the introduction of better
agents against the disease and to the high over-all objective response
and cure rates produced by combination chemotherapy in patients
with previously untreated and advanced cancer.15
The aim of this library dissertation is to exhaustively review
the literature on chemotherapy from its historical and
developmental aspects, basic principles, its effectiveness in
improving the cure rate and also to enlighten upon the recent
advances in the field of medical oncology.
6. EPIDEMIOLOGY AND ETIOLOGICAL FACTORS
As see from Table, there is an enormous variation in the
incidence of mouth and pharyngeal cancer worldwide. The
highest, particularly those of South-East Asia. There are also,
pockets of high incidence rates in western populations, such as
that of the Bas-Rhin in France. Table 1.1 also shown that in males
the incidence of cancer – of the tongue varies from a high of 8.0 to
a low of 0.4 per 100,000; of the mouth varies from 12.4
TABLE 1.1 CANCER INCIDENCE RATES OF DIFFERENT SITES
IN THE HEAD AND NECK REGION (ICD 140-149), EXCLUDING
142 AND 147): GLOBAL VARIATION
Site of
cancer
Sex High cancer incidence Low cancer incidence
Population Rate Population Rate
Lip (140) Males Australia, South 13.5 China, Shanghai 0.1
Canada,
Newfoundland
12.7 Japan, Miyagi 0.2
Spain, Granada 12.0 India, Bangalore 0.2
Females Australia, South 3.2 China, Shanghai 0.0
Thailand, Khon Kaen 2.7 US, Puerto Rico 0.2
Israel: Jews bone in
Israel
1.6 India, Bangalore 0.2
Tongue (141) Males France, Bas-Rhin 8.0 Jaban, Yamagata 0.4
India, Bombay, 6.5 China, Tianjin 0.5
US, Connecticut:
Black
6.0 Poland, Kielce 0.8
Females India,Karunagappally, 3.7 Belarus 0.2
Philippines, Manila 2.1 Canada, New
Brunswick
0.4
US, Cooecticut: Black 1.6 China, Shangai 0.5
Mouth (143- Males France, Bas-Rhin 12.4 Peru, Lima 0.5
7. 5)
India, Trivandrum, 10.8 China, Tianjin 0.8
Italy, Trieste 8.4 Finland 1.0
Females India, Bangalore, 8.9 Spain, Zargoza 0.2
Singapore, India 3.6 Japan, Yamagata 0.3
Philippines, Manila 3.2 China, Tianjin 0.4
Oropharynx
(146)
Males France, Somme 13.3 Israel: All Jews 0.3
Slovenia, 6.7 China, Shanghai 0.3
US Connecticut:
Black
5.7 Finland 0.4
Females Switzerland, Geneva 1.6 China, Shanghai 0.1
US, SEER: Black 1.0 Belarus 0.1
Thailand, Chiang Mai 0.9 Finland 0.1
Hypopharynx Males France, Calvados, 15.0 China, Shanghai 0.1
India, Bombay 8.3 Israel: All Jews 0.2
Switzerland, Vaud 6.8 Philippines,
Manila
0.3
Females India, Madras 2.4 China, Shanghai 0.0
Switzerland, Vaud 1.0 Finland 0.1
US, Atlanta: Black 0.8 Japan, Miyagi 0.2
Notes: Numbers given are age-standardized (world) annual incidence rates per
100,000 population. Source: Parkin et al.(1997)
SEER: Surveillance, Epidemiology and End Results (Program of NCI, US).
to 0.5 per 100,000; of the oropharynx varies from 13.3 to 0.3 per
100,000; and hypopharynx varies from 15.0 to 0.1 per 100,000.
Lip cancer is particularly common in Australian and Canadian
populations with its incidence in males going up to 13.5 per
100,000. It is not so common in the South-East and East Asian
countries. For example, in Japanese, Chinese, and Indian
populations, its incidence is barely 0.2 per 100,000. The
incidence of cancer of the mouth and pharynx is universally
higher in males than in females, except in some countries of
8. South-East and East Asian countries. For example, in Japanese,
Chinese, and Indian populations, its incidence is barely 0.2 per
100,000. The incidence of cancer of the mouth and pharynx is
universally higher in males than in females, except in some
countries of South-East Asia. In Bangalore (in Indian), for
example, the incidence of cancer of the mouth (ICD9:143-145) in
males is lower, at 2.8 per 100,000, as compared to the incidence
rate of 8.9 per 100,000 in females (PArkin et al., 1997).
Globally, almost haft-a-million cancers of the mouth and
pharynx (ICD9:140-149) are diagnosed every year, and three-
fourths of these are from the developing world (Parkin et al.,
1993). A similar picture emerges as regards deaths from these
cancers. Currently, over 400,000 individuals die from this
disease every year, and again, over 80 per cent of these deaths are
from the developing world (Pisani et al., 1993).
Thus, cancer of the head and neck region is an important
cancer globally. For the developing world it is certainly of great
significance, and ranks fourth in frequency. In males, however, it
is the third most common cancer, and in females it ranks fourth
9. (Parkin et al., 1993). In countries like India, it is in fact the
leading cancer site as reported by the various cancer registries in
the country (Biennial Report, 1992). However, in western
countries also, cancer of the mouth and pharynx is now gaining
importance. There is evidence that the incidence of and mortality
rates due to this cancer has started to increase in recent decades
particularly in men (Johnson, 1991; Moller, 1989; Hakulinen et
al., 1986). Va Vacchia et al. (1997) has compared the mortality
rates of the cancer of the head and neck region (ICD9: 140-149)
at two different time periods for thirty-two European countries
and found that in males of age group 35 to 64 years the mortality
rate in the early 1990s were two-to-eight- fold higher than that
reported in the late 1950s, except in Finland. An increase in the
risk of tongue was particularly noted in young adult (Davis and
Severson, 1987; Coleman et al., 1993).
The ratios of high and low incidence rates reported world-
wide shown in Table 1.1, vary from twenty-five-fold to over a
hundred-fold. These high ratios indicate that a tremendous
potential for successful implementation of preventive strategies
10. exists, once the risk/protective factors have been identified.
These are likely to be more prevalent in males than in females in
view of the pattern of distribution of the disease in the two
sexes.17
ETIOLOGY
The association of betal quid chewing with oral cancer was
observed in India as early as 1902 by Niblock and confirmed by
Orr (1933) in an excellent epidemiologic study. Niblock (1902)
described oral cancer in Madras and Travancore and attributed it
to the habit of chewing arecanut and betel leaf and often a lime
rich paste with tobacco. Orr (1933) in his study concluded that the
use of shell lime and Vadakkan or Jaffna tobacco along with a low
vitamin content in the diet due to tapico consumption, was
primarily responsible for the prevalence of oral cancer.
Sanghvi and his colleagues (1955) demonstrated for the first
time, the association of beedi smoking in addition to chewing with
oral cancer in a case-control study at the Tata Memoriral Hospital,
Mumbai, India.
11. Besides these risk factors, diet has been implicated in the
etiology of oral cancer (Notani 1987) also alcohol usage has been
shown to be an independent risk factor (Notani 1988).9
12. CHEMOTHERAPY, HISTORY OF DEVELOPEMENT AND
CLASSIFICATION
The word ‘chemotherapy’ can be defined as the use of
chemical compounds in the treatment of infection diseases, so as
to destroy off evolving parasites or organisms without damaging
the host, tissues. The use of the term to cover all drug, or
synthetic drug, therapy needlessly removes a distinction which is
convenient to the clinician and has the sanction of long usage. By
convention the term is used to include therapy of cancer.11
This method of treating cancer has been used in head and
neck tumours for palliation and in a curative role, both as integral
part of a planned regime involving surgery or radiotherapy or
both, and on its own. Certain tumors have been found to respond
well to chemotherapy and in management of these it is an
accepted part of total treatment. In the context of head and neck
malignancies how ever such tumours are rarities and it is the
value of chemotherapy in the common tumours such as squamous
carcinoma and the salivary tumours which is of real interest to the
oral and maxillofacial surgeon.18
13. History of drug Discovery
Chemotherapy has its origin in the work of Paul Ehrilich who
coined the term in reference to the systemic treatment of both
infection diseases and neoplasia. Many of the Ehrlich’s concepts
regarding the experimental evaluation of new therapies using
murine or rat models have survived to the present day and have
provided a number of important biologic insights that have been
applied successfully to the clinical setting. Gilman and Philips
conducted the first clinical trial of nitrogen mustard in patients
with malignant lymphomas at Yale university in 1947. The
results, initially published in 1946, could be said to mark the
beginning of modern chemotherapy.13
HISTORICAL OUTLINE OF DEVELOPMENT OF
CANCER CHEMOTHERAPY
A. Period 1946-1960
14. - Development of single-drug chemotherapy mainly on
empirical basis.
- Establishment of critical criteria for the clinical
development of new drugs: criteria of response; toxicity;
performance status; optimum tolerated dose.
- First results from the treatment of leukemias and
malignant lymphomas. Generally poor results in the
treatment of advanced solid tumours.
B. PERIOD 1960-1970
- Development of knowledge of cell kinetics and
application of kinetic concepts to the design of
chemotherapy schedules.
- Broadening of the experimental basis for clinical
chemotherapy.
- Introduction of pharmacokinetic concepts into clinical
chemotherapy.
- First developments in the field of combination
chemotherapy.
15. - Introduction of the concept of the controlled randomized
clinical trials into clinical chemotherapy assessment.
- Further improvement of treatment results in leukemias
and lymphomas and significant progress in the results
obtained in the treatment of certain solid tumours.
C. PERIOD 1970 TILL DATE
- Development of the concept of the combined modality
approach; improved cooperation between the onco-
surgeon, radiotherapist and chemotherapist.
- First indication of definitive role for adjuvant
chemotherapy.
- Recognition, in long-term survivors, of the late toxicities
of anti-cancer drugs particularly when combined with
radiotherapy.
- Development of the concepts of immunotherapy in man.
Disappointing results despite widespread application.14
16. Classification of chemotherapeutic agents 3
Major Classes Examples Malignancies Used
in
Toxicities
1.Alkylating
agents
Nitrogen
mustard
Chlorambucil
Ifosfamide
Melphalan
Thiotepa
Cisplatin
Carboplatin
Lymphomas
Chronic
lymphoblastic
leukemia
Sarcomas
Myeloma
Breast cancer
Ovarian cancer
Head and neck cancer
Leucopenia
Anemia
Thrombocytopenia
Nausea and
vomiting
Neurotoxicity
Alopecia
II.Antimetabolites Methotrexate
5-Fluorouracil
Ara-C
Hydroxyurea
Fludarabine
Breast and
gastrointestinal
cancer
Acute myeloblastic
leukemia
Chriocarcinoma
Genitourinary cancer
Head and neck cancer
Lymphoma
Mucositis
Diarrhea
Leucopenia
Anemia
Thrombocytopenia
Alopecia
III. Antibiotics Actinomycin-D
Doxorubin
(Adriamycin)
Daunorubicin
Mithramycin
Mitomycin
Bleomycin
Mitoxantrone
Acute myeloblastic
leukemia
Germ cell cancer
Gastrointestinal, lung,
Breast cancer
Head and neck
cancers
Sarcomas
Lymphoma
Leucopenia,
anemia, and
thrombocytopenia
Mucositis
Diarrhea
Skin disturbances
Alopecia
Nausea and
vomiting
Cardiac and
pulmonary toxicity
IV. Plant alkaloids Vincristine
Vinblastine
VP-16
Taxol
Testicular, lung,
breast and bladder
cancers
Lymphoma
Leukopenia
Anemia
Thrombocytopenia
Alopecia
Nausea
V.Micellaneous DTIC
M-AMSA
Sarcomas
Acute myeloblastic
Leucopenia
Anemia
18. PHARMACOKINETICS AND INNOVATION OF NEWER
AGENTS
Pharmacokinetic of cancer chemotherapy
Because there are such narrow margins between effective
and toxic dosages for many antineoplastic agents, rational therapy
should be assisted by the ability to maintain drug concentrations
in specified therapeutic ranges. Thorough pharmacokinetic
analyses have been performed for a number of anticancer drugs in
a variety of clinical situations.
Modeling
The classical pharmacokinetic device for describing the
disappearance of drugs from plasma is the two-compartment open
model. The concept assumes that a drug is instantaneously
injected and distributed in Compartment 1(with concentration, C1,
and volume, V1) and that all elimination of the drug from the
system occurs from this “central” compartment. Immediately
after injection the drug may distribute into compartment
2(concentration, C2, and volume, V2) at a rate defined by k12.
Drug may move from Compartment 2 (the “peripheral”
19. compartment) at the rate k21 into the central compartment, thence
to be eliminated. The elimination rate is indicated as kel.
Movement of drug into and out of either compartment is a first-
order process and the rate constants k12, k21, and kel have
dimensions of inverse time (e.g., min-1
, hr-1
). A typical two-
compartmental curve for plasma disappearance of a drug is
depicted in fig which plots concentrations on a logarithmic
ordinate and time on a linear abscissa. This smooth curve can be
divided into two discrete exponential terms. Ae-at
and Be-βt
,
indicated by hatched lines. The concentration, C, at any time is
the sum of these terms. Dividing the curve allows for definition
of the earlier portion as the distribution phase of drug disposition,
and of the later portion as the elimination phase. Five parameters
are commonly found in pharmacokinetic descriptions of
antineoplastic agents, and can be calculated from the relationship,
C= Aeot
+ Be-β
. The concentration at the moment of injection, C0,
is usually the peak concentration during rapid intravenous bolus
injections and equals the sum of the constants A and B: C0 =
A+B. The terminal elimination half life, t1/2, is determined by the
20. elimination rate constants, β: t1/2 = 0.693/β. The initial volue of
distribution of the drug, Vd, is related to the initial (peak)
concentration, Co, and the dose given: dose = Vd x Co, or Vd =
dose/Do (dimensional units of dose and Co must be similar, e.g.,
mg and mg/ml or nmol and nmol/ml). The area under the plasma
concentration-time plot provides a measures of the exposure of the
body or of a particular tissue to a drug over a period of time. This
quantity, often referred to as the area under curve (AUC) or
concentration x time product (C x t) of a drug, is calculated by
integrating the equation C = Ae-nt
+ Be-β
. Because e-t
approaches
zero at very late times of observation, this integral can be reduced
to C x t (or AUC)=A/α + B/β. The C x t can be estimated equally
well by the trapezoidal rule. Finally, the clearance of a drug Cl
=kel x V1. In practice kel and V1 are difficult to determine and
clearance values can be estimated as Cl = β x Vd.2
21.
22. New Chemotherapy Agents
To date, the combination of cisplatin and 5-FU represents
standard polychemotherapy in association with RT in HN
cancers.5
Recently, pre-clinical studies have demonstrated an
enhanced activity of RT with new cytotoxic agents such as taxol,
which has radiosensitizing properties and anti-cancer activity. A
phase I study was conducted with 24-hours paclitaxel infusion
and simultaneous RT in locally advanced, recurrent metastatic
Head andNeck malignancies. The dose limiting toxicity was
febrile granulocytopenia and the maximum tolerated dose of
paclitaxel was 75 mg/m2
. All the patients with locally advanced
disease demonstrated either a complete or a partial response, and
at a median follow-up of more than 1 year only 9 per cent of
patients had progressed (Seinberg et al., 1977). The results were
confirmed by an additional preliminary report in a study using
concurrently taxol at 60 mg/70 per cent showing complete
response. Mucositis was the main toxicity (Amrein et al., 1998).
23. A potentially synergistic activity between RT and gemicitabine
has been suggested in recent trials. A pilot study performed at the
Institute of Cancer Research, Genoa, Italy and Croce General
Hospital, Cuneo, Italy demonstrated a high response rate (90 per
cent) in advanced, inoperable Head and Neck cancer patients,
treated with alternating RT and a combination of gemcitabine and
cisplatin (Benasso et al., 1997; 1998). A complete response was
observed in 85 per cent of the patients, of which more than 70 per
cent are alive and disease-free after a median follow-up of 1 year.
However, modifications to the schedule are mandatory in light of
the heavy toxicity observed, but the high anti-tumour activity
obtained suggests further investigations on the combination of RT
and gemcitabine.17
INTERFERENCE AND MECHANISM OF ACTION
ARRESTING IMMATURE CELL PROLIFERATION
24. General
Chemotherapy is planned on the basis of observed
differences between normal and tumour cells in response to anti-
tumour agents used both as single and in combination. Part of the
difference between normal and neoplastic cells can be emphasized
that cell kinetics cannot explain all the consequences of tumour-
cell exposure to a drug, since these are also dependent upon
pharmacokinetics, biochemistry and tumour biology.
The proliferation of tumour cells is not entirely autonomous,
neither is it constant; it varies with the size of the tumour and is
related to its blood supply. Animal studies show that the
characteristics of tumour cell proliferation have an important
influence on the response to chemotherapy. Skipper (1971) has
reviewed some of the principles concerned and the following
generalizations can be made for experimental tumours.14
|
The Cell Cycle
25. An understanding of cell-cycle kinetics is essential for the
proper use of the current generation of antineoplastic agents.
Many of the most potent cytotoxic agents act at specific phases of
the cell cycle and, therefore, have activity only against cells that
are in the process of division. Accordingly, human neoplasms
that are currently most susceptible to chemotherapeutic measure
are those with a large growth fraction, that is, a high percentage
of cells in the process of division. Similarly, normal tissues that
proliferate rapidly (bone marrow, hair follicles, and intestinal
epithelium) are subject to damage by some of these potent
antineoplastic drugs, and such toxicity often limits the usefulness
of drugs. On the other hand, slow –growing tumors with a small
growth fraction (for example, carcinomas of the colon or lung)
are often unresponsive to cytotoxic drugs. Although difference in
the duration of the cell cycle occur between cells of various types,
all cells display a similar pattern during the division process.
This cellcycle may be characterized as follows : (1) there is a
presynthetic phase (G1); (2) the synthesis of DNA occurs (S); (3)
an interval follows the termination of DNA synthesis, the
26. postsynthetic phase (G2); and (4) mitosis (M) ensues – the G2 cell,
containing a double complement of DNA, divides into two
daughter G1 cells. Each of theses cells may immediately reenter
the cell cycle or pass into a nonproliferative stage, referred to as
G0. The cells of certain specialized tissues may differentiate into
functional cells that are no longer capable of division. On the
other hand, many cells, especially those in slow-growing tumors,
may remain in the G0 state for prolonged periods, only to be
recruited into the division cycle again at a much later time. Most
antineoplastic agents act specifically on processes such as the
synthesis of DNA or of the mitotic spindle. Other block the
synthesis of DNA precursors or damage the integrity of DNA.
While most of the known anticancer drugs are G1 is the period
between mitosis and the beginning of DNA synthesis. Resting
cells (cells that are not preparing for cell division) are said to be
in subphase of G1, G0. S is the period of DNA synthesis; G2 the
premitotic interval; and M the period of mitosis. Example of cell-
cycle-dependent anticancer drugs are listed in blue below the
phase in which they act. Drugs that are cytotoxic for cells at any
27. point in the cycle are called cycle – phase-nonspecific drugs.
(Modified from Pratt et al., 1994 with permission.) most effective
against actively proliferating cells, some (called – cell cycle
phase-specific, such as cytosine arabinoside and methotrexate)
affect cells only during the S phase or during mitosis (e.g.,
pactiaxel and vinca alkalids) and will not kill nondividing cells.
Damaged cells that cross the G1/S boundary will undergo
apoptosis, or programmed cells death, if the p53 gene is intact
and exerts its normal checkpoint function. If the p53 gene is
mutated and the diversion down the apoptotic pathway does not
take place, the damaged and potentially mutated cells will
proceed through S phase and emerge as a drug-resistant
population.8
All tissues are basically composed of three populations of
cells. The first of these consist of cells that are continuously
traversing the cell cycle. The second population is composed of
cells that leave the cell cycle after a certain number of divisions to
differentiate and later never to divide again, and die. In the third
population group, the cells remain dormant and leave the cell
28. cycle temporarily to return when a stimulus or other
environmental conditions dictates their re-entry into the cell cycle.
An example of these populations is seen in the bone marrow. The
marrow is composed of a sub-set of cells which are continuously
traversing the cell cycle by dividing and producing more blast
cells from precursors.
The second population consists of cells such as granulocytes
which have differentiated and are destined to perform a specific
29. function, not undergo further mitosis, and finally to die. Cells in
the third population include stem cells which do not cycle until
marrow depletion causes them to re-enter the cell cycle and
proliferate again.
In terms of tissue growth in both normal and abnormal
situations, 3 factors regulate the population: 1. The cell cycle and
its duration, 2. The growth fraction, 3. The rate of cell loss. The
cell cycle time refers to the interval between mitoses. The faster
that the cell cycles, the faster the increase in the total number of
cells. The growth fraction refers to the subset of the population of
cells which are actually traversing the cell cycle. The larger the
number of cycling cells, the more cells will be produced. The rate
of cell loss refers to the number of cells that die or leave the cell
loss population by migrating to other tissue. In an adult organism
where growth has ceased to exist, there is a steady state produced
where cell loss is equal to cell production. Growth of both normal
and neoplastic tissue occurs as a results of an increase in the total
cell number.1
30. Host-Tumor-Drug Relationship and the response to
Chemotherapy. A number of pharmacokinetic parameters such as
activation, inactivation, binding to carrier proteins, excretion, and
delivery of drug have obvious impact in the clinical response to
even the most active agents. As well, the response to an agent
given in an appropriate schedule seems to depend heavily on the
proliferative status of tumor cell populations, which in turn seems
to vary as a function of tumor burden. Thus, understanding the
host-tumor relationship with the purpose of designing more
effective schedules might be profitable.
The early pioneering work of Skipper et al in the L1210
leukemia model led to their statement of the log-kill hypothesis in
1964. This holds that a constant fraction of the tumor cells will
survive a given level of effective therapy irrespective to the size of
the tumor. Thus, the greatest number of cells will be killed in large
tumors, while small tumors should be curable if the same level of
therapy is repeatedly applied until virtually every cell is killed.
In 1977 Norton and Simon suggested that tumor killing for a
given level of effective therapy varies with the growth rate of the
31. tumor. For L1210 or other tumors which follow logarithmic
growth, growth fraction (GF) is large and stays constant. Thus,
growth rate accelerates as the tumor grows, rendering large tumors
sensitive. In contrast, for Gompertzian tumor growth, which
probably more accurately describes human tumors, GF is large
initially, but progressively diminishes. Growth rate progressively
increases reaching its maximum at about 37% of total volume and
subsequently decreases, as decreased GF become significant.
Consequently, large tumors, as well as very small tumors, have
low growth rates wand are relatively resistant to effective
treatment.16
- The doubling time of a tumour increases with the
tumour mass up to a critical point while the thymidine
labeling index decreases. The growth of most
experimental tumours can be described as Gompertzian
(after the statistician who first described the
mathematics) rather than linear.
32. - The response to chemotherapy is reflected by the change
in the thymidine-labelling index (the number of cells
synthesizing DNA).
- The shorter the doubling time at the onset of treatment,
the better the initial response to chemotherapy is likely to
be.
- As the tumour volume increases the disease becomes less
easy to eradicate by single modality therapy.
- Non-phase dependent agents are theoretically more
effective than phase-dependent agents against tumours
with long times and low thymidine-labelling indices.
Gompertzian growth curve
33. Animal tumours do not grow in a linear manner. As they
become larger the growth rate slow. Though few data are
available for human tumours, there are suggestions that the above
generalizations may apply to human cancer, and proliferation
studies may come to be helpful in the choice of chemotherapy and
in predicting duration of remission and survival.
Phase-specificity / Phase dependency of cytotoxic drugs
Phase dependent agents exert an increasingly toxic effect
with prolonged exposure of the cells to an effective concentration
while in the sensitive phase. This results from an accumulation of
cells in that phase (provided the drug does not prevent entry).
Given over a short period, even at high dose level, these agents are
not very toxic. Cells not in the sensitive phase, at the time of the
brief exposure, will be minimally affected.
The toxicity of cycle-dependent or non-phase-dependent
drugs for both malignant and normal cells depends on the drug
34. concentration and the duration of exposure. To achieve maximum
effect it is therefore logical to administer the drugs intermittently
at the highest dose. Some drugs interfere with progression from
one phase of the cell cycle to another. Cytosine arabinoside and
hydroxyurea, for example, inhibit the progression of G1 cells into
S and therefore cells not is S are protected. This protective effect
can be overcome by giving the drug intermittently at intervals that
permit the non-S phase cells to enter S during the drug-free
period.
Diagrammatic presentation of the phase specificity of some of
the cytotoxic drugs
35. Relationship between cell kill dosage of cytotoxic agent
(Clarysse, Kenis and Mathe, 1976)
A. Drugs that kill cells
exponentially with increasing
dosage
B. Drugs that kill
exponentially at lower dosages
but reach a plateau at higher
doses
R = Rapidly proliferating cells
S = Slowly proliferating cells
36. Note that for both A and B rapidly proliferating cells are more
sensitive than slowly proliferating cells
Classification of anti-tumour agents according to their effect
on the cell cycle
Predominantly non-phase
dependent
Predominantly phase-
dependent
Alkylating agents Vinca alkaloids
Nitrosoureas Hydroxyurea
Anthracyclines Cytosine arabinoside
Imidazole carboxamide (DTIC) Methotrexate
Mitomycin C 6-Mercaptopurine
Actinomycin D 6-Thioguanine
Procarbazine
Podophyllotoxins - VM26
- VPP 16-213
37. Drug metabolism
Most anti-cancer agents are metabolized in the body, usually
to products which are inactive having lower lipid solubility. These
are then excreted. In some instances, active metabolites are
produced (e.g. cyclophosphamide).
Drug absorption, distribution and excretion
Anabolic activation is particularly important in the case of
anti-metabolites. The role of anabolic and catabolic activation and
deactivation is of great importance since it may form the basis of
selective activity in different cell types (normal and malignant).
Usually, drug metabolism occurs in two phases:
EXCRETION
Renal and extra-renal
Biotransformation to
active or inactive
product(s)
Free drug in plasma
ABSORPTION
Plasma protein binding
Tissue binding (specific
and non-specific)
tumour and normal
tissues
38. A. Biotransformation – involving hydroxylation,
oxidation, reduction or hydrolysis
B. Conjugation – e.g. with sulphate, acetyl or a
glucuronyl group.
Drug metabolism occurs chiefly in the liver but may also
take place in the plasma, gastro-intestinal tract, kidneys and lungs.
For this reason, hepatic function is an important consideration in
the choice of dose of some anti-tumor agents. The anthracyclines
(e.g. Adriamycin and Daunorubicin) are excreted mainly in the
bile and these drugs produce enhanced toxicity in patients with
hepatic failure or biliary obstruction.
EXCRETION
Most anti-tumour agents are excreted in the bile and urine.
Drugs not bound to albumin are filtered by the glomerulus. The
proximal tubule possesses two pump systems which transport
drugs from plasma to urine, one for the secretary mechanism and
probenecid can be used to reduce the elimination of acidic drugs
(e.g. penicillins and, possibly, anti-cancer agents such as
39. Methotrexate). Passive reabsorption of lipid-soluble drugs and the
non-ionized fraction of drugs which are weak electrolytes takes
place in the renal tubule. Elimination of weak acids by the kidney
is increased by alkalinizing the urine. The reverse is true for weak
bases. Active tubular reabsorption of ions and various solutes can
also take place in the proximal tubule.
Excretion in tears, sweat, saliva and in the breath is
relatively unimportant but may be the cause of unusual toxicity
such as the conjunctivitis seen following the use of high dose
Methotrexate. Several host dependent factors have important
influences on drug absorption, distribution, metabolism and
excretion. Illness which affects renal and hepatic function, bone-
marrow reserve or gastro-intestinal function may well have a
marked influence on the efficacy and toxicity of a drug.
Methotrexate, for example, is largely excreted in the urine and its
toxicity may be markedly enhanced in patients with renal failure.14
40. AGENT WHICH PONTENTIATE THE FUNCTION OF
CHEMOTHERAPEUTIC AGENTS
Chemosensitization
Hypoxic cell Chemosensitizers
In the animal model the hypoxic cell sensitizers
misonidazole and SR-2508 enhance of the cytotoxicities of
alkylating agents and nitrosoureas. However, the optimal method
of administration is not known. Dose-response curves for the
different sensitizers and alkylating agents are needed to optimize
efficacy and reduce toxicity. A randomized trial using
intravenous melphalan with or without misonidazole in
metastiatic non-small-cell lung cancer showed a small, but
statistically significant, improvement in response rate with
misonidazole. Other single-arm trials of misonidazole and
alkylating agents have been negative or inconclusive.
Perfluorochemicals as Chemosensitizers
Fluosol-DA and carbogen breathing increased the antitumor
efficacy of bleomycin and cyclophophamide in the animal model.
With cyclophosphamide when the Fluosol dose was increased
41. from 0.1 to 0.3 ml and carbogen breathing extended from 6 hr the
tumor growth delay tripled. Similar effects were seen with
bleomycin.
Chemosensitization by Vasocative Drugs
Several vasoactive drungs can selectively reduced blood
flow and increases the percent of hypoxic areas in experimental
tumor systems. By promoting hypoxia in the tumor, the
cytotoxicity of drugs which are active in hypoxic conditions is
potentiated. When hydralazine was given prior to or after the
alkylating agents melphalan, melphaln’s antitumour activity
increased by a factor of 2 and 3, respectively. However, systemic
toxicity was only increased by a factor of 1.2. Additional animal
studies have shown that hydralazine cause a dose-dependent
decrease in tumour energy metabolism (measured by PNMR
spectroscopy). PH, and perfusion pressure in tumors. Despite
these alternations in tumor metabolism, toxicity is minimal in the
treated animals. These data suggest that hydralazine might be
beneficial combined with therapy which is specifically toxic by
hypoxic cells (e.g., hyperthermia, mitomycin C, and perhaps after
42. alkylting agents). Verapamil and other calcium chemotherapeutic
agents also potentiate the efficacy of certain chemotherapeutic
agents by preventing drug efflux and altering tumor blood flow .
Agents That Are Toxic to Hypoxic Cells
The bioreductive alkylating agents mitomycin and
porfiromycin may target to hypoxic cells. In a randomized trial
of radiation with or without mitomycin in head and neck cancer,
improved disease-free survival was observed in the patients
treated with mitomycin .
SR-4233 is a new benzotriazine which is 15-to 50-fold more
toxic to anoxic than to well-oxygenated human tumor cells in
vitro. However, the invivo results with SR-4233 were less
impressive.
A new analog, SR-4482 is more toxic than SR-4233 in vitro,
and less toxic in vivo.Several important effects of the
nitroimidazole compounds (hypoxic cytotoxicity, thiol depletion,
and chemosensitization) are felt to be due to reduction of the
parent compound. The benzotriazines are activated by enzymatic
reduction. The differential activity of various reductases in
43. normal and malignant tissues may lead to the logical selection of
the appropriate sensitizer in this class.
NONHYPOXIC RADIATION SENTIZIERS
Halogenated pyrimidines
Bromodeoxyuridine (BUdR) and iododeoxyuridine (IUdR),
are halogenated pyrimidines, which were designed as thymidine
analogs. The initial hypothesis was that these drugs could be
incorporated into the DNA of actively dividing cells and act as
radiosensitizers. Clinical trails should attempt to achieve
sustained plasma levels of 10µm IUdR for optimal
radiosensitization.
Early clinical trials using the halogenated pyrimidines
demonstrated excessive normal tissue reactions without increased
antitumor efficacy in patients with head and neck cancer. Since
the halogenated pyrimidines are absorbed preferentially in
actively dividing cells, it is not surprising that severe mucosal
toxicity was encountered. Since BUdR is associated with
photosensitivity, recent interest has focused on IUdR. More
encouraging results may be observed in the Phase II trials
44. combining halogenated pyrimidine with radiotherapy for gliomas
and sarcomas, since the irradiated, surrounding normal tissues
have lower mitotic rates .
Two clinical studies of continuous intrahepatic artery
infusions of IUdR have shown that human colon cancer cells
absorb almost six times the amount of IUdR compared with
adjacent normal liver. Regional infusion also decreases systemic
IUdR leves 50-78% .
DNA repair inhibitors
Inhibitors of DNA repair may act as radiosensitizers.
Inhibitors of DNA replications which act by inhibiting DNA-
dependent DNA polymerases can decrease the radiation damage
at the chromosome level. However, the effectiveness of
inhibiting both replication and repair of DNA does not always
correlate with clinical response. In human cervical cancer cell
lines, the DNA repair inhibitors reduced radiation survival.
Various DNA repair inhibitors have been studies in the
laboratory. Hydroxyurea reduced survival at both high and low
45. radiation doses. Beta-ARA-A and caffeine are more effective in
reducing all survival at low doses.
Nicotinamide
In several animal models nicotinamide has bee shown to
preferentially radiosensitize tumors, perhaps by reducing
hypoxia. The radiation enhancement ratio ranged from 1.2 to 1.7
in animal tumors and 1/0 to 1.3 in normal tissues.
Platinum analog
Cis-plantinum is one of the most active chemotherapeutic
agents. However, its radiosensitizing properties have not been
exploited with fractionated radiation because cis-plantinum’s
normal tissue toxicity. The less toxic transiomer trans-platinum
and other platinum analogs interact with radition in vitro. Trans-
platinum might be an ideal sensitizer for most radiation
fractionation schedules used in clinical practice.
Thiol Depletors
As the thiol content in cells increases, most cells are
protected from the cytotoxicity of radition of alkylting agents. In
vitro, thiol depletion leads to radiosensitization. When BSO
46. depletes cellular glutathione in vitro, radiation injury increases.
However, the presence of other reducing agents (such as ascorbic
acid or α-tocophero) blunts the sentizing effect of BSO in vivo.
Lowering glutathione levels in tumours might potentiate the
effect of hypoxic radiosensitizers. However, glutathione
depletion’s major likely role will be in chemosensitization.4
Chemoprevention
The most effective methods of preventing oral cancer are
avoidance of the major etiological factors, tobacco and alcohol.
However patients with premalignant conditions in the mouth have
a high risk of developing carcinoma, and patients successfully
treated for oral cancer have a high risk of developing seconds
primary neoplasms. Accordingly there is now a considerable
interest in measures to prevent the development of cancer in this
high risk group, including the use of chemical agents.
Retinoids
Vitamin A and related compounds have several properties
which suggests that they may be useful as chemopreventive
agents in oral squamous cell carcinoma. They are modulators of
47. epithelial cell differentiation, both in vitro and in vivo. They
probably act by regulating gene expression. Cell nuclei contain
retinoic acid receptors that mediate the biological effects of
retinoids. The ligand for these receptors is probably all-trans-
retinoic acid, to which retinoids must be metabolized to exert
their biological effect. In experimental animals vitamin A
deficiency causes squamous metaplasia similar to that induced by
chemical carcinogens. It has been found that vitamin A and
related retinoids can reverse the metaplsia in vitamin A deficient
animals. They have also been shown to inhibit the growth of
squamous carcinoma cell lines in vitro.
There have been several studies of treatment of oral
dysplastic leukoplakia by retinoids. Hong et al. used isotretinoin
in a dose of 1-2 mg/kg per day for 3 months in a placebo-
controlled trail involving 44 patients. The drug produced major
clinical responses in 67 per cent of patients compared with 10 per
cent who received placebo (P=0.0002) and reversed the dysplastic
change in 56 per cent. At this dosage isotretinoin has appreciable
toxicity, with peeling of the skin, chelitis, facial erythema and
48. hypertriglyceridaemia in about 75 percent of patients, headaches
and dyspepsia also occasionally occur. The leukoplakic changes
recur after stopping treatment. However a subsequent study
demonstrated that low dose maintenance treatment (0.5 mg/kg)
after the end of the 3 months of high dose therapy was well
tolerated and prevented recurrences.
Vitamin A in high dosage was shown to reverse
premalignant change in Indian betel chewers. Vitamin A is
generally less loxic than isotretinoin, but effective dose levels,
i.e.300 000 IU per day, produce similar if less severe side effects.
In both of the above studies β-carotene was also tested as
maintenance treatment because of its lower either vitamin A or
isotretinoin, probably because it is less easily metabolised to the
active ligand.
Experience with isotretinoin in the treatment of leukoplakia
has led to being tested as adjuvant treatment in patients with oral
and laryngeal carcinoma who were disease-free after primary
treatment. There was no influence on recurrence rates of the
original tumours, but there was a significant reduction in the
49. incidence of second primary tumours. This experience led to the
setting up of larger multicentre chemopreventive trails in cured
head and neck cancer patients, for examples the Euroscan trail
using vitamin A.
Antioxidants
Agents with antioxidant properties can inhibit the effects of
many toxins including carcinogens. N-acetylcysteine, a precursor
of intracellular glutathione, inhibits the mutagenic effect of
carcinogens such as benzpvrene in vitro.10
50. CLINICAL APPLICATION AS PRIMARY
TREATMENT AND AS ADJUVANT IN
MALIGNANT LESIONS
One of the most important factors in selecting
chemotherapy is the incidence of clinical and histological cure
rate achieved by such treatment. Present chemotherapy regimes do
not produce cure rate in all patients treated and considerable
improvement is required in this area. Also, it is very important to
mention that after clinical cure rate is achieved, the additional
number of courses of chemotherapy administered is critical in
determining the frequency of histological cure rate and duration of
overall survival. A clinical cure rate occurring after one course of
chemotherapy, when additional courses of the same chemotherapy
are planned, is a more favorable prognostic factor than clinical
cure rate occurring at the end of the last planned course of
chemotherapy. It is important in evaluating chemotherapy as part
of multimodality treatment that in addition to the minimum
number of courses needed to achieve clinical cure rate.
51. The goals of including chemotherapy as part of the
multimodality treatment in patients with locally advanced head
and neck cancers are better overall survival and/or quality of life.
When our best chemotherapy is proven to be of value as part of
multimodality therapy, then the possibility of delaying or
performing less extensive surgery can be studied. The main
purpose would be to lessen the cosmetic and/or functional
morbidity caused by radical surgical procedures without
jeopardizing the survival of the patients.
Induction (initial) chemotherapy
To investigate the effectiveness of chemotherapy as part of
multimodality treatment, the drugs must be administered before
definitive surgery and/or radiotherapy when gross and measurable
disease in present. As with most new therapies patients with more
advanced disease (stage III and IV) are usually selected for trials.
The use of chemotherapy as initial treatment started in the
mid 1970s because of the increased local toxicities of
simultaneously administered chemotherapy and radiotherapy and
lack of benefit of the combined approach at that time.
52. Initially high dose methotrexate with leucovorin rescue as
utilized. In general, the overall response rate to this agent alone in
previously untreated patients with locally advanced disease was
poor, with no clinical cure rate and no evidence of improved
survival of these patients as compared with historical controls.
With the demonstration that cisplatin was effective as a
single agent in patients with recurrent cancer of the head and neck,
many trails were initiated with cisplatin containing combinations
in patients with previously untreated and locally advanced disease,
summarizes the overall results of trials with cisplatin alone or in
combination with other agent(s) that are known to be effective
against head and neck cancers. More than sixty such trials were
reported up to 1985. All except two trials were single arm pilot
studies.
Because of patient heterogeneity and marked variation in the
doses and schedules of drug administration it is difficult to draw
conclusions. It does seem that cisplain combinations are superior
to cisplatin alone in achieving clinical cure rate and in overall
response rate. The most common agent(s) combined with cisplatin
53. are bleomycin alone or with other agents like methotrexate,
vinblastine or Oncovin. The overall clinical cure rate rate seems
high with cisplatin and 5-FU infusion than with any of the
cisplatin and bleomycin combinations. Also, the incidence of
histological cure rate in those clinical cure rate patients who
underwent surgical resection is high after cisplatin and 5-FU
infusion than with any cisplatin and bleomycin combinations. The
side effects of these combinations are acceptable and reversible.
From the clinical trails, patients achieving clinical cure rate
to the initial chemotherapy had significantly superior survival than
those patients with less than cure rate to the treatment regardless
of the subsequent definitive therapy. More important those cure
rate patients who were found to have no histological disease after
surgical resection have statistically superior survival when
compared with those clinical cure rate patients who had residual
disease at surgery.
Oral cancers constitute about 10% and 6% of all cancer
cases in males and females respectively in India (ICMR 1989).
Carcinoma of buccal mucosa is more commonly seen among
54. females than males with a 3:1 incidence. About 80% of these
tumors are locally advanced (Stage III and IV) at the time of
presentation, inspite of oral cavity being easily accessible for
examination and early identification.
Buccal mucosa is made up of stratified squamous
epithelium covering the internal surface of lips and cheeks.
Pathologically buccal mucosal cancers vary from verruccous
exophytic indolent types with well demarcated borders to deeply
infiltrating ulcerative painful tumor with poorly defined margins.
More than 90% of these tumors are squamous cell carcinomas and
the remaining make up for minor salivary gland tumors,
melanoma, sarcoma etc., (Strong and Spiro 1987). Million and
Cassissi (1984) reported that 95% of oral cancers were squamous
cell carcinomas.
The standard line of management of buccal mucosa cancer
depends on the extent of the disease. Radiotherapy or surgery is
advocated for early lesions (Stage I & II) and combination of both
practiced in advanced lesions (Stage III & IV) (Vanderwaal 1984).
The philosophy of combining surgery and radiotherapy in
55. advanced lesions is that surgery fails at the periphery and
radiotherapy at the poorly oxygenated center of the tumor.
As seen earlier, majority of the patients present with
advanced lesions and even combination of surgery and
radiotherapy may not be possible in most of the patients, as the
tumors either will be unresectable or the patient will not be fit to
undergo surgery due to associated medical conditions.
Over the years the results with surgery and radiotherapy has
not improved much and has reached a plateau (RTOG, 1980,
Perez). The locoregional recurrence with the above modality is as
high as 60% (Vikram, 1984; Kramer, 1985). The combined
modality of surgery and radiotherapy in advanced cases has given
better results only when surgery was very extensive and
cosmetically inacceptable (Pinsolle, 1992).
In search of better results, good cosmesis and better quality
of life systemic chemotherapy has been incorporated into the
treatment modalities along with surgery or radiotherapy. Systemic
chemotherapy is usually accepted as standard treatment for
palliation in patients with recurrent and metastatic head and neck
56. cancers who have failed the definitive therapy. Recently with
introduction of more active chemotherapy agents and combination
systemic chemotherapy is being increasingly used before local
therapy in previously untreated and locally advanced head and
neck cancers (Al Sarraf 1988).
Systemic chemotherapy has been used in various forms as
detailed below.
Induction chemotherapy: This is other wise called as
neoadjuvant chemotherapy. This started being used from mid
1970’s because of increased local toxicities seen with
simultaneously administered chemotherapy and radiotherapy and
lack of benefit of combined approach during 1960’s (Al Sarraf
1988). The drugs are administered prior to start of definitive
therapy. The rational for neoadjuvant chemotherapy is that a)
ability to deliver drug to untreated tumors with intact vascularity,
b) Better tolerance to chemotherapy, c) to enhance the efficacy of
planned definitive local therapy after cytoreduction and
eradication of sub clinical metastasis and d) for better overall
survival and quality of life.
57. Concurrent chemotherapy: The drugs are used
simultaneously with definitive therapy (Radio Therapy or Surgery).
Chemotherapy after surgery and before radiotherapy
(“Sandwich”)
Sandwich method: Here chemotherapy is administered
after surgery and before delivering radiotherapy.
Various agents have been used either singly or in
combination as chemotherapy. The agents used are Methotrexate,
bleomycin, 5-flurouracil (5-Fu), vinblastine and cisplatinum. The
commonly used combinations being methotrexate and
5-Fluorouracil (Tarpley 1975; Al Sarraf 197; Alan Coates 1984;
Ervin 1987; Jaulerry 1991) and Cisplatinum and 5-Fluorouracil
(Singhal 1993). Ten years of clinical trails have not yet identified
the best chemotherapy regimen to be combined with definitive
treatment (Al Sarraf 1988). Methotreaxate and –Fluorouracil has
been used in combination in advanced head and neck cancers as
neoadjuvant chemotherapy agents (Alan Coats 1984; Jacobs 1982;
Pitman 1983; Mackintosh 1988) with varying success.
Oral cancers are common tumors presenting in advanced
stages. The effect of treatment is easily assessable in oral cancers.
Neoadjuvant chemotherapy has shown its effectiveness in head
and neck cases. So we want to assess the effect of combined
58. neoadjuvant chemotherapy with definitive radiotherapy in
carcinoma of buccal mucosa.
In patients with previously untreated respectable and
operable, locally advanced head and neck cancer, the timing and
sequence of effective chemotherapy as part of multimodality
treatment is important and needs to be investigated. The following
problems existed with induction chemotherapy when given as the
initial treatment in combined modality therapy:
1. Patients refuse surgical resection or any further
therapy, especially those achieving the best
response to chemotherapy.
2. The planned surgery after initial successful
chemotherapy is not the same as that done in
previously untreated patients with identical tumors.
3. The results of surgery after three courses of
chemotherapy, even with achievement of up to a
50% clinical cure rate, are no different than
adequate surgery without preoperative treatment.
4. Chemotherapy yields higher objective response
rates in patients with smaller tumor masses (stage
III v stage IV). Thus a higher effectiveness is
expected of the same chemotherapy when it is
given to patients with minimal residual disease
59. after surgery (microscopic) rather than gross bulky
disease present before surgery.
Because of the above, a pilot study for patients with locally
advanced but respectable cancer in which three courses of
cisplatin and 120 hour 5-FU infusion were given after surgery and
before radiotherapy. Following the demonstration of the feasibility
of this approach two pilot studies were activated by the RTOG in
1981, one using induction chemotherapy followed by surgery and
postoperative radiotherapy in respectable patients, while the
second uses the same chemotherapy after surgery and
before radiotherapy. The side effects of chemotherapy were the
same regardless of the sequence of chemotherapy in relation to the
definitive treatments. Survival favored chemotherapy in the
middle “sandwich”, in spite of more stage IV patients and poorer
performance status in this group. This led to a phase II trail RTOG
83-22, Head and Neck Cancer Inter Group I-0034) in which after
surgical resection patients are stratified and randomized to receive
radiotherapy or three courses of cisplatin and 5-FU infusion
followed by radiotherapy.
60. Combined chemo-radiotherapy
Since the late 1960s several efforts were made to commune
chemotherapy with radiotherapy. The concept of combining
chemotherapy and radiation in the treatment of locally advanced
squamous cell carcinoma of the head and neck, particularly
unresectable or inoperable lesions, is attractive.
Many single agents or combinations of drugs were used with
radiotherapy . The most common single agents selected for
combination with irradiation were, hydroxyurea, methotrexate or
bleomycin. The efficacy of these agents combined with radiotherapy
has not been established in randomized oral cancer, which often results
in interruption of therapy.
The search for better and safer agents to combine with
radiotherapy led to the administration of Cisplatin. Cisplatin is an
active agent in squamous cell cancers of the head and neck. It does not
produce mucositis of the oral cavity and should not interfere with the
delivery of radiotherapy. Cisplatin possesses properties of
radiosensitization that have been observed both in vitro and in vivo. It
has been suggested that the cytotoxic activity of cisplatin is
61. independent of cellage, and that radiation enhancement is both dose
and cell cycle phase dependent.
The combination of cisplatin and radiotherapy produced high
CR rates when given preoperatively in resectable stage III head and
neck malignancy and IV head and neck cancer or as the total
treatment in unresectable and/or inoperable disease. Also, this
combination is being tested as postoperative treatment at Wayne
State University in Detroit.
Because of the high complete response rate obtained with
the combination of cisplatin and 5-FU, this two drug regimen
was added to radiotherapy, and resulted in improved local
control. The combination of the cisplatin and radiotherapy is
being compared to radiation alone in phase III randomize trails
by ECOG, RTOG, and SWOG.
We feel that chemo-radiotherapy may play an important
role in the treatment of patients with locally advanced head and
neck cancer and clinical investigation in this area continues.
62. Chemotherapeutic agents used concurrently with
radiotherapy in advanced cancers
Methotreaxate
Hydroxyurea
5-Fluorouracil
Bleomycin
Cisplatin
Combined Agents
Bleomycin, vincristine, and methotrexate (BVM)
Bleomycin, and methotrexate
Bleomycin, Adriamycin,* and 5-FU
Bleomycin, and cytoxan
Bleomycin, cytoxan, and vincristine
Mitomycin-C, and 5-FU
Cisplatin, and 5-FU
5. Adrimycin (Adria Laboratories, Columbus, OH)
Chemotherapy After Radiotherapy
It has been reported that chemotherapy is most effective in
animal models when used for the eradication of small tumor
masses. Thus, chemotherapy administered after the definitive
63. treatments of surgery and/or radiotherapy may be efficacious in
eradicating minimal residual disease.
Randomized trails of single agent chemotherapy
(methotrexate or cisplatin) post definitive treatments of surgery
and/or radiotherapy were initiated in many cooperative
groups. In the NCI head and neck contract trial one of the
experimental arms required that six doses of cisplatin be
administered following one course of cisplatin plus bleomycin,
surgery and postoperative radiotherapy. Only about 10% of the
patients finished the total six courses while about 30% either
progressed or died, or refused therapy respectively.
Chemotherapy postdefinitive treatment is an important concept
that needs further evaluation.15
64. DRUG SENSITIVITY TO VARIOUS LESIONS,
THERAPY REGIMES
Chemotherapy for recurrent or metastatic SCC H&N
When a patient relapses after extensive surgery or radiation
therapy, treatment options are limited. Traditionally,
chemotherapy has been used in this patient population, with
chemotherapeutic single agents and combination chemotherapy
being evaluated for their response as well as their impact on the
patient’s quality of life. Four drugs have been noted to have
major activity in recurrent and metastatic SCC H&N. They are
(1) methotrexate, (2) cisplatin, (3) belomycin, and (4) 5-
fluorouracil. Other chemotherapeutic agents are noted to have
activity but are not as frequently used.
Methotrexate
Include in the antimetabolite class of agents, methotrexate
exerts its cytotoxic effect through inhibition of the enzyme
65. dihydrofolate reductase. This enzyme is responsible for
maintaining the intercellular pool of folates in reduced state,
which is required for the synthesis of the purine nucleotides.
For most oncologists, this is the standard chemotherapeutic
agents to which other single agents and combinations are
compared. The overall response rate using methotrexate as single
agents approximately 31%, with predominantly partial response
seen and few complete response noted. The initial dose is
40mg/m2
, given intravenously weekly until toxicity is noted,
usually in the form of mucositis or leucopenia. Various doses and
schedules have been used, including leucovorin as a bone marrow
protector in the higher doses. Nevertheless, pooled response rates
are very similar between the moderate and high doses of
methotrexte, and toxicity plus cost are more appreciable at the
higher doses.
Cisplatin
Cisplatin is considered a heavy metal compound and is
believed to exert its activity by causing DNA cross-linking. This
66. agent has been extensively evaluated for patients with recurrent
SCC H&N, with single-agents activity in the range of 28%.
Cisplatin has been evaluated when given on a weekly basis,
every 3 weeks as an intravenous bolus, or by continuous infusion.
All schedules have shown similar response rates. The issue of
dose intensity has also been addressed, with dose-realted toxicity
being a limiting factor, particularly involving renal toxicity and
neurotoxicity. The typical dose used has been between 80 and
100mg/m2
, with no clear advantage see when higher doses are
used. Cisplatin is usually given every 3 to 4 weeks, with pre and
post-hydration plus mannitol infusion to protect renal function.
Bleomycin
Bleomycin is a mixture of glycopeptides considered in the
class of antibiotic considered in the class of antibiotic neoplastic
agents with activity in the G2 and mitotic phases of the cell cycle.
It has been one of the more frequently used agents for head and
neck cancer and has a single agent response rate of approximately
21%. Bleomycin has been administered as a bolus or by
continuous infusion, with equal activity in both continuous
67. infusion, with equal activity in both schedules but with a
suggestion of an improved toxicity profile when the continuous
infusion, with equal activity in both schedules but with a
suggestion of an improved toxicity profile when the continuous
infusion schedule is used.
The dose-limiting toxicity of bleomycin is its cumulative
effect on pulmonary function, making it difficult to administer
after several courses. The single-course dosage frequently used is
10 to 15 mg/m2
daily for 3 to 4 days every 3 to 4 weeks.
5-Fluorouracil
One of the most frequently used chemotherapeutic agents
for head and neck cancer, 5-FU is usually used in combination
with cisplatin. 5-FU is pyrimidine antimetabilite that is converted
intracellularly to fluorodeoxyuridine monophosphate (5-F-
DUMP); a potent inhibitor of thymidylate synthetase, thereby
inhibiting DNA synthesis.
Another way -5-FU mediates its activity is by forming
fluorouridine triphosphate (FUTP), which is incorporated into a
interferes with the function of RNA. Single-agent response rate
68. with 5-FU is approximately 15%. 5-FU has been extensively used
with cisplatin because of preclinical synergy noted.
Recently, it has been observed that 5-FU can be potentiated
when used in conjunction with leucovorin, which is the reduced
form of folate. Leucovorin stabilizes the 5-FU and thymidylate
synthetase tenary complex. When 5-FU is administered as a bolus
daily for 5 days, the dose-limiting side effect is predominalty bone
marrow suppression. If the schedule is altered to a continuous
venous infusion over 24 hours daily for 4 to 5 days, the limiting
toxicity changes to mucositis, diarrhea, and cutaneous erythema.
Cardiac toxicity has also been noted. The continuous infusion
schedule was used in an effort to reduce myelosuppression, but,
indeed, it seems to have improved the activity of this drug in SCC
H&N. The dosage most frequently used has been 800 to 1000
mg/m2
by continuous intravenous infusion for 72 to 96 hours.
Other single agents, not as widely used but with reported
activity in SCC H&N in the range of 15% to 36%, are the
following: (1) carboplatin, an analogue of cisplatin whose dose-
limiting toxicity is myelosuprresion, specifically
69. thrombocytopenia (2) cyclophosphamide and its analogue,
ifosfamide, and hydroxyurea; (3) general classes of drugs with
limited single – agent activity, including the anthracylines
(doxorubicin), the vinca alkaloids, mitomycin, and the nitrosureas.
Combination chemotherapy for recurrent or metastatic SCC
H&N
In the 1970s, the many trails using combination
chemotherapy for patients with recurrent or metastatic SCC H&N
combined the active single agents cisplatin, bleomycin, and
methotrexate. The response rates noted were encouraging, with
the cisplatin-based combination thought to be superior to the non-
cisplatin-based regimens.
In the 1980s, investigators at Wayne State University
combined cisplatin with 5-fluorouracil, both as a bolus and by
continuous intravenous infusion for 96 hours. The initial results
were very encouraging, with an objective response rate of 78%
noted; more importantly, a 29% complete response rate was
obtained for patients with recurrent and metastatic disease. Other
investigators have used the cisplastin/5-FU combination with the
70. same dose and schedule but have obtained overall response rates,
usually in the range of 25% to 30%, with approximately 10%
achieving a complete response.
Efforts have been made over the past several years to
improve the response rates of the cisplatin 5-FU combination.
Some of this research efforts has focused on (1) substituting the
analogue carboplatin for cisplatin, (2) modulating 5-FU with
leucovorin, and (3) dose escalating the cisplatin combined with
the use of chemoprotectors to try to prevent cisplatin-related
toxicities. Unfortuanately, these efforts have failed to
significantly improve the response rate of this combination, and
no overall improvements have been seen with these approaches.
Eleven randomized trails have looked at comparing single
agents, such as cisplain, 5-FU, and methotrexate, versus
combination chemotherapy, including cisplatin and 5-FU, for
patients with recurrent or metastatic SCC H&N. Review of these
studies reveals that, although slightly higher response rates have
been noted using combination chemotherapy, this has not
translated into an improved disease-free or overall survival
71. advantage. In addition, combination chemotherapy has added
toxicity and cost for the patient when compared with single
agents.
Although higher responses and, in particular, complete
responses, can be obtained with the use of cisplatin and 5-
fluororuacil, more toxicity is noted with this combination than
with single agents.
Primary Chemotherapy
Primary chemotherapy refers to the use of chemotherapy,
given either before local therapy, concurrent, with radiation, or
after local treatment has been completed. The rationale for using
chemotherapy prior to local treatment is based on factors such as
(1) an improved patient performance status, (2) an intact vascular
supply to the tumor bed, and (3) the eradication of
micrometastasis to prevent regional and distant metastases.
Induction (Neoadjuvant)
The initial observation made was that response rates using
single agents, such as cisplatin, bleomycin, and methotrexate,
were higher for patients who had not received prior local therapy
72. than for patients in whom disease recurred. In the 1970s,
Randolph et al combined cisplatin and bleomycin for two cycles
prior to local treatment. In this study, the combination of cisplatin
and bleomycin as induction chemotherapy yielded an overall
objective response rate of 71%, with a 20% complete response
rate. Subsequently, investigators at Wayne State University
combined cisplatin and infusional 5-FU for three cycles prior to
local treatment and reported an 88% overall response rate, with
54% of the patients achieving a complete response.
Other investigators have also used the cisplatin and 5-FU
regimen for three courses prior to local therapy with less favorable
results. Parts of the disparity can be explained by patients
selection factors, because patients with N2 or greater disease have
been noted to obtain a complete response rate in the range of 20%.
The pilot feasibility studies pointed to an improved overall and
complete response rate obtained with induction chemotherapy,
without compromising local therapy.
Concurrent Chemoradiation Therapy
73. Although there have been no new agents developed to add
to the response rate of combination chemotherapy for patients
with locally advanced, unresectable SCC H&N, the concurrent use
of single agents, such as bleomycin, 5-FU, methotrexate, hydroxy-
urea, mitomycin-C, and cisplatin, with radiation therapy has been
investigated.
The rationale for combining these two modalities is based
on preclinical data suggesting the radiation-sensitizing effects of
certain chemotherapeutic agents. Also, combining these two
modalities of treatment simultaneously applies the concept of
dose-intensity – administering the largest amount of treatment per
unit time in an effort to over-come any inherent drug or radition
resistance.
Adjuvant Chemotherapy
Chemotherapy given after local therapy has been tried with
the rationale of eradicating micrometastases and thereby possibly
reducing the local, regional and distant metastatic rate.
Unfortunately, of the six randomized trials using chemotherapy in
this fashion, none has shown a survival advantage. Nevertheless,
74. one large study showed a statistically significant decrease in
distant metastases for patients receiving chemotherapy after local
therapy, even though overall survival rates in both arms were not
different.
Nasopharyngeal cancer
Standard treatment for nasopharyngeal carcinoma
worldwide has been radiation therapy because of this tumor’s
known radiation sensitivity and poor anatomic location, making
surgical intervention difficult. In fact, early-stage disease is well
controlled with radiation therapy alone, but in advanced stage
disease, survival is considerably less. For example, for Stage III
disease using radiation therapy alone, 5-year survival has been
reported in the range of 15% to 40% and for Stage IV disease, it is
only 0% to 30%.
Patients with nasopharyngeal carcinoma have a high
likelihood to developing distant metastasis, which seems to
correlate with the amount of cervical adenopathy. In patients with
bilateral neck involvement, there is an established 80% chance for
75. developing distant metastases at a later date, usually involving the
lung, liver, or bone.
Nasopharyngeal carcinoma is believed to be a
chemosensitive tumor; in fact, multiple single agents, such as
cisplatin, 5-FU, methotrexate, bleomycin, the vinca alkaloids, and
doxorubicin, have known activity in this disease. Various studies
have reported rate, of which less than 20% are complete
responders, with the use of cisplatin and non-cisplatin-based
regimes for patients with recurrent or metastatic nasopharyngeal
carcinoma.
Salivary gland carcinoma
Salivary gland carcinomas make up approximately 5% to
10% of all head and neck malignancies. These tumors
demonstrate very diverse anatomic, histologic, and biologic
behaviour. Traditionally, treatment for these tumours has been
surgery with or without radiation therapy. Chemotherapy has
been reserved for patients with recurrent and/or metastatic disease,
and the benefits of chemotherapy have been predominantly
palliative for this group of patients. A number of single agents
76. have shown activity in this disease, but the most active and
frequently used are cisplatin, doxorubicin, 5-FU,
cyclophosphamide, and methotrexate.
Depending upon the histologic type of the tumor,
methotrexate, for example, has been shown to have a single-agent
response rate of approximately 36% in mucoepidermoid cancer,
which is similar to the activity seen for this agent in SCC H&N.
However, for other histologic types of salivary tumours, the
response rate with methotrexate is much lower, approximately
6%. In contrast, doxorubicin is relatively inactive in
mucoepidermoid carcinoma but is active in other salivary gland
histologic types. Single-agent cisplatin has also been extensively
used with a wide range of response rates from 17% to 70%.
Multiple combinations of the most active agents have been tested,
with the most frequent combination being cisplatin and
doxorubicin, with or without 5-FU or cyclophosphamide. The
responses with doxorubicin-based combinations have been in the
range of 35% to 100% with a median response of approximately
50%.
77. Miscellaneous groups
A number of diverse histologic tumors present less
commonly in the head and neck area for which chemotherapy has
been utilized. These include sarcomas, lymphomas,
esthesioneuroblastomas, neuroendocrine carcinomas, and Merkel
cell carcinomas.
Sarcomas
Sarcomas can arise from either the bone or soft tissues in the
head and neck but are rare. When they d occur, the most common
of these tumors are the osteogenic sarcomas, malignant fibrous
hitiocytomas, rhabdomyosarcomas, fibrosarcomas, synovial
sarcomas, and angiosarcomas.
Surgery and radiation therapy remain the treatment of
choice for local disease, but depending upon the extent of disease,
grade and location, local and regional recurrences can be
significant, with distant metastases predominantly involving the
lung, liver and bone.
Chemotherapy, particularly with doxorubicin-based
regimens, has been used and can provide palliation. Response
78. rates with chemotherapy are similar to those seen for other sites
and are largely partial response. For one particular subtype,
rhabdomyosarcoma, chemotherapy added to surgery and radiation
therapy has been reported to improve 5-year survival compared
with that seen with surgery and/radiation therapy alone.
Lymphomas
Both Hodgkin’s and non-Hodgkin’s lymphomas can present
in the head and neck area. When the disease is localized to the
head and neck, the treatment usually consists of radiation therapy
only. However, this disease is frequently found in multiple areas,
and chemotherapy and radiation therapy are used with substantial
success. The most commonly used chemotherapeutic agents for
the lymphomas are the alkylating agents (i.e., cyclophosphamide)
in combination with doxorubicin and vincristine. Prednisone is
also incorporated into these regimens.3
79. MULTIDISCIPLINARY APPROACH TO ADVANCED
SQUAMOUS CARCINOMA OF THE HEAD AND NECK 21
STAGING
MEDICAL ONCOLOGY
RADIOTHERAPY
SURGICAL ONCOLOGY
DENTISTRY
Chemotherapy
No treatment
Adjuvant
chemotherapy
If response to
chemotherapy
Radiotherapy
and/or surgery
If no response to
chemotherapy
80. Price-Hill Schedule A For Head and Neck Cancer 19
Hydrocortisone
500mg IV
Hydrocortisone
500mg IV
5FU 500mg IV
MTX
100mg
IV
MTX
100mg
IV
MTX
100mg
IV
BLEOMYCIN
Vincristine 2mg
IV
15mg 15mg 15mg 15mg
Folinic acid
83. Results of the Combination of Cisplatin I and 5-FU In
Patients With Recurrent Head and Neck Cancer 15
Authors Year Drug Schedule No. of
Patients
Response %
CR Overall
Kish, et al. 1984 C 1000 mg/m2
d1
5-FU 1.0 g/m2
/24 h d1-4
30 27 70
Rowland, et al. 1984 C 1000 mg/m3
d1
5-FU 1.0 g/m2
/24 h d1-4
21 24 71
Creagan, et al. 1984 C 1000 mg/m3
d1
5-FU 1.0 g/m2
/24 h d1-4
20 - 25
Merlao, et al. 1984 5-FU500 mg/m2
/6 h d1-4
Leucovorin 200mg/m2
/dd1-4
C 50 mg/m2
d5
17 0 6
Sridhar, et al. 1984 C 100 mg/m2
d1
5-FU 40 mg/m2
/h d2-6
20 17 72
Kish, et al. 1985 C 100 mg/m2
d1
5-FU 1.0 g/m2
24 h d1-4
18 22 72
Kish, et al. 1985 C 100 mg/m2
d1
5-FU600mg/m2
bolus d1&8
20 10 20
Merlano, et al. 1985 C 20 mg/m2
d1-5
5-FU400-200/m2
bolusd1&5
27 15 59
Dasmahapatra,
et al.
1985 C 100 mg/m2
d1
5-FU 1.0 g/m2
/24 h d1-5
18 - 11
Amrein,
Waitzman
1985 C 80 mg/m2
/24 h d1
5-FU 800 mg/m2
24 h d2-6
39 18 46
Raymond, Cyman 1985 C 100 mg/m2
d1
5-FU 1.0 g/m2
24 h d1-5
16 Not
Stated
75
Fosser, et al. 1985 C 100 mg/m2
d1
5-FU 1.0 g/m2
/24 h d1-5
21 19 62
84. SINGLE AGENT ACTIVITY 22
Drug Dose Schedule Evaluable
Patients
Responsea
Cyclophosphamide 8-10 mg/kg IV 56 2 CE, 35 improved
4 mg/kg/dy IV
4-60 mg/kg single dose
150-300mg/dy; then
100-200 mg/day PO
15 2 improved
2g in divided doses for
8 days; then 100
mg/day PO
6 3 PR, 3 improved
Cyclophosphamide IV, PO, IP, or
intrapleural ranging
from 100mg daily PO
to 8g IV loading dose
preceding PO therapy
4 2 excellent and 2
moderate
responses
Cyclophosphamide 50-200 mg/day PO 1 Improved
30mg/kg IVP; then 10-
15 mg//kg q1-2 wks
Cyclophosphamide Various IV and PO
doses
4 1 improved
Chlorambucil 0.2 mg/kg/day X 42
days PO
34 1 CR, 4 PR
Nitrogen mustard Total dose, 0.5-0.8
mg/kg
2 None
0.6mg/kg in 3 divided
doses
41 5 improved
5-FU 15mg/kg/day X 5 IV;
then 7.1mg/kg every
other day until toxicity.
Maximum loading dose
per day, 1,000 mg
84 1 CR, 4 PR, 20
improved
5-FU 1,000 mg/day X 5; then
500mg every other day
until toxicity
2 2 improved
5-FU 4-8mg/kg/day X 14-42
days
17 3 improved
5-FU 15-20 mg/kg/wk 12 1 CR, 1 PR
85. Drug Dose Schedule Evaluable
Patients
Responsea
Hydroxyurea 80mg/kg q 3 days X 6
wks and 40 mg/kg PO
in 2 divided doses per
day X 21 days;
escalated to 60
mg/kg/day after 21
days if not toxic
1
10
1 improved
3 improved
Vinblastine 0.1 mg/kg/wk to a
maximum of 0.3
mg/kg/wk IV
23 4 PR 7, improved
Procarbazine 150-400mg/day PO or
250-1,250mg single
dose IV
31 3 improved
Adriamycin 60-75 mg/m2
IV q 3
weeks
12 0
Adriamycin Review of various IV
dose schedules, i.e., 60-
90 mg/m2
, q 3 weks;
20-30 mg/m2
/day X 3, q
3 wks; 0.4mg/kg day 1,
2, 7, 8, 9, 10, q 2 wks; 1
mg/kg/day, q 7 days
and 75 mg/m2
: IA over
7 2 h
76 11 PR
Mitomycin C 50mg/kg/day X 6; then
50 mg/kg every other
day until toxicity
4 0
a
CR = Complete response; PR = Partial response (50% or more in tumor
measurements); Improved = Less than a PR not quantitated
86. Selected Multidrug Combination in recurrent and
Metastatic Disease22
Investigator
Treatment
Evaluable
Patients
CR +
PR
Response
Rate (%)
Median
Duration
(months)
Wittes et al. CDDP 2 mg/kg IV q 3 wks 24 3 13 4
Bleo 0.25 mg/kg IV daily until
toxicity, 1-2 mg daily
maintenance
Moran et al.
(1982)
CDDP 50-60 mg/m2
IV q 22
days (day 2)
MTX 30 mg/m2
IV (day 1)
23 8 35 4
Medenica et al. Bleo 15 mg IV wk 26 13 50 8.5
(mean)
Vogl and
Kaplan (1979)
MTX 40 mg/m2
IM day 1 &
15
31 19 61 CR 7+
Bleo 10 mg/m2
IM day1, 8, 15 PR3
CDDP 50 mg/m2
IV day 4; 3-
wk cycles
Caradonna and
Paldine (1979)
Bleo 15 mg/m2
IV day 1 17 14 74 4
MTX 20 mg/m2
IV day 1
CDDP 120 mg/m2
IV day 2
Murphy et al.
(1980)
CDDP 100 mg/m2
IV day 2 24 11 46 5
MTX 30 mg/m2
IV days 1&15
Bleo 30 mg ± day 1 weekly X
6
Von Hoff et al.
(1981)
CDDP 50 mg/m2
5 X day 1 26 9 35 3
Bleo 6 U/m2
SC q 8 h X 12,
days 1-4
MTX 7.5mg/m2
IM days 4-6
Pitman et al.
(1983)
MTX 124-250 mg IV 23 15 65 PR3
5-FU 600 mg/m2
IV 1h later CR6
Leucovorin 10 mg/m2
q 6 h X
6 given weekly
Ringborg et al.
(1983)
Same as above: MTX + 5-FU
+ leucovorin
16 9 52 Not
available
87. Investigator
Treatment
Evaluable
Patients
CR +
PR
Response
Rate (%)
Median
Duration
(months)
Huang et al.
(1980)
Bleo 10 U SCC days 1 and 4 38 Jacobs
(1982)
Same as
above:
MTX + 5-
FU+
leucovorin
30 517
MTX 20 mg PO days 1 and 4
Vinblastine 8 mg/m2
IV day 1
CCNU 175 mg/m2
PO day 1
Hydroxyurea 2 g PO days 1
and 4
Woods et al.
(1979)
Vincristine 2 mg IV day 1 33 8 24 4
MTX 200 mg/m2
24-h IV
infusion with leucovorin
rescue, day 1
Bleo 15 mg/day 48-h IV
infusion day 2
Creagan et al.
(1981)
Adriamycin 40 mg/m2
day 1 25 16 64 7
Cyclophosphamide 400
mg/m2
day 3
CDDP 40 mg/m2
every 21
days cycle
Kish et al.
(1982)
CDDP 100 mg/m2
day 1, q 3
wks
30 21 70 PR6.5
5-FU 1,000 mg/m2
days 1-4
by continuous IV infusion
CR11
88. ROUTE OF ADMINISTRATION OF VARIOUS
CHEMOTHERAPEUTIC AGENTS
The administration of chemotherapy has not always been as
it is today. As recently as the 1950s, the physician administered
the medications and the nurse was left to care for any side effects
(Lind and Bush 1987). The first chemotherapy drug. A nitrogen
mustard (mechlorethamine), was discovered in the 1940’s and in
comparison to other areas of medicine, the field of oncology was
still in its infancy. As the number of available drugs increased and
the technology of chemotherapy administration became more
complex.
ROUTES OF ADMINISTRATION
The goal of chemotherapy administration is to optimize drug
availability. In an attempt to deliver drugs in high concentrations
to areas of greatest clinical need and to improve the antitumor
effects, many diverse routes of drug administration have been
developed (Haskel 1980). The current routes of administration
include:
intrathecal (IT)
89. intra-arterial (IA)
intracavitary (IC)
subcutaneous (SQ)
intramuscular (IM)
topical (TOP)
oral (PO)
intravenous (IV)
The following three routes of administration allow for high
drug concentrations in the disease area while minimizing the
systemic concentrations, and thus the side effects:
intrathecal
intra-arterial
intracavitary
Administering chemotherapy intrathecally allows the drugs
to reach the central nervous system to prevent or treat local
disease. The majority of chemotherapy agents do not cross the
blood-brain barrier, so they must be delivered directly into the
cerebrospinal fluid. This is accomplished by either:1) a lumbar
puncture or 2)utilizing an indwelling subcutaneous cerebrospinal
90. fluid reservoir, such as the Ommaya reservoir (Heyer-Schulte del
Caribe, Anasco PR). The benefits and risks to the patient must be
determined before either method of administration is chosen. To
put it concisely, include: 1) having a lumbar puncture performed
for each treatment (weighing the pain and potential complications
that procedure involves) or 2) the potential complications of
surgically inserting and Ommaya reservoir, but utilizing a
consistent port for each treatment. The Ommaya reservoir is a
mushroom-shaped, reusable, self-sealing, silicone port which is
connected to a catheter placed in the ventricle (Figure ). The
reservoir is accessed by inserting a hypodermic needle, usually a
small-gauged butterfly needle with an attached three-way
stopcock and syringe, directly into the dome. During the
procedure an amount of cerebrospinal fluid, equal to the amount
of medication to be injected, is removed. The medication is
injected into the reservoir and, once the needle is removed, the
domed reservoir is manually compressed and released to mix the
medication with the cerebrospinal fluid (Brown 1987). This
91. procedure is usually performed by a physician using strict aseptic
technique.
Cerebrospinal fluid reservoir and mode of use
Intra-arterial infusions treat an isolated organ or inoperable
tumor. The chemotherapy agents are administered through a
catheter inserted into an artery usually in the liver, head, neck, or
brain. The celiac artery is used to treat the liver, the external
carotid artery for the head and neck area, and the internal carotid
artery for brain tumors (Johnston and Pratt 1981). The catheters
are inserted into the artery surgically with general anesthesia or
using angiographic catheterization and a local anesthetic. The
92. catheters are then connected to either an implanted or portable
pump. There are two impantable pumps currently being used: the
Infusaid pump (Shiley Infisaid Inc, Norwood, MA), and the
Medtronic pump (Medtronic, Minneapolis). The Autosyringe
Division, Hooksett, NH), is an example of a portable systems used
for intra-arterial infusions.
Portable infusion pump
Three other modes of drug administration are used less
frequently:
subcutaneous
93. intramuscular
topical
Many of the antineoplastic agents are irritating or damaging
to body tissue, so it is inadvisable to give a subcutaneous or
intramuscular injection of these agents. Some drugs that can be
given by the subcutaneous route are cytosine arabinoside
(ARA-C) and the interferons, while bleomycin and methotrexate
can be given intramuscularly. L-asparaginase is one drug that may
be given either by the subcutaneous or intramuscular route.
Topical administration has limited usefulness with only
mechlorethamine and 5-fluorouracil cream having this method as
one of their routes of administration, (Dorr and Fritz 1980).
Occasionally, a specific protocol or drug may be administered
using one of the methods.
The last two routes of chemotherapy administration are the
most common:
Oral
Intravenous
94. The oral route is usually preferred but absorption can be
unpredictable. Several factors must be considered before choosing
the oral route: patency and functioning of the GI tract, presence of
nausea, vomiting, or dysphagia, the patient’s state of
consciousness, the patient’s willingness to comply to the schedule,
and the availability of the medication in oral form.
The intravenous (IV) route of administration is the most
common method used to deliver chemotherapy. It allows
absorption of the drug thus providing predictable blood levels
(Brown 1987). Intravenous drugs may be administered through a
peripheral access, a vein in the patient’s arm or hand, or through a
central venous access device, such as a silicone, silastic catherter,
or an implanted infusion port. The three major adviser reactions to
the intravenous route of administration are: phlebitis, venous flare,
and extravasation (Troutman 1985).
There are four methods of intravenous administrations:
push (IVP)
piggyback (IVB)
sidearm
95. infusion, continuous or intermittent
Intravenous push refers to directly administering the
medication into the intravenous cannula, through either an
angiocath or a butterfly needle. A piggyback method denotes there
is a main line of intravenous fluid connected into the intravenous
cannula. The solution to be piggybacked is connected, usually in
the port closest to the patient, into the main intravenous line. The
sidearm method of administration is the route of choice for
chemotherapy with vesicant properties. Again, a main line of
intravenous fluid, freely flowing, is connected into the intravenous
cannula. The physician directly administers the medication,
slowly, into the part closest to the patient while continually
assessing the peripheral IV site for complications and
extravasation. This method, as could the piggyback method,
allows for further dilution of the chemotherapeutic agent with the
main fluid. The two solutions must be compatible. The infusion
method may last from several minutes (bolus infusions) to several
days, 24 hours a day (continuous infusions).
96. Selecting a Vein Assess veins in both arms and hands. Do not
use veins in compromised limbs/lower extremities
Criteria for Vein Selection Appropriate
Choice of
Venipuncture Site
Ideal Vein/Best Location forearm
Large, soft resilient veins in
forearm, hand
Ideal Vein/Undesirable Location
Large, soft, resilient veins in
hand/antecubital fossa; small, thin
veins in forearm
hand
Satisfactory Vein/Best Location
Small, thin veins in forearm/hand forearm
Satisfactory Vein/Undesirable
Location
hand
small thins veins in hand; veins in
forearm not palpable or visible
Unsatisfactory Vein/Undesirable
Location
Consider central
venous line*
small, fragile veins, which easily
rupture, in hand/forearm
Unsatisfactory Vein/Undesirable
Location
Consider central
venous line*
veins in forearm/hand not palpable
or visible
*In some situations, central venous lines are inserted before the patient is
started on a chemotherapy protocol.
97. Dealing with the “veinless” patient
One of the most common dilemmas facing oncology nurses
is trying to administer chemotherapy to the “veinless” patient
(described by Lokich 1978). With the variety of central venous
access devices, both catheters and subcutaneous ports, this issue
doesn’t have to be a problem.
1. In an attempt to dilate the veins, apply moist heat to the
arms for 5-10 minutes (Johnston Early, Cohen and White
1981).
2. Once the soaks are removed, work efficiently while the
veins are dilated.
3. Local vein manipulation may also aid dilation:
a. Appropriate use of a tourniquet or blood pressure
cuff to encourage pooling of venous blood.
b. “Milking” the veins from proximal to distal (elbow
to hand)
c. Gently striking the surface of the vein
98. 4. Catheter selection is very important in this setting. The
veins may well be small and an appropriately sized
needle will decrease trauma.
5. Perform the actual techniques and preparation for
venipuncture according to the institution’s policies and
procedures.
Controversial Issues in Chemotherapy Administration
Issue Solution Rationale
Administration
site
Use antecubital
fossa
Larger veins permit more rapid
infusion and administration of
drugs
Larger veins permit more rapid
circulation of potentially
irritating drugs
Avoid antecubital
fossa
Mobility of arm restricted
Risk of extravasation increased
due to patient mobility
Ealry infiltration and
extravasation difficult to assess
due to subcutaneous tissue
Repair of infiltration would be
difficult and debilitating for the
patient
Needle size Larger gauge (#19-
21 scalp vein
needles)
Potentially irritating drugs
reach circulation sooner, with
less irritation to peripheral
veins
Small gauge (#23-
25)
Smaller gauge needles less
likely to puncture wall of vein;
less scar tissue at insertion site;
and less pain on insertion
99. Increased blood flow around
needle increases dilution of the
drug
Reduced incidence of
mechanical phlebitis
Slower infusion rate – may
reduce side effects, i.e., nausea
and vomiting
Sequencing of
medications
Administer vesicant
first
Vascular integrity decreases
over time, i.e., more stable and
less irritated at the beginning of
treatment
Initial assessment of vein
patency is most accurate
Irritating agents may cause
venous spasm and pain
Administer vesicant
last
Vesicants are irritating, may
increase vein fragility, and
cause spasm at onset of drug
administration. The nurse must
assess whether the spasm and
complaint of pain is an
infiltrate or not
Particular
intravenous
method of
administration
Use sidearm
method
Freely running intravenous
lines allow for dilution of drugs
Use direct IV push
method
Integrity of the vein can be
more easily assessed
Extravasation can be noted
earlier
100. DRUG DELIVERY SYSTEMS
One of the fastest growing areas in the oncology setting
today is the area of drug delivery systems – catheters, implantable
ports, and infusion pumps. By the time this book is published,
numerous new products will be available that were only a thought
at the time the authors were formulating this section.
Previously, a venous access device was only indicated when
the patient had unsatisfactory veins for further cancer therapy.
Now there are several indications for early placement of a venous
access device (Simon 1987). Patients receiving continuous
infusions of chemotherapy, nutritional supplements, or antibiotics
either at home or in the hospital are also ideal candidates for such
devices.
Two central venous access devices will be discussed in this
section: silastic right atrial catheters and implantable venous
access ports (VAP).
101. Silastic Catheters
The Broviac silastic catheter (Davol Inc., Cranston, R.I.)
was first reported in 1973. It was a small-bore, 18-gauge catheter
that as originally described as being safe for infusing Total
Parenteral Nutrition (TPN) on a long-term basis (Simon 1987). In
1979, the larger bored, 16-gauge Hickman catheter (Davol Inc.,
Cranston, R.I.) was reported to be sage for intravenous infusions
including blood transfusions and blood samples (Simon 1987).
The Hickman-Broviac catheters became the front runners for not
only a type of central venous access device but also for a surgical
technique of inserting such catheters. The Hickman-broviac
technique for catheter insertion was designed to reduce an
undesirable complication in the long-term use of these catheters:
infection (Raaf 1985).
Implantable Venous Access Ports (VAPs)
Venous access ports (Vaps) consist of two main features:
the port housing made of either plastic, stainless steel, or titanium
with the resealable silicone septum, and the silastic catheter which
102. is either preattached to the housing or comes as a separate piece
needing attachment during the insertion procedure.
A “tunnel” is made under the skin toward the collarbone for the
catheter. The catheter is inserted into the subclavian or internal
jugular vein (Lawson and Finley 1988). Both the port and the
catheter are sutured into place, including closing the pocket
containing the port. Once this is completed, the VAP is completed
under the skin.12
103. MARKERS USED TO INTERFERE WITH CELL
GROWTH TO STUDY THE PERFORMANCE OF
THE DRUG
Biologic markers of prognosis
Although certain clinical parameters such as disease stage,
tumor histology and grade, site of origin, nodal metastasis, and
perineural spread generally correlate with the prognosis of patient
with cancer of the salivary glands, there is still a great deal of
heterogeneity in outcome among patient with similar clinical
parameters. The inability of clinical parameters to consistently
predict the outcome of patients with cancer of the salivary glands
has led to the recent extensive study of various biologic markers
as predictors of prognosis in patients with cancer of the salivary
glands.
Tumor suppressor Genes and Oncogenes
Cancer is disease of altered cellular genes. These altered
genes, in turn, initiate or promote the malignant phenotype by
inducing changes in key events involved in regulation of the cell
104. cycle. Examples of such altered gene expression include
inactivation of tumor suppressor genes and or overexpression of
oncogenes. Several such alterations have been investigates as
potential prognostic indicators in patients with salivary gland
cancers.
Point mutation of TP53 (formally known as p53), a tumor
suppressor gene, was associated with an increased likelihood to
tumor recurrence in patients with ACC. More recent studies
emphasize the prognostic value of TP53 alteration as an
independent prognostic marker and its association with
radiotherapy and chemotherapy resistance in patients with ACC.
TP53 expression was detected in more than one third of patients
with high-grade cancer of the salivary glands, and it has been
implicated in carcinogenesis of tumors of salivary glands origin.
Loss of wild-type TP53 and activation of C-MYC and RAS p21
proto-oncogenes may play important roles in the malignant
transformation of salivary gland pleomorphic adenoma.
Another example of a tumour suppressor gene is p27 (Kipl),
a cyclin-dependent kinase inhibitor negatively that regulates the
105. G1 phase progression of the cell cycle by binding to the cyclin
E/cyclin-dependent kinase 2 complex. A recent study of the
expression of p27 in patients with MEC indicated its usefulness as
a marker of tumour progression aggressiveness and prognosis.
Significant correlation was found between low p 27 expression
and tumour with high-grade, advanced T-stages, positive nodal
status, and advanced clinical stages (p=0.01). Multivariate
analysis indicated that p27 expression was a significant predictor
of overall survival among these variables poor prognosis.
DNA Ploidy
Several studies have suggested a potentially important prognostic
role for flow cytometric measurement of DNA content in salivary
neoplasms. Significant statistical correlation between DNA
content and tumour size, histologic grade, lymph node metastasis
and survival was found in patients with malignant tumors of the
salivary glands. High grade tumours such as undifferentiated
carcinoma, adenocarcinoma, salivary duct carcinoma, squamous
cell carcinoma, and pleomorphic adenoma were more likely to
have aneuploid DNA stem lies, and the survival time of patients
106. with aneuploid tumours was considerably lower than for patients
with diploid tumours. Aneuploid tumors are also more likely to be
present with TP53 abnormalities. These data emphasize the
potential usefulness of DNA measurements as a prognostic
indicator in patients with malignant tumours of the salivary
glands.
Markers of Cellular Proliferation
Several markers of cellular proliferation were recently reported to
bear prognostic significance in patients with cancer of the salivary
glands. The Ki-67 index, a marker of cellular proliferation, was
found to be significantly higher in malignant than benign
neoplasms of the salivary glands. The Ki-67 index also correlated
significantly with malignant tumour grade and patient survival.
Among patients with ACC, expression of Ki-67 was related to the
morphologic type – the solid subtype had the highest frequency of
Ki-67-positive cells. Because this subtype is recognized as the
most aggressive of these tumours. Ki-67 may have the potential
for providing an indication of the clinical behavior of ACC.
107. Argyrophilic Necleolar Organizer Regions
Several studies have found a positive correlation between
the argyrophilic nucleolar organizer region (AgNOR) count and
the aggressive clinical course of malignant salivary gland tumors.
Vuhahula and colleagues measured Ag NOR counts in 34 patients
with ACC to determine (1) whether AgNOR count correlates with
histologic grade and (2) whether AgNOR count can offer any
additional prognostic advantage over histologic grading.
All unfavourable cases had high AgNOR counts regardless
of histologic grade, suggesting that the metabolic alterations
associated with the degree of malignancy of ACC may be partly
portrayed by the AgNOR count, irrespective of histologic
appearance.
Hormone Receptors
A variety of hormone receptors, including estrogen,
progesterone, and androgen receptors, have been identified in and
correlated with the clinical behavior of salivary gland tumors.
Shick and coworkers confirmed the presence of progesterone