Cancer chemotherapy and treatment involves several methods. Chemotherapy uses drugs to prevent or treat cancer by killing cancer cells. Common chemotherapies include fluorouracil, capecitabine, and cytarabine which are pyrimidine analogues that interfere with DNA synthesis in cancer cells. These drugs have similar mechanisms of action but different routes of administration and toxicity profiles. Combination chemotherapy uses multiple agents to increase effectiveness while reducing resistance. Careful dosing and administration is needed due to the narrow therapeutic index of chemotherapy drugs.
CANCER: A REVIEW: WORLD'S SECOND MOST FEARED DIAGNOSISCharu Pundir
It is a basic review presentation on cancer, world's second most dreadful disease followed by cardiovascular events, involving basic defination, pathophysiology, screening methods, types of tumor, tumor origin, cancer cell lines, treatment, recent advancements made in the field and diagnosis.
Cancer is the uncontrolled growth of abnormal cells anywhere in a body.
There are over 200 types of cancer.
Anything that may cause a normal body cell to develop abnormally potentially can cause cancer; general categories of cancer-related or causative agents are as follows: chemical or toxic compound exposures, ionizing radiation, some pathogens, and human genetics.
Cancer symptoms and signs depend on the specific type and grade of cancer; although general signs and symptoms are not very specific the following can be found in patients with different cancers: fatigue, weight loss, pain, skin changes, change in bowel or bladder function, unusual bleeding, persistent cough or voice change, fever, lumps, or tissue masses.
Although there are many tests to screen and presumptively diagnose cancer, the definite diagnosis is made by examination of a biopsy sample of suspected cancer tissue.Cancer staging is often determined by biopsy results and helps determine the cancer type and the extent of cancer spread; staging also helps caregivers determine treatment protocols. In general, in most staging methods, the higher the number assigned (usually between 0 to 4), the more aggressive the cancer type or more widespread is the cancer in the body. Staging methods differ from cancer to cancer and need to be individually discussed with your health care provider.
Treatment protocols vary according to the type and stage of the cancer. Most treatment protocols are designed to fit the individual patient's disease. However, most treatments include at least one of the following and may include all: surgery, chemotherapy, and radiation therapy.
There are many listed home remedies and alternative treatments for cancers but patients are strongly recommended to discuss these before use with their cancer doctors.
CANCER: A REVIEW: WORLD'S SECOND MOST FEARED DIAGNOSISCharu Pundir
It is a basic review presentation on cancer, world's second most dreadful disease followed by cardiovascular events, involving basic defination, pathophysiology, screening methods, types of tumor, tumor origin, cancer cell lines, treatment, recent advancements made in the field and diagnosis.
Cancer is the uncontrolled growth of abnormal cells anywhere in a body.
There are over 200 types of cancer.
Anything that may cause a normal body cell to develop abnormally potentially can cause cancer; general categories of cancer-related or causative agents are as follows: chemical or toxic compound exposures, ionizing radiation, some pathogens, and human genetics.
Cancer symptoms and signs depend on the specific type and grade of cancer; although general signs and symptoms are not very specific the following can be found in patients with different cancers: fatigue, weight loss, pain, skin changes, change in bowel or bladder function, unusual bleeding, persistent cough or voice change, fever, lumps, or tissue masses.
Although there are many tests to screen and presumptively diagnose cancer, the definite diagnosis is made by examination of a biopsy sample of suspected cancer tissue.Cancer staging is often determined by biopsy results and helps determine the cancer type and the extent of cancer spread; staging also helps caregivers determine treatment protocols. In general, in most staging methods, the higher the number assigned (usually between 0 to 4), the more aggressive the cancer type or more widespread is the cancer in the body. Staging methods differ from cancer to cancer and need to be individually discussed with your health care provider.
Treatment protocols vary according to the type and stage of the cancer. Most treatment protocols are designed to fit the individual patient's disease. However, most treatments include at least one of the following and may include all: surgery, chemotherapy, and radiation therapy.
There are many listed home remedies and alternative treatments for cancers but patients are strongly recommended to discuss these before use with their cancer doctors.
Cancer causes cell to divide uncontrollably. Cancer is the second-leading cause of death in the world. But survival rates are improving for many types of cancer, thanks to improvements in cancer screening, treatment and prevention. Cancer is caused by changes (mutations) to the DNA within cells.
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread to other parts of the body.
## To understand how cancer develops and progresses, researchers first need to investigate the biological differences between normal cells and cancer cells. This work focuses on the mechanisms that underlie fundamental processes such as cell growth, the transformation of normal cells to cancer cells, and the spread, or metastasis, of cancer cells.
A tumor marker is a substance found in your blood, urine, or body tissue. The term "tumor markers" may refer to proteins that are made by both healthy
....
Cancer causes cell to divide uncontrollably. Cancer is the second-leading cause of death in the world. But survival rates are improving for many types of cancer, thanks to improvements in cancer screening, treatment and prevention. Cancer is caused by changes (mutations) to the DNA within cells.
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread to other parts of the body.
## To understand how cancer develops and progresses, researchers first need to investigate the biological differences between normal cells and cancer cells. This work focuses on the mechanisms that underlie fundamental processes such as cell growth, the transformation of normal cells to cancer cells, and the spread, or metastasis, of cancer cells.
A tumor marker is a substance found in your blood, urine, or body tissue. The term "tumor markers" may refer to proteins that are made by both healthy
....
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
HOT NEW PRODUCT! BIG SALES FAST SHIPPING NOW FROM CHINA!! EU KU DB BK substit...GL Anaacs
Contact us if you are interested:
Email / Skype : kefaya1771@gmail.com
Threema: PXHY5PDH
New BATCH Ku !!! MUCH IN DEMAND FAST SALE EVERY BATCH HAPPY GOOD EFFECT BIG BATCH !
Contact me on Threema or skype to start big business!!
Hot-sale products:
NEW HOT EUTYLONE WHITE CRYSTAL!!
5cl-adba precursor (semi finished )
5cl-adba raw materials
ADBB precursor (semi finished )
ADBB raw materials
APVP powder
5fadb/4f-adb
Jwh018 / Jwh210
Eutylone crystal
Protonitazene (hydrochloride) CAS: 119276-01-6
Flubrotizolam CAS: 57801-95-3
Metonitazene CAS: 14680-51-4
Payment terms: Western Union,MoneyGram,Bitcoin or USDT.
Deliver Time: Usually 7-15days
Shipping method: FedEx, TNT, DHL,UPS etc.Our deliveries are 100% safe, fast, reliable and discreet.
Samples will be sent for your evaluation!If you are interested in, please contact me, let's talk details.
We specializes in exporting high quality Research chemical, medical intermediate, Pharmaceutical chemicals and so on. Products are exported to USA, Canada, France, Korea, Japan,Russia, Southeast Asia and other countries.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
2. Introduction
• The term cancer actually refers to more than 100 different
diseases.
• What is common to all cancers is that the cancerous cell is
uncontrollably growing and has the potential for invading
local tissue and spreading to other parts of the body, a
process called metastases
3. Cancer Prevention
• Because most cancers are not curable in advanced
stages, cancer prevention is an important and active area
of research.
• Both lifestyle modifications and chemoprevention agents
may significantly reduce the risk of developing cancer.
• FDA has approved three vaccines that can help prevent
cancer:
– There are two approved vaccines that prevent infection with
human papillomavirus, which can cause cancers of the cervix,
vulva, vagina, and anus.
– Another approved vaccine prevents infection with hepatitis B
virus, which can cause liver cancer.
4. Cont…
• There are other medications that can be taken orally and
have been used for cancer prevention e.g.
– The selective estrogen receptor modulator (SERM) tamoxifen,
which reduces the risk of breast cancer in premenopausal women.
– Another SERM, raloxifene and the aromatase inhibitor
exemestane both have shown a reduction in breast cancer in
high-risk postmenopausal women
• Smoking cessation is associated with a gradual decrease
in the risk of cancer, but more than 5 years is needed
before a major decline in risk is detected
5. Carcinogenesis
• The exact cause of cancer remains unknown and is
probably very diverse given the vast array of diseases
called cancer.
• It is thought that cancer develops from a single cell in
which the normal mechanisms for control of growth and
proliferation are altered.
• Current evidence indicates that there are four stages in the
cancer development process.
1. Initiation; occurs when a carcinogenic substance encounters a normal cell to
produce genetic damage and results in a mutated cell.
2. Promotion; the environment is altered by carcinogens or other factors to favor
the growth of the mutated cell over the normal cell
3. Transformation (or conversion); occurs when the mutated cell becomes
malignant.
4. Progression; occurs when cell proliferation takes over and the tumor spreads or
develops metastases.
6. Cont…
• There are substances known to have carcinogenic risks,
including chemicals, environmental factors, and viruses.
• Chemicals in the environment, such as aniline & benzene,
are associated with the development of bladder cancer
and leukemia, respectively.
• Environmental factors, such as excessive sun exposure,
can result in skin cancer, and smoking is widely known as
a cause of lung cancer.
• Viruses, including human papillomavirus (HPV), Epstein-
Barr virus, & hepatitis B virus, have been linked to cervical
cancers, lymphomas, and liver cancers, respectively.
7. Cont…
• Anticancer agents such as the alkylating agents (eg,
melphalan), anthracyclines (eg, doxorubicin), and
epipodophyllotoxins (eg, etoposide) can cause secondary
malignancies (eg, leukemias) years after therapy has been
completed.
• Additionally, factors such as the patient’s age, gender,
family history, diet, and chronic irritation or inflammation
may be considered to be promoters of carcinogenesis.
8. Cancer Genetics
• There are 2 major classes of genes involved in
carcinogenesis, oncogenes and tumor suppressor genes.
• Proto-oncogenes are normal genes that, through some
genetic alteration caused by carcinogens, change into
oncogenes.
• Tumor suppressor genes inhibit inappropriate cellular
growth and proliferation by gene loss or mutation.
• The p53 gene is one of the most common tumor
suppressor genes. If p53 is inactivated, then the cell
allows the mutations to occur.
• DNA repair genes fix errors in DNA that occur because of
environmental factors or errors in replication and can be
classified as tumor suppressor genes.
9.
10. Metastases
• A metastasis is a growth of the same cancer cell found at
some distance from the primary tumor site.
• The metastasis may be large, or it may be just a few cells
that may be detected through PCR
• The presence of metastasis at staging usually is
associated with a poorer prognosis than the patient with
no known metastatic disease.
• Cancers spread usually by two pathways: hematogenous
(through the bloodstream) or through the lymphatics
(drainage through adjacent lymph nodes).
• The usual metastatic sites for solid tumors are the brain,
bone, lung, & liver.
11. Tumor Origin
• Tumors may arise from the four basic tissue types:
epithelial, connective (i.e. muscle, bone, and cartilage),
lymphoid, or nerve tissue.
• The suffix -oma is added to the name of the cell type if the
tumor cells are benign.
• A lipoma is a benign growth that resembles fat tissue.
• Precancerous cells have cellular changes that are
abnormal but not yet malignant and may be described as
hyperplastic or dysplastic.
• Hyperplasia occurs when a stimulus is introduced and
reverses when the stimulus is removed.
• Dysplasia is an abnormal change in the size, shape, or
organization of cells or tissues.
12. Cont….
• Malignant cells are divided into categories based on the
cells of origin:
1. Carcinomas arise from epithelial cells
2. Sarcomas arise from muscle or connective tissue.
3. Adenocarcinomas arise from glandular tissue.
4. Carcinoma in situ refers to cells limited to epithelial origin that
have not yet invaded the basement membrane.
5. Malignancies of the bone marrow or lymphoid tissue, such as
leukemias or lymphomas, are named differently.
13. Tumor Characteristics
• Tumors are either benign or malignant.
• Benign tumors often are encapsulated, localized, and
indolent; they seldom metastasize; and they rarely recur
once removed; histologically, the cells resemble the cells
from which they developed.
• Malignant tumors are invasive and spread to other
locations even if the primary tumor is removed; the cells
no longer perform their usual functions, and their cellular
architecture changes; this loss of structure and function is
called anaplasia.
• Usually, once distant metastases have occurred, the
cancer is considered incurable.
14. Diagnosis of Cancer
• Cancer can present as a number of different signs and
symptoms.
• Appropriate laboratory tests, radiologic scans, and tissue
samples are necessary.
• The sample of tissue may be obtained by a biopsy, fine-
needle aspiration, or exfoliative cytology.
• No treatment of cancer should be initiated without a
pathologic diagnosis of cancer.
• During the pathologic workup, genetic analysis may be
done.
15. Cont…
• Depending on the type of cancer, the genetic analysis can
provide the additional information on prognosis of the
malignancy and whether certain therapies may be
appropriate.
• Once the pathology of cancer is established, then staging
of the disease is done before treatment is initiated.
• Cancer staging is usually done according to the primary
tumor size, extent of lymph node involvement, and the
presence or absence of metastases, also referred to as
the tumor, nodes, metastases (TNM) system.
• The stage of the disease is a compilation of the primary
tumor size, the nodal involvement, & metastases and is
usually referred to as stages I, II, III, or IV.
16. Cont…
• Some cancers produce substances (eg, proteins) that are
detected by a blood test
• These may be useful in following response to therapy or
detecting a recurrence; these are referred to as tumor
markers e.g. the prostate-specific antigen (PSA).
17.
18. Treatment
• Surgery may be able to remove all macroscopic disease;
however, microscopic cells may still be present near the
surgical site or may have traveled to other parts of the
body.
• Thus, for chemotherapy-sensitive diseases, systemic
therapies may be administered after surgery to destroy
these microscopic malignant cells; this is called adjuvant
chemotherapy.
• The goals of adjuvant chemotherapy are to decrease the
recurrence of the cancer and to prolong survival.
• Chemotherapy may also be given before surgical
resection of the tumor; this is referred to as neoadjuvant
chemotherapy.
19. Cont…
• Chemotherapy given before surgery should decrease the
tumor burden to be removed (which may result in a shorter
surgical procedure or less physical disfigurement to the
patient) & make the surgery easier to perform because the
tumor has shrunk away from vital organs or vessels.
• Neoadjuvant chemotherapy also gives the clinician an idea
of the responsiveness of the tumor to that particular
chemotherapy.
• Chemotherapy may be given to cure cancers that are
curable, or it may be given to help control the symptoms of
an incurable cancer, which is referred to as palliative
therapy.
20. Response
• The responses to chemotherapy may be referred to as
complete response (CR), partial response (PR), stable
disease (SD), or disease progression.
21. Non-pharmacologic Therapy
• The four primary treatment modalities of cancer are
surgery, radiation, biotherapy, and pharmacologic therapy.
• Surgery is useful to gain tissue for diagnosis of cancer and
for treatment, esp those cancers with limited disease.
• Radiation plays a key role not only in the treatment &
possible cure of cancer but also in palliative therapy.
• Together, surgery and radiation therapy may provide local
control of symptoms of the disease.
• However, when cancer is widespread, surgery may play
little or no role, but radiation therapy localized to specific
areas may palliate symptoms.
22. Pharmacologic Therapy
• Chemotherapy of cancer started in the early 1940s when
nitrogen mustard was first administered to patients with
lymphoma.
• Since then, numerous agents have been developed for the
treatment of different cancers.
23. Dosing of Chemotherapy
• Chemotherapeutic agents typically have a very narrow
therapeutic index.
• The doses of chemotherapy must be given at a frequency
that allows the patient to recover from the toxicity of the
chemotherapy
• Each period of chemotherapy dosing is referred to as a
cycle.
• Each cycle of chemotherapy may have the same dosages;
the dosages may be modified based on toxicity; or a
chemotherapy regimen may alternate from one set of
drugs given during the 1st, 3rd, and 5th cycles to another set
of different drugs given during the 2nd , 4th , and 6th cycles.
24. Cont…
• The dose density of chemotherapy refers to shortening of
the period between cycles of chemotherapy.
• This can accomplish 2 things: 1st, the tumor has less time
between cycles of chemotherapy to grow, & 2nd, patients
receive the total number of required cycles in a shorter
time period.
• Administration of dose-dense chemotherapy regimens
often requires the use of colony-stimulating factors (eg,
filgrastim or granulocyte colony-stimulating factor [G-CSF])
to be administered; These agents shorten the duration and
severity of neutropenia.
25. Cont…
• The chemotherapy regimens that are dose dense tend to
be adjuvant regimens, and the goal of therapy is cure.
• When a chemotherapy regimen is used as palliative
therapy (to control symptoms), the dosages of
chemotherapy may be decreased based on toxicity or the
interval between cycles may be lengthened to maintain
quality of life.
• Another consideration of chemotherapy administration is
the patient.
• Factors that affect chemotherapy selection and dosing are
age, concurrent disease states, & performance status.
• Performance status can be assessed through either the
ECOG Scale or the Karnofsky Scale.
26. Combination Chemotherapy
• The underlying principles of using combination therapy are
to use:
1. Agents with different pharmacologic actions
2. Agents with different organ toxicities
3. Agents that are active against the tumor and ideally synergistic
when used together
4. Agents that do not result in significant drug interactions (although
these can be studied carefully and the interactions addressed)
• When two or more agents are used together, the risk of
development of resistance may be lessened, but toxicity
may be increased.
29. Fluorouracil
• 5-Fluorouracil (5-FU) is a fluorinated analogue of the
pyrimidine uracil.
• Once administered, this prodrug is metabolized by
dihydropyrimidine dehydrogenase.
• 5-FU ultimately is metabolized to fluorodeoxyuridine
monophosphate (FdUMP), which interferes with the
function of thymidylate synthase (TS), which is required for
synthesis of thymidine.
• The triphosphate metabolite of 5-FU is incorporated into
RNA to produce the second cytotoxic effect of 5-FU.
• Inhibition of thymidylate synthesis occurs with the
continuous infusion regimens, whereas the triphosphate
form is associated with bolus administration.
30. Fluorouracil
• Patients with a low activity of dihydropyrimidine
dehydrogenase appear to be at risk for life-threatening
toxicities.
• Folates increase the stability of FdUMP–TS inhibition,
which enhances the activity of the drug in certain cancers.
• 5-FU is metabolized extensively by the liver, but up to 15%
of a dose may be found unchanged in the urine.
• 5-FU has shown clinical activity in several solid tumors,
and is frequently used to treat both breast and colon
cancer.
31. Fluorouracil
• Adverse effects may include stomatitis, diarrhea,
esophagitis, gastric ulcerations, cardiac abnormalities, and
rarely reported cerebellar toxicities.
• Some alopecia may occur, but hair regrowth may occur
with subsequent doses.
• Cryotherapy (using ice chips in the mouth) for 30 minutes
while receiving bolus 5-FU may decrease the severity of
mucositis.
• Neurotoxicity may consist of headaches, visual
disturbances, and cerebellar ataxia.
• Cardiac toxicity may consist of ST-segment elevation,
which appears to be more common in patients with a
history of coronary artery disease.
32. Capecitabine
• Capecitabine is an orally active prodrug of 5-FU and has
shown to be active in tumors of the colon, rectum, and
breast.
• It not only shares the same mechanism but the toxicity
profile is also similar to that of 5-FU.
• There appears to be a higher level of thymidine
phosphorylase intracellularly, which is the enzyme
responsible for converting capecitabine into 5-FU.
• This is believed to make the agent more selective against
malignant cells.
• 30 minutes of a meal to increase absorption of the drug.
33. Capecitabine
• Toxicities include diarrhea, mucositis, palmar-plantar
erythrodysesthesia, nausea, and myelosuppression.
• Palmar-plantar erythrodysesthesia, also called hand–foot
syndrome, refers to redness, itching, and blistering of the
palms of the hands and soles of the feet.
• Significant increases in INR and prothrombin time may
occur within several days when capecitabine is initiated in
patients concomitantly receiving warfarin.
• Phenytoin levels may become elevated related to possible
CYP2C9 inhibition by capecitabine.
• Patients should be instructed to take capecitabine within
30 minutes of a meal to increase absorption of the drug.
34. Cytarabine
• Cytarabine is a structural analogue of cytosine and is
phosphorylated intracellularly to the active triphosphate
form, which inhibits DNA polymerase.
• The triphosphate form also may be incorporated into DNA
to result in chain termination to prevent DNA elongation.
• The drug may be administered as a low-dose continuous
infusion, high-dose intermittent infusion, and into the
subdural space via intrathecal or intraventricular
administration.
• Cytarabine is eliminated by the kidneys with a renal
clearance of 90 mL/min (1.5 mL/s).
• Cytarabine has shown efficacy in the treatment of acute
leukemias and some lymphomas.
35. Cytarabine
• The toxicities of cytarabine in high doses include
myelosuppression; cerebellar syndrome (i.e., nystagmus,
dysarthria, and ataxia); and chemical conjunctivitis, an eye
irritation that requires prophylaxis with steroid eye drops.
• The risk of neurotoxicity is increased with high doses
(greater than 1 g/m2), advanced age, and renal
dysfunction.
• If cerebellar toxicity does occur, the drug needs to be
discontinued immediately, and decisions regarding further
therapy need to be carefully considered.
37. Mercaptopurine &Thioguanine
• 6-Mercaptopurine (6-MP) & thioguanine are oral purine
analogues that are converted to ribonucleotides that inhibit
purine synthesis.
• Mercaptopurine is converted into thiopurine nucleotides,
which are catabolized by thiopurine S-methyltransferase
(TPMT)
• Both of these agents are used in the treatment of acute
lymphocytic leukemia (ALL) and chronic myeloid leukemia
(CML).
• Because the agents are similar structurally, cross-
resistance is observed.
38. Mercaptopurine &Thioguanine
• Significant side effects include myelosuppression, mild
nausea, skin rash, cholestasis, and rarely, veno-occlusive
disease.
• Mercaptopurine is metabolized by xanthine oxidase, an
enzyme that is inhibited by allopurinol.
• This represents a major drug–drug interaction.
• To avoid toxicities of mercaptopurine when these drugs
are used concomitantly, the dose of mercaptopurine must
be reduced by 66% to 75%.
39. Antimetabolites: Folate
Antagonists
• Folates carry one-carbon groups in transfer reactions
required for purine and thymidylic acid synthesis.
• Dihydrofolate reductase is the enzyme responsible for
supplying reduced folates intracellularly for thymidylate
and purine synthesis.
• These include:
1. Methotrexate
2. Pemetrexed
3. Pralatrexate
40. Methotrexate
• Methotrexate inhibits dihydrofolate reductase of both
malignant and nonmalignant cells.
• When high doses of methotrexate are given, the “rescue
drug” leucovorin, a reduced folate, is administered to
bypass the methotrexate inhibition of dihydrofolate
reductase of normal cells and is usually initiated 24 hours
after methotrexate administration.
• This is done to prevent potentially fatal myelosuppression
and mucositis.
• High dosages of methotrexate may cause methotrexate to
crystallize out in the kidney, which may result in acute
renal failure & decreased methotrexate clearance.
41. Methotrexate
• Administration of IV hydration with sodium bicarbonate to
maintain urinary pH greater than or equal to 7 is necessary
to prevent methotrexate-induced renal dysfunction.
• Methotrexate is eliminated by tubular secretion; therefore,
concomitant drugs (eg, probenecid, salicylates, penicillin
G, and ketoprofen) that may inhibit or compete for tubular
secretion should be avoided.
• Methotrexate doses must be adjusted for renal dysfunction
and close monitoring of methotrexate concentrations is
advised.
• Side effects of methotrexate include myelosuppression,
nausea and vomiting, and mucositis.
43. Vinca Alkaloid
• The vinca alkaloids (vincristine, vinblastine,& vinorelbine)
are derived from the periwinkle (vinca) plant.
• They cause cytotoxicity by binding to tubulin, disrupting
the normal balance between polymerization and
depolymerization of microtubules,& inhibiting the assembly
of microtubules, which interferes with the formation of the
mitotic spindle.
• As a result, cells are arrested during the metaphase of
mitosis.
• The vinca alkaloids are used in several malignancies,
primarily hematologic.
• Even though these agents have similar structures, the
incidence and severity of toxicities vary among the agents.
44. Vinca Alkaloid
• The dose-limiting toxicity of vincristine is neurotoxicity,
which can consist of depressed tendon reflexes,
paresthesias of the fingers and toes, toxicity to the cranial
nerves, or autonomic neuropathy (constipation or ileus,
abdominal pain, and/or orthostatic hypotension.)
• In contrast, the dose-limiting toxicity associated with
vinorelbine and vinblastine is myelosuppression.
• All of the vinca alkaloids are vesicants and can cause
tissue damage; therefore, the clinician must take
precautions to avoid extravasation injury.
• Biliary excretion accounts for a significant portion of
elimination of vincristine and its metabolites, so doses
need to be adjusted for obstructive liver disease.
45. Vinca Alkaloid
• Vincristine, vinblastine, and vinorelbine have similar
sounding names, which is a potential cause of medication
errors.
• Unfortunately, vincristine has been involved in numerous
cases of fatal chemotherapy errors, including inadvertent
intrathecal administration.
• Because the drug is a vesicant, intrathecal administration
of the drug can cause widespread tissue damage in the
brain and death.
46. Taxanes
• Paclitaxel and docetaxel are taxane plant alkaloids that,
similar to the vinca alkaloids, exhibit cytotoxicity during the
M phase of the cell cycle by binding to tubulin.
• Unlike the vinca alkaloids, the taxanes do not interfere with
tubulin assembly.
• Rather, the taxanes promote microtubule assembly and
inhibit microtubule disassembly.
• Once the microtubules are polymerized, the taxanes
stabilize against depolymerization.
• Hepatic metabolism and biliary excretion account for the
majority of paclitaxel’s elimination.
47. Taxanes
Paclitaxel
• Hepatic metabolism and biliary excretion account for the
majority of paclitaxel’s elimination.
• Paclitaxel has demonstrated activity in several solid
tumors.
• The diluent for paclitaxel, Cremophor EL, is composed of
ethanol and castor oil.
• Patients receive dexamethasone, diphenhydramine, and
an H2 blocker to prevent hypersensitivity reactions caused
by Cremophor EL.
• Patients also may have asymptomatic bradycardia during
the infusion.
48. Taxanes
• Approximately 3 to 5 days after administration, patients
may complain of myalgias & arthralgias that may last
several days.
• Myelosuppression, flushing, neuropathy, ileus, and total-
body alopecia are other common side effects.
Nanoparticle Albumin-Bound Paclitaxel
• The nab-paclitaxel formulation uses nanotechnology to
combine human albumin with paclitaxel allowing for the
delivery of an insoluble drug in the form of nanoparticles.
• This unique formulation allows for an increased
bioavailability and higher intracellular concentrations of the
drug.
• There is also a significantly lower incidence of severe
neutropenia when compared to paclitaxel.
49. Taxanes
• The pharmacokinetics of the albumin-bound paclitaxel
displays a higher clearance and larger volume of
distribution than paclitaxel.
• The drug is eliminated primarily via fecal excretion.
• Bone marrow suppression, neuropathy, ileus, arthralgias,
& myalgias still occur.
50. Taxanes
Docetaxel
• Docetaxel has activity in the treatment of several solid
tumors also.
• Dexamethasone, 8 mg twice daily for 3 days starting the
day before treatment, is used to prevent the fluid-retention
syndrome associated with docetaxel and possible
hypersensitivity reactions.
• The fluid-retention syndrome is characterized by edema
and weight gain that is unresponsive to diuretic therapy
and is associated with cumulative doses greater than 800
mg/m2.
• Myelosuppression, alopecia, and neuropathy are other
side effects associated with docetaxel treatment.
51. Taxanes
Cabazitaxel
• Cabazitaxel is a newer taxane used in combination with
prednisone for the treatment of metastatic hormone-
refractory prostate cancer in patients previously treated
with a docetaxel containing treatment regimen.
• Cabazitaxel has shown to have similar adverse effects as
paclitaxel and docetaxel.
• Premedication with an antihistamine, corticosteroid, and
H2 antagonist to prevent hypersensitivity reactions is
required.
52. Topoisomerase Inhibitors
• Topoisomerase is responsible for relieving the pressure on
the DNA structure during unwinding by producing strand
breaks.
• Topoisomerase I produces single-strand breaks, whereas
topoisomerase II produces double-strand breaks.
• These include:
1. Epipodophyllotoxins (Etoposide & Teniposide)
2. Camptothecin Derivatives (Irinotecan & Topotecan)
53. Epipodophyllotoxins
(Etoposide and Teniposide)
• Etoposide & teniposide are semisynthetic podophyllotoxin
derivatives that inhibit topoisomerase II, causing multiple
DNA double-strand breaks.
• Etoposide has shown activity in the treatment of several
types of lymphoma, testicular and lung cancer,
retinoblastoma, and carcinoma of unknown primary.
• Oral bioavailability is approximately 50%, so oral dosages
are approximate 2 times those of IV doses.
• Teniposide has shown activity in the treatment of ALL,
neuroblastoma,& non-Hodgkin lymphoma.
• Both of these agents should be slowly administered to
prevent hypotension.
54. Epipodophyllotoxins
(Etoposide and Teniposide)
• Side effects of these agents include mucositis,
myelosuppression, alopecia, phlebitis, hypersensitivity
reactions, and secondary leukemias.
• Hypersensitivity reactions may be life threatening
55. Camptothecin Derivatives
(Irinotecan and Topotecan)
• Irinotecan & topotecan, both camptothecins, inhibit the
topoisomerase I enzyme to interfere with DNA synthesis
through the active metabolite SN38.
• Topoisomerase I enzymes stabilize DNA single-strand
breaks and inhibit strand resealing.
Irinotecan
• Irinotecan has shown activity in the treatment of cancers of
the colon, rectum, cervix, and lung.
• Irinotecan-induced diarrhea is a serious complication and
may be life threatening.
• One form of diarrhea (acute) can occur during or
immediately after the infusion.
56. Camptothecin Derivatives
(Irinotecan and Topotecan)
• This is a result of a cholinergic process in which the
patient may experience facial flushing, diaphoresis, &
abdominal cramping.
• IV atropine should be administered to treat diarrhea that
occurs any time during the first 24 hours of administration.
• Another form of diarrhea (chronic) can occur several days
after administration and can result in severe dehydration.
• This adverse effect should be treated immediately with
loperamide at a dosage of 2 mg every 2 hours or 4 mg
every 4 hours until diarrhea has stopped for 12 hours.
• Other side effects include myelosuppression, fatigue, and
alopecia.
57. Camptothecin Derivatives
(Irinotecan and Topotecan)
• Individuals homozygous for UGT1A1* have an increased
risk of febrile neutropenia and diarrhea and should be
considered for an empiric dose reduction of one level;
• Heterozygotes should receive closer monitoring, including
more frequent complete blood counts (CBCs) to detect
myelosuppression.
58. Camptothecin Derivatives
(Irinotecan and Topotecan)
Topotecan
• Topotecan has shown clinical activity in the treatment of
ovarian and lung cancer, myelodysplastic syndromes, and
AML.
• The IV infusion may be scheduled daily for 5 days or once
weekly.
• Side effects include myelosuppression, mucositis, and
diarrhea.
• Diarrhea is less common than with irinotecan.
60. Anthracene Derivatives
• Anthracyclines (daunorubicin, doxorubicin, idarubicin,&
epirubicin) are also referred to as antitumor antibiotics or
topoisomerase inhibitors when considering their
mechanism of action.
• All of the anthracyclines contain a four-membered
anthracene ring, a chromophore, with an attached sugar
portion.
• Free radicals formed from the anthracyclines combine with
oxygen to form superoxide, which can make hydrogen
peroxide.
• These agents are able to insert between base pairs of
DNA to cause structural changes in DNA.
61. Anthracene Derivatives
• However, the primary mechanism of cytotoxicity appears
to be the inhibition of topoisomerase II.
• These drugs are widely used in a variety of cancers.
• Oxygen-free-radical formation is a cause of cardiac
damage and extravasation injury, which is common with
these drugs.
• The anthracyclines can cause cardiac toxicity as
manifested by a congestive heart failure or
cardiomyopathy symptomatology, alopecia, nausea or
vomiting, mucositis, myelosuppression,& urinary
discoloration.
• These drugs are vesicants.
62. Anthracene Derivatives
• Dosage alterations should be made in the presence of
biliary dysfunction.
• To reduce the risk of cardiotoxicity associated with
doxorubicin, the maximum lifetime cumulative dose is 550
mg/m2.
• Ventricular ejection fractions should be measured before
therapy and periodically if therapy is continued.
• Therapy should be halted if there is a 10% to 20%
decrease from baseline in ejection fraction.
• Cardioprotectants (eg, dexrazoxane) have been used to
decrease risk in some cases.
63. Mitoxantrone
• This royal blue–colored drug is an anthracenedione that
inhibits DNA topoisomerase II.
• Mitoxantrone has shown clinical activity in the treatment of
acute leukemias, breast & prostate cancer, & non-Hodgkin
lymphomas.
• Myelosuppression, mucositis, nausea & vomiting, &
cardiac toxicity are side effects of this drug.
• Patients should be counseled that their urine will turn a
blue–green color.
64. Alkylating Agents
• Alkylating agents are the oldest class of anticancer drugs.
• The agents cause cytotoxicity via transfer of their alkyl
groups to nucleophilic groups of proteins and nucleic
acids.
• The major site of alkylation within DNA is the N7 position
of guanine, although alkylation does occur to a lesser
degree at other bases.
• These interactions can either occur on a single strand of
DNA (monofunctional agents) or on both strands of DNA
through a cross-link (bifunctional agents), which leads to
strand breaks.
• The major toxicities of the alkylating agents are
myelosuppression, alopecia, nausea or vomiting, sterility
or infertility, and secondary malignancies.
66. Nitrogen Mustards
(Cyclophosphamide and
Ifosfamide)
• Cyclophosphamide and ifosfamide are commonly used
bifunctional alkylating agents, therefore, causing cross-
linking of DNA.
• They each share similar adverse effects and spectrum of
activity, being used in a variety of solid and hematologic
cancers.
• Cyclophosphamide & ifosfamide are both prodrugs,
requiring activation by mixed hepatic oxidase enzymes to
get to their active forms, phosphoramide & ifosfamide
mustard, respectively.
67. Nitrogen Mustards
• During the activation process, additional byproducts
(acrolein & chloroacetaldehyde) are formed.
• Acrolein has no cytotoxic activity but is responsible for the
hemorrhagic cystitis associated with ifosfamide and high-
dose cyclophosphamide.
• Acrolein produces cystitis by directly binding to the bladder
wall.
• Prophylaxis is necessary with aggressive hydration,
administration of 2-mercaptoethane sulfonate sodium
(MESNA, which binds to and inactivates acrolein in the
bladder ), frequent voiding, and monitoring in patients
receiving ifosfamide and high-dose cyclophosphamide.
68. Busulfan
• Busulfan is an alkylating agent that forms DNA–DNA and
DNA–protein cross-links to inhibit DNA replication.
• Oral busulfan is well absorbed, has a terminal half-life of 2
to 2.5 hours, and is eliminated primarily by metabolism.
• It is also available in an IV formulation, which is useful
when using the high doses required in blood and marrow
transplantation.
• Busulfan has shown significant clinical activity in the
treatment of AML and CML and has been used as a
conditioning regimen prior to stem cell transplant.
• Side effects include bone marrow suppression;
hyperpigmentation of skin creases; & rarely pulmonary
fibrosis.
69. Busulfan
• High doses used for bone marrow transplant preparatory
regimens result in severe nausea and vomiting, tonic–
clonic seizures, & sinusoidal obstruction syndrome.
• Patients receiving high-dose busulfan should receive
anticonvulsant prophylaxis.
70. Heavy Metal Compounds
• Platinum drugs form reactive platinum complexes that bind
to cells.
• These include:
1. Cisplatin
2. Carboplatin
3. Oxaliplatin
71. Cisplatin
• Cisplatin forms inter- and intra-strand DNA cross-links to
inhibit DNA synthesis.
• Cisplatin has shown clinical activity in the treatment of
numerous tumor types, from head and neck cancers to
anal cancer, including many types of lymphoma and
carcinoma of unknown primary.
• Cisplatin is highly emetogenic and causes delayed nausea
& vomiting as well; patients require aggressive antiemetic
regimens for both delayed and acute emesis.
• Significant nephrotoxicity and electrolyte abnormalities can
occur if inadequate hydration occurs.
• Ototoxicity, which manifests as a high-frequency hearing
loss, and a glove-and-stocking neuropathy may limit
therapy.
72. Carboplatin
• Carboplatin has the same mechanism of action as
Cisplatin
• However, its side effects are similar but less intense than
those of cisplatin.
• Many chemotherapy regimens dose carboplatin based on
AUC, which is also called the Calvert equation.
• According to the Calvert equation, the dose in milligrams
of carboplatin = (CrCl + 25) × AUC desired, where CrCl is
expressed in mL/min.
• Carboplatin has shown clinical activity in the treatment of
several solid tumors and lymphoma.
• Thrombocytopenia, nausea and vomiting, and
hypersensitivity reactions are adverse effects.
73. mTOR Inhibitors
• The mammalian target of rapamycin (mTOR) is a
downstream mediator in the phosphatidylinositol 3-
kinase/Akt signaling pathway that controls translation of
proteins that regulate cell growth and proliferation but also
angiogenesis and cell survival.
• The mTOR is an intracellular component that stimulates
protein synthesis by phosphorylating translation
regulators, and contributes to protein degradation and
angiogenesis.
• These include:
1. Temsirolimus
2. Everolimus
75. Bleomycin
• Bleomycin is a mixture of peptides with drug activity
expressed in units, where 1 unit equals to 1 mg.
• Bleomycin causes DNA strand breakage.
• Bleomycin has shown clinical activity in the treatment of
patients with testicular cancer and malignant effusions,
squamous cell carcinomas of the skin, and Kaposi
sarcoma.
• Hypersensitivity reactions and fever may occur, so
premedication with acetaminophen may be required.
• The most serious side effect is the pulmonary toxicity that
presents as a pneumonitis with a dry cough, dyspnea,
rales, and infiltrates.
76. Bleomycin
• The pulmonary toxicity is potentiated by thoracic radiation
and by hyperoxia.
• Additional side effects include fever with or without chills,
mild to moderate alopecia, and nausea and vomiting.
77. Hydroxyurea
• Hydroxyurea is an oral drug that inhibits ribonucleotide
reductase, which converts ribonucleotides into the
deoxyribonucleotides used in DNA synthesis and repair.
• Hydroxyurea has shown clinical activity in the treatment of
CML, polycythemia vera, and thrombocytosis.
• The major side effects are myelosuppression, nausea &
vomiting, diarrhea, & constipation.
• Rash, mucositis, and renal tubular dysfunction occur
rarely.
78. L-Asparaginase
• L-Asparaginase is an enzyme that may be produced by
Escherichia coli.
• Asparaginase hydrolyzes the reaction of asparagine to
aspartic acid and ammonia to deplete lymphoid cells of
asparagine, which inhibits protein synthesis.
• L-Asparaginase has shown clinical activity in the treatment
of ALL and childhood AML.
• Severe allergic reactions may occur when the interval
between doses is 7 days or greater
• Pancreatitis and fibrinogen depletion may also occur
during therapy.
79. L-Asparaginase
• Repletion of fibrinogen should be done to prevent
disseminated intravascular coagulation and fatal bleeding.
• If the patient suffers an allergic reaction to L-asparaginase,
pegaspargase, which is L-asparaginase modified through
a linkage with polyethylene glycol, which extends the half-
life and allows for lower doses and less frequent
administration, may be given.
• Cost and limited availability are some reasons
pegaspargase may not be used first.
81. Interferons
• The categories of α, β, and γ interferons exist
• The α-interferons are used in the treatment of cancer.
• Interferon enhances the immune system’s attack on
cancer cells, can decrease new blood vessel formation,
and can augment expression of antigen on tumor cell
surfaces.
• Interferon has shown clinical activity in the treatment of
melanoma, kidney cancer, Kaposi sarcoma, and CML and
CLL.
82. Interferons
• Unfortunately, interferon is not well tolerated by patients
because it causes a flu-like syndrome that consists of
fevers and chills; depression, malaise, and fatigue are
other side effects.
• Premedication with acetaminophen helps alleviate the flu-
like symptoms, which decrease with chronic
administration.
83. Monoclonal Antibodies
• The cell surface contains molecules, which are referred to
as CD, which stands for “cluster of differentiation.”
• The antibodies are produced against a specific antigen.
• When administered, usually by an IV injection, the
antibody binds to the antigen, which may trigger the
immune system to result in cell death through
complement-mediated cellular toxicity, or the antigen–
antibody cell complex may be internalized to the cancer
cell, which results in cell death.
• Monoclonal antibodies also may carry radioactivity,
sometimes referred to as hot antibodies, and are referred
to as radioimmunotherapy, so the radioactivity is delivered
to the cancer cell.
84. Monoclonal Antibodies
• Antibodies that contain no radioactivity are referred to as
cold antibodies.
• All monoclonal antibodies end in the suffix -mab.
• The syllable before -mab indicates the source of the
monoclonal antibody.
• When administering an antibody for the first time, one
should consider the source.
• The less humanized an antibody, the greater the chance
for the patient to have an allergic-type reaction to the
antibody.
86. Monoclonal Antibodies
• The more humanized the antibody, the lower the risk of a
reaction.
• The severity of the reactions may range from fever and
chills to life-threatening allergic reactions.
• Premedication with acetaminophen and diphenhydramine
is common before the first dose of any antibody.
• If a severe reaction occurs, the infusion should be stopped
and the patient treated with antihistamines, corticosteroids,
or other supportive measures.
88. Tyrosine Kinase Inhibitors
• There are more than 100 different types of tyrosine
kinases present in the body.
• Tyrosine kinase inhibitors (TKIs) are also referred to as
small-molecule inhibitors.
• Each of the following drugs was developed to block either
several or a specific tyrosine kinase.
90. Hormonal Therapies
• A patient’s hormonal receptor status (eg, estrogen and
progesterone receptor status) can be used clinically as a
prognostic indicator & can help predict a response to
hormonal therapy.
• Hormonal or endocrine therapies have shown activity in
the treatment of cancers whose growth is affected by
gonadal hormonal control.
• Hormonal treatments either block or decrease the
production of endogenous hormones.
93. Antiandrogens: Bicalutamide,
Flutamide & Nilutamide
• The antiandrogens block androgen receptors to inhibit the
action of testosterone and dihydrotestosterone in prostate
cancer cells.
• Unfortunately, prostate cancer cells may become hormone
refractory.
• Side effects common to these agents are hot flashes,
gynecomastia, & decreased libido.
• Flutamide tends to be associated with more diarrhea and
requires three times daily administration, whereas
bicalutamide is dosed once daily.
94. Antiandrogens: Bicalutamide,
Flutamide & Nilutamide
• Nilutamide may cause interstitial pneumonia and is
associated with the visual disturbance of delayed
adaptation to darkness.
95. Aromatase Inhibitors
• There are 3 aromatase inhibitors (AI) currently available,
anastrozole, letrozole, & exemestane.
• Anastrozole and letrozole are selective nonsteroidal
aromatase inhibitor that lowers estrogen levels.
• Anastrozole is a standard adjuvant treatment of
postmenopausal women with hormone-positive breast
cancer.
• The length of therapy is usually 5 years; however,
evidence exists that suggests a benefit of prolonged
treatment in certain situations.
• Exemestane, a steroidal compound, is an irreversible
aromatase inactivator that binds to the aromatase enzyme
to block the production of estrogen from androgens.
96. Aromatase Inhibitors
• This difference in activity does not appear to translate into
improved clinical outcomes when compared to other AI
therapies.
• When compared to tamoxifen, there are less endometrial
and uterine cancers, vaginal bleeding, and thrombosis with
AI therapy.
• Common adverse effects associated with the AI therapy
include hot flashes and arthralgias.
• Serious adverse effects include osteoporosis, skeletal-
related events, and atherosclerotic cardiovascular disease.
• The AIs are used exclusively for postmenopausal women.
97. Antiestrogens
• Antiestrogens bind to estrogen receptors and block the
effect of estrogen on tissue.
• There are 2 classes of antiestrogens: selective estrogen-
receptor modulators (SERMs, tamoxifen, raloxifene) and
selective estrogen-receptor downregulators (SERDs,
Fulvestrant).
• SERDs were developed in an effort to eliminate the
unwanted estrogenic side effects from the SERMs.
98. Antiestrogens
• Tamoxifen is used for the treatment of estrogen receptor
(ER) positive premenopausal or postmenopausal
metastatic hormone receptor– positive breast cancer, as
adjuvant and primary treatment of breast cancer, and in
the prevention of breast cancer in high-risk women.
• It is associated with a significant decrease in disease
recurrence and mortality.
• The agent has a beneficial effect on bone density and the
lipid profile.
• Unwanted side effects include hot flashes, fluid retention,
& mood swings.
• Thrombosis, endometrial and uterine cancer, corneal
changes, and cataracts are harmful adverse effects that
occur more frequently with this agent.
99. Antiestrogens
• Although uncommon, there is a disease/tumor flare which
can occur during the initiation of therapy in metastatic
breast cancer patients with bone metastases.
• Because tamoxifen is a substrate of CYP3A4, decreased
tamoxifen levels have occurred with use of St. John’s wort
and rifampin.
100. Antiestrogens
• Raloxifene is another SERM and is used for the treatment
of osteoporosis in postmenopausal women and is the
chemopreventative agent of choice for the prevention of
breast cancer in high-risk women.
• Raloxifene was not studied in premenopausal women;
therefore, tamoxifen is still the preventative agent of
choice in these women.
• Hot flashes, arthralgias, & peripheral edema occur
frequently with raloxifene, but thrombosis and endometrial
cancer is less common than with tamoxifen.
101. Antiestrogens
• Fulvestrant is used as second-line treatment in hormone
receptor–positive metastatic breast cancer,
postmenopausal women with disease progression
following antiestrogen therapy.
• Fulvestrant is given as a monthly intramuscular injection,
which might be a deterrent to some patients.
• Other antiestrogen agents that are used in the treatment of
breast cancer include toremifene (SERM) and megestrol
acetate.
• Megestrol acetate can cause fluid retention, hot flashes,
vaginal bleeding and spotting, breast tenderness, and
thrombosis.
102. Administration Issues
Extravasation
• One issue of chemotherapy safety is extravasation.
• Antineoplastic agents that cause severe tissue damage
when they escape from the vasculature are called
vesicants.
• The tissue damage may be severe, with tissue sloughing
& loss of mobility, depending on the area of extravasation.
• Patients need to be educated to notify the nurse
immediately if there is any pain on administration.
• If extravasation of a vesicant occurs, the injection should
be stopped and any fluid aspirated out of the injection site.
103. Administration Issues
Hypersensitivity Reactions
• Hypersensitivity reactions of cancer treatments is
problematic because of cross-reactivity between agents
and the desire to continue active therapies against the
cancer.
• For documented immediate hypersensitivity reactions to a
particular agent, further administration of the agent may be
achieved through extensive premedication with H1 and H2
antihistamines and corticosteroids and through use of
escalating doses of the offending agent given at doses of
one-hundredth, one-tenth, and the balance of the dose (so
the total dose administered is equivalent to the normally
prescribed dose) administered over a much longer
104. Administration Issues
Secondary Malignancies
• Chemotherapy and radiation therapy treatments may
cause cancers later in life; these are referred to as
secondary cancers.
• The most common type of secondary cancer is
myelodysplastic syndrome, or AML.
• The antineoplastic agents most commonly associated with
secondary malignancies are alkylating agents, etoposide,
teniposide, topoisomerase inhibitors, & anthracyclines.
• Radiation therapy rarely may cause solid tumors as
secondary cancers decades after treatment e.g. breast
cancer, Hodgkin disease