This document discusses platinum hypersensitivity, including the case of a 60-year-old woman who experienced anaphylactic shock during carboplatin treatment for ovarian cancer. It outlines the mechanisms, incidence, and risk factors of platinum hypersensitivity reactions. It describes the different platinum agents (cisplatin, carboplatin, oxaliplatin) and approaches to address hypersensitivity reactions, including reducing infusion rates, premedication, switching agents, skin testing, and desensitization.
Please share this webinar with anyone who may be interested!
Watch all our webinars: https://www.youtube.com/playlist?list=PL4dDQscmFYu_ezxuxnAE61hx4JlqAKXpR
Cancer care is increasingly tailored to individual patients, who can undergo genetic or biomarker testing soon after diagnosis, to determine which treatments have the best chance of shrinking or eliminating tumours.
In this webinar, a pathologist and clinical oncologist discuss:
● how they are using these new tests,
● how they communicate results and treatment options to patients and caregivers, and
● how patients can be better informed on the kinds of tests that are in development or in use across Canada
View the video: https://youtu.be/_Wai_uMQKEQ
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Please share this webinar with anyone who may be interested!
Watch all our webinars: https://www.youtube.com/playlist?list=PL4dDQscmFYu_ezxuxnAE61hx4JlqAKXpR
Cancer care is increasingly tailored to individual patients, who can undergo genetic or biomarker testing soon after diagnosis, to determine which treatments have the best chance of shrinking or eliminating tumours.
In this webinar, a pathologist and clinical oncologist discuss:
● how they are using these new tests,
● how they communicate results and treatment options to patients and caregivers, and
● how patients can be better informed on the kinds of tests that are in development or in use across Canada
View the video: https://youtu.be/_Wai_uMQKEQ
Follow our social media accounts:
Twitter - https://twitter.com/survivornetca
Facebook - https://www.facebook.com/CanadianSurvivorNet
Pinterest - https://www.pinterest.com/survivornetwork
YouTube - https://www.youtube.com/user/Survivornetca
Pathomics Based Biomarkers and Precision MedicineJoel Saltz
Role of Digital Pathology Data Science (Pathomics) in precision medicine. Features from billions or trillions of objects segmented from digital Pathology data can be employed to predict patient outcome and steer treatment.
Presentation at Imaging 2020, Jackson Hole, WY September 2016
Randomized comparison of adjuvant aromatase inhibitor exemestane (E) plus ovarian function suppression (OFS) vs tamoxifen (T) plus OFS in premenopausal women with hormone receptor positive (HR+) early breast cancer (BC):
How can immunotherapy be used to treat metastatic breast cancer? Ian Krop, MD, PhD, discusses the latest research and treatment options.
This presentation was originally given as part of the 2015 Metastatic Breast Cancer Forum, held on October 17 and hosted by the Susan F. Smith Center for Women's Cancers at Dana-Farber Cancer Institute in Boston, Mass.
For more information, visit www.susanfsmith.org
Low dose Cancer Immunotherapy (Nivolumab) : Making immunotherapy affordable ...subhas123
Check point inhibitors are new immunotherapy drugs in market. However they are out of reach of most patient in low and middle income country due to high cost. Authors explored if Low-dose nivolumab can be effective in various cancers and the potential to put the expensive immunotherapy drug within reach of many more people with cancer, particularly in low- and middle-income countries. Low dose immunotherapy has been tried in various countries like belgium, south korea, singapore , taiwan and india and results have been generally good.
The efficacy of low-dose nivolumab and other immunotherapy drugs requires further study,
Management of locally advanced ovarian, fallopian tube, and peritoneal tumors requires a comprehensive and multidisciplinary approach. Locally advanced tumors are those that have spread beyond the ovaries or fallopian tubes and may involve nearby structures, such as the peritoneum or adjacent organs. Here's a brief overview of the management strategies:
Surgery:
Debulking Surgery: The primary treatment for locally advanced tumors involves cytoreductive or debulking surgery. This aims to remove as much of the tumor as possible. Surgeons may perform a total hysterectomy, bilateral salpingo-oophorectomy, and removal of involved peritoneal tissues.
Lymphadenectomy: Lymph node dissection is often done to assess the extent of the disease spread and to remove involved lymph nodes.
Chemotherapy:
Neoadjuvant Chemotherapy: In some cases, chemotherapy may be administered before surgery to shrink the tumor, making surgery more effective.
Adjuvant Chemotherapy: Following surgery, chemotherapy is typically recommended to target any remaining cancer cells. Platinum-based chemotherapy regimens are commonly used.
Targeted Therapies:
PARP Inhibitors: Poly (ADP-ribose) polymerase inhibitors, such as olaparib and niraparib, have shown efficacy in treating ovarian and related cancers with specific genetic mutations, like BRCA mutations.
Immunotherapy:
Checkpoints Inhibitors: Immune checkpoint inhibitors, like pembrolizumab and nivolumab, may be considered in cases with specific molecular profiles.
Radiation Therapy:
External Beam Radiation: In some situations, radiation therapy may be used to target specific areas affected by the tumor.
Clinical Trials:
Participation in clinical trials may be an option for patients with locally advanced disease, offering access to innovative treatments and therapies.
Follow-up Care:
Regular monitoring and follow-up care are crucial to assess treatment effectiveness and detect any signs of recurrence.
Palliative Care:
Palliative care should be integrated into the management plan to address symptom control, improve quality of life, and provide support for both the patient and their family.
A personalized treatment plan should be developed based on the specific characteristics of the tumor, the patient's overall health, and individual factors. Regular communication among a multidisciplinary team, including surgeons, medical oncologists, radiation oncologists, and other specialists, is essential for optimizing the management of locally advanced ovarian, fallopian tube, and peritoneal tumors.
Pathomics Based Biomarkers and Precision MedicineJoel Saltz
Role of Digital Pathology Data Science (Pathomics) in precision medicine. Features from billions or trillions of objects segmented from digital Pathology data can be employed to predict patient outcome and steer treatment.
Presentation at Imaging 2020, Jackson Hole, WY September 2016
Randomized comparison of adjuvant aromatase inhibitor exemestane (E) plus ovarian function suppression (OFS) vs tamoxifen (T) plus OFS in premenopausal women with hormone receptor positive (HR+) early breast cancer (BC):
How can immunotherapy be used to treat metastatic breast cancer? Ian Krop, MD, PhD, discusses the latest research and treatment options.
This presentation was originally given as part of the 2015 Metastatic Breast Cancer Forum, held on October 17 and hosted by the Susan F. Smith Center for Women's Cancers at Dana-Farber Cancer Institute in Boston, Mass.
For more information, visit www.susanfsmith.org
Low dose Cancer Immunotherapy (Nivolumab) : Making immunotherapy affordable ...subhas123
Check point inhibitors are new immunotherapy drugs in market. However they are out of reach of most patient in low and middle income country due to high cost. Authors explored if Low-dose nivolumab can be effective in various cancers and the potential to put the expensive immunotherapy drug within reach of many more people with cancer, particularly in low- and middle-income countries. Low dose immunotherapy has been tried in various countries like belgium, south korea, singapore , taiwan and india and results have been generally good.
The efficacy of low-dose nivolumab and other immunotherapy drugs requires further study,
Management of locally advanced ovarian, fallopian tube, and peritoneal tumors requires a comprehensive and multidisciplinary approach. Locally advanced tumors are those that have spread beyond the ovaries or fallopian tubes and may involve nearby structures, such as the peritoneum or adjacent organs. Here's a brief overview of the management strategies:
Surgery:
Debulking Surgery: The primary treatment for locally advanced tumors involves cytoreductive or debulking surgery. This aims to remove as much of the tumor as possible. Surgeons may perform a total hysterectomy, bilateral salpingo-oophorectomy, and removal of involved peritoneal tissues.
Lymphadenectomy: Lymph node dissection is often done to assess the extent of the disease spread and to remove involved lymph nodes.
Chemotherapy:
Neoadjuvant Chemotherapy: In some cases, chemotherapy may be administered before surgery to shrink the tumor, making surgery more effective.
Adjuvant Chemotherapy: Following surgery, chemotherapy is typically recommended to target any remaining cancer cells. Platinum-based chemotherapy regimens are commonly used.
Targeted Therapies:
PARP Inhibitors: Poly (ADP-ribose) polymerase inhibitors, such as olaparib and niraparib, have shown efficacy in treating ovarian and related cancers with specific genetic mutations, like BRCA mutations.
Immunotherapy:
Checkpoints Inhibitors: Immune checkpoint inhibitors, like pembrolizumab and nivolumab, may be considered in cases with specific molecular profiles.
Radiation Therapy:
External Beam Radiation: In some situations, radiation therapy may be used to target specific areas affected by the tumor.
Clinical Trials:
Participation in clinical trials may be an option for patients with locally advanced disease, offering access to innovative treatments and therapies.
Follow-up Care:
Regular monitoring and follow-up care are crucial to assess treatment effectiveness and detect any signs of recurrence.
Palliative Care:
Palliative care should be integrated into the management plan to address symptom control, improve quality of life, and provide support for both the patient and their family.
A personalized treatment plan should be developed based on the specific characteristics of the tumor, the patient's overall health, and individual factors. Regular communication among a multidisciplinary team, including surgeons, medical oncologists, radiation oncologists, and other specialists, is essential for optimizing the management of locally advanced ovarian, fallopian tube, and peritoneal tumors.
ASCO 2015 Melanoma Immunotherapy
Thomas Olencki, DO Division of Medical Oncology Department of Internal Medicine The Ohio State University Wexner Medical Center Columbus, Ohio
What’s the Latest in Clear Cell Ovarian Cancer?bkling
The understanding of clear cell ovarian cancer is evolving. If you’re diagnosed with clear cell ovarian cancer and eager for information specific to your subtype, we’ve got you covered! Join Dr. Jubilee Brown, Professor and Director of Gynecologic Oncology at Levine Cancer Institute, as she discusses current treatment options and any promising advances. Come with your questions and leave more informed about your subtype.
Arjun Balar, MD, and Petros Grivas, MD, PhD, prepared useful practice aids pertaining to bladder cancer management for this CME activity titled "Keeping Pace With Immunotherapy Advances in Bladder Cancer: Tools for Winning the Race and Optimizing Patient Outcomes." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2GpacAq. CME credit will be available until December 30, 2019.
Penicillin is drug of Choice for Syphilis- Still it holds good?inventionjournals
Syphilis resistant to Tetracyclins and macrolids had well documented. Penicillin is still considered as drug of choice in the treatment of Syphilis. Treponemes resistant to Penicillin are yet to be documented. In a private STD clinic of Tirunelveli, South India, during the period of January 2010 to June 2015, 68 cases reactive for syphilis were noted. 13.2 % of false positive were identified. Remaining 59 cases, 31 lost for follow up after treatment. Among whom 12 responded well to treatment following anti-syphilitic treatment with Penicillin whereas 16 (57.14%) remained reactive for more than a year or more. The titers either persist as same or even go up. Nobody in this group are reactive for HIV. All these patients remain in latent state in this series. Nobody progressed to neuro or cardiovascular syphilis. This warrants that it is high time to look for some other better alternative to treat Syphilis or otherwise increase in the dosage may have to be considered. Even though this study comprises of small number of patients, it has to be studied in detail for a longer period at multiple centers.
Penicillin is drug of Choice for Syphilis- Still it holds good?inventionjournals
Syphilis resistant to Tetracyclins and macrolids had well documented. Penicillin is still considered as drug of choice in the treatment of Syphilis. Treponemes resistant to Penicillin are yet to be documented. In a private STD clinic of Tirunelveli, South India, during the period of January 2010 to June 2015, 68 cases reactive for syphilis were noted. 13.2 % of false positive were identified. Remaining 59 cases, 31 lost for follow up after treatment. Among whom 12 responded well to treatment following anti-syphilitic treatment with Penicillin whereas 16 (57.14%) remained reactive for more than a year or more. The titers either persist as same or even go up. Nobody in this group are reactive for HIV. All these patients remain in latent state in this series. Nobody progressed to neuro or cardiovascular syphilis. This warrants that it is high time to look for some other better alternative to treat Syphilis or otherwise increase in the dosage may have to be considered. Even though this study comprises of small number of patients, it has to be studied in detail for a longer period at multiple centers.
Jorge A. Marrero, MD, MS, Anthony El-Khoueiry, MD, Richard S. Finn, MD, and Laura M. Kulik, MD, prepared useful practice aids pertaining to HCC management for this CME activity titled "Surveying the View From the Driver’s Seat in Hepatocellular Carcinoma: Bringing Into Focus Hepatology’s Key Role in Guiding HCC Care Down the Path to Improved Outcomes." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2Pj9wM8. CME credit will be available until December 20, 2019.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
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.
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
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.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
HOT NEW PRODUCT! BIG SALES FAST SHIPPING NOW FROM CHINA!! EU KU DB BK substit...GL Anaacs
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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.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
- 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
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 lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
4. Case
• นัดมาให้ PT regimen cycle 3 (10/7/62)
- Paclitaxel 260 mg in 5% D/W 500 ml in 3 hr ไม่มีอาการผิดปกติ
- Carboplatin 460 mg in 5% D/W 200 ml in 1 hr หลังให้ 15 นาที (54 ml) หน้าและแขนแดง คันที่
ปลายนิ้วมือ ไม่มีผื่น ไม่คัดจมูกหรือน้ามูกไหล แน่นอก อาเจียน ไม่ปวดท้อง ไม่มีไข้ T 36.7 BP 60/41 P 86 R 20
O2sat (RA) 90% L: clear Skin: flushing at face and forearms
Dx: Anaphylatic shock
Mx: Off Carboplatin, Adrenaline (1:1000) 0.5 ml IM*1 dose, CPM 10 mg IV, Ranitidine
50 mg IV, Dexamethasone 10 mg IV, NSS IV
หลังจากนั้น 10 นาที อาการดีขึ้น BP 140/75 P 80 O2 sat 100% จึง Admit observe
6. Introduction
• Chemotherapy including platinum agents is effective against a large number
of cancers and is used widely
• By forming crosslinks with DNA bases within cancer cells
• Platinum agents act to inhibit DNA replication
• This leads to suppression of division and proliferation of cancer cells, thus
killing these cells
Shingo M et al., Japanese Journal of Clinical Oncology, 2015, 45(9) 795–804
7. Introduction
• Widespread use of platinum
antineoplastic agents has led to an
increased incidence of
hypersensitivity reactions
• Allergic reactions can appear after a
significant number of infusions
with no prior clinical signs
• Carboplatin-based chemotherapy is
often administered over 6 cycles, and
hypersensitivity reactions are usually
observed during re-treatment, after a
period of remission
• Allergic crossreactivity between
cisplatin and carboplatin has been
reported, but the number of cases is
insufficient to establish the true
incidence
J.Boulanger et al, Curr Oncol, 2014, Vol.21, pp. e630-641
9. Cisplatin
• A first-generation platinum agent
• A non-natural compound
• Treatment be discontinued after a
maximum of 6 cycles when treating
non small cell lung cancer
Shingo M et al., Japanese Journal of Clinical Oncology, 2015, 45(9) 795–804
10. Carboplatin
• A second-generation platinum agent
• Can be administered to patients with reduced
kidney function
• It does not require large-volume transfusion
• It can be administered to outpatients
• In ovarian cancer, carboplatin is used as a
standard primary treatment
• In cases in which relapse occurs >6 months
following this primary treatment, retreatment
with carboplatin-containing chemotherapy
yields favorable results
Shingo M et al., Japanese Journal of Clinical Oncology, 2015, 45(9) 795–804
11. Oxaliplatin
• A third-generation platinum agent
• An integral drug used for colorectal
cancer and pancreatic cancer
• It is administered either until treatment
discontinuation due to toxicity or is
continually administered until
progression
• Increased frequency of cold-sensitive
dysesthesia and peripheral neuropathy
Shingo M et al., Japanese Journal of Clinical Oncology, 2015, 45(9) 795–804
12. Hypersensitivity Reactions (HSRs)
• An unforeseen reaction whose signs and symptoms cannot be explained by
the known toxicity of the drug
• Clinicians must choose whether to continue with the same treatment or to
suspend treatment and to search for other treatment options
• As continued readministration of these platinum agents contributes to
prolonged survival periods, clinicians contemplate rechallenge with these
platinum agents
Shingo M et al., Japanese Journal of Clinical Oncology, 2015, 45(9) 795–804
13. Approaches to Address HSRs
• Reducing the infusion rate
• Administering premedication
• Switching to a different platinum agent
• Skin testing
• Desensitization
Shingo M et al., Japanese Journal of Clinical Oncology, 2015, 45(9) 795–804
14. Mechanism
• Allergic reactions (Immunological mechanism)
• Non-allergenic (Cytokine release syndrome)
Shingo M et al., Japanese Journal of Clinical Oncology, 2015, 45(9) 795–804
16. Mechanism
• The mechanism has not yet been clearly elucidated
• Generally reported as immediate Type I allergies
• Mast cells and basophils react via IgE and release chemical messengers such
as histamine, leukotrienes and prostaglandins
• A variety of symptoms including anaphylaxis
Shingo M et al., Japanese Journal of Clinical Oncology, 2015, 45(9) 795–804
17.
18. October 1998-March 2003
126 patients
A total of 717 carboplatin skin tests (Median per patient 4 tests)
• Of the 668 negative tests (93% of
the total performed)
- 10 were associated with evidence of
carboplatin hypersensitivity (1.5%
false-negative rate; 95% CI, 0.6% to
2.4%), none of which were severe
• NPV 98.5%
• Of the 41 positive tests
- The decision was made to not deliver the
drug to 32 patients (7 patients ultimately
underwent a future attempt at re-treatment
with a platinum agent using a desensitization
program)
- In 7 episodes where patients received the
carboplatin despite the finding of a positive
test, 6 were associated with the development
of symptoms of anaphylaxis (none severe)
19.
20.
21. Mechanism
• Case reports present the possibility that cytotoxic (Type II) hypersensitivity
and immune complex (Type III) hypersensitivity contribute to HSRs to
platinum agents
• It has been suggested that cisplatin and carboplatin also induce Type IV
hypersensitivity through delayed T-cell sensitization
Shingo M et al., Japanese Journal of Clinical Oncology, 2015, 45(9) 795–804
22. Mechanism
• Santini et al. reported that 20 min following the administration of oxaliplatin,
cases with chills, stomach pain, diarrhea and fever showed increases in TNF-
α and IL-6, suggesting that oxaliplatin may act like a superantigen to
stimulate the release of these cytokines
Shingo M et al., Japanese Journal of Clinical Oncology, 2015, 45(9) 795–804
23. Incidence
• Immediate type hypersensitivity and asthma were occurring in workers at
platinum refinement plants who repeatedly inhale platinum-containing dust
• HSRs due to the use of anticancer agents have been reported since the
1970s
Shingo M et al., Japanese Journal of Clinical Oncology, 2015, 45(9) 795–804
24. Shingo M et al., Japanese Journal of Clinical Oncology, 2015, 45(9) 795–804
25. Risk Factors
• Risk factors of carboplatin HSRs:
- Age <70 years
- A history of allergies to environmental stimuli or drugs
- Administration with carboplatin at 650 mg or more
- A long platinum-free interval
Shingo M et al., Japanese Journal of Clinical Oncology, 2015, 45(9) 795–804
26.
27. Most patients who developed carboplatin HSR had a deleterious
BRCA1/2 mutation (93%) vs 50% in patients without HSR
(P<0.0001)
Mutation carriers had onset of carboplatin HSR at lower
cumulative exposure (P=0.003)
28. • Carboplatin may act as a hapten that
binds to serum proteins to elicit an
immunologic reaction
• Patients may be sensitised to the
protein–platinum adduct beginning
with the first-line treatment, with
immunologic restimulation during
subsequent regimens
• The DNA–platinum adduct itself may
be immunogenic
• Loss of normal BRCA function impairs
homologous recombination required for error-free
repair of DNA double-strand breaks that may
occur secondary to torsion caused by or excision of
interstrand platinum–DNA adducts
• Dysfunctional BRCA1 also disrupts nucleotide
excision repair, the mechanism through which
platinum adducts are repaired
• Impaired DNA repair may contribute to increase in
the DNA–platinum adducts, subsequently
augmenting exposure and possible HSRs to
carboplatin
29. Risk Factors
• The calypso study showed that hypersensitivity occurred more often among
patients receiving a carboplatin–paclitaxel combination than among those
receiving carboplatin combined with pegylated liposomal doxorubicin
(18.8% vs. 5.6%)
• Markman et al. showed that, compared with single-agent carboplatin, the
combination of pegylated liposomal doxorubicin and carboplatin reduced
the frequency of hypersensitivity reactions (0% vs. 30%)
J.Boulanger et al, Curr Oncol, 2014, Vol.21, pp. e630-641
30.
31. • It takes time to develop an allergy to platinum salts as has been seen with
increasing IgE antibodies over time in workers exposed to platinum salts
• However, that does not fully explain why a greater platinum-free interval
would expose a patient to a greater risk of HSR
• Sensitization or tachyphylaxis to the allergic effects of platinums occurs with
constant exposure and the increased time between retreatment reintroduces
sensitivity
32. Risk Factors
• The risk factors for the onset of HSRs to oxaliplatin:
- Young age
- Female gender
- Use of oxaliplatin as a second-line or higher therapy
• The total dose of oxaliplatin administered and oxaliplatin-free interval have
been reported to be associated with HSRs
Shingo M et al., Japanese Journal of Clinical Oncology, 2015, 45(9) 795–804
33. Symptoms and Signs
• Fever and/or shaking chills
• Cutaneous manifestations (80-90%)
• Gastrointestinal manifestations
• Respiratory manifestations
• Circulatory manifestations
• Most manifestations only mild to moderate
Shingo M et al., Japanese Journal of Clinical Oncology, 2015, 45(9) 795–804
34. Evaluation and Prevention:
Skin Test
• All patients receiving carboplatin be tested before each treatment after the 6th
cycle
• Patients who experience hypersensitivity symptoms and a positive skin-test
result should undergo a desensitization protocol
• Skin testing can be used to evaluate the potential for cross-reactions between
two platinum drugs
- Those with a positive result have a greater risk of experiencing cross-reactivity
between platinum salts
J.Boulanger et al, Curr Oncol, 2014, Vol.21, pp. e630-641
35. Evaluation and Prevention:
Infusion Time
• O’Cearbhaill et al. noted that administration of a 3-hour carboplatin infusion
together with premedication (instead of the standard 30-minute infusion)
could reduce the risk of hypersensitivity (3.4% vs. 21%)
J.Boulanger et al, Curr Oncol, 2014, Vol.21, pp. e630-641
36. Evaluation and Prevention:
Premedication
• Routine premedication with antihistamines and steroids is not recommended
before commencement of platinum-based therapy
• A small retrospective study showed that premedication (diphenhydramine,
dexamethasone, granisetron, and famotidine vs. dexamethasone and
granisetron) reduced hypersensitivity reactions associated with modified
folfox6 (leucovorin, 5-fluorouracil, oxaliplatin)
J.Boulanger et al, Curr Oncol, 2014, Vol.21, pp. e630-641
37. Treatment
• Early perception of changes in the patient’s condition
• The administration of drugs is then ceased
• Physiological saline
• A rapid evaluation of the patient’s circulation, airway, breathing, state of
consciousness and skin, oxygen
Shingo M et al., Japanese Journal of Clinical Oncology, 2015, 45(9) 795–804
38. Treatment
• Antihistamines alleviate symptoms such as itching, urticarial and angioedema
but have no life-saving effect
• Glucocorticoids may also alleviate delayed reactions, but the therapeutic
effects occur after some hours, and these drugs also have no life-saving effect
• Epinephrine is used as the primary treatment, particularly for anaphylaxis,
and an intramuscular injection of 0.1% (0.01 mg/kg) epinephrine (with a
maximum of 0.5 mg for adults) is given immediately to the anterolateral side
of the central thigh
Shingo M et al., Japanese Journal of Clinical Oncology, 2015, 45(9) 795–804
39. Treatment
• Extra attention should be paid to anaphylaxis cases in which biphasic
anaphylaxis may occur several hours after cessation of treatment and
resolution of symptoms
Shingo M et al., Japanese Journal of Clinical Oncology, 2015, 45(9) 795–804
40. Confounding Factors of Diagnosis of
HSRs to Platinum
• Patients receiving cancer therapy are prescribed many drugs that can cause
HSRs
• The cancer itself acts directly on mast cells to produce similar symptoms to
those of an HSR
• Several epidemiological studies have found that certain cancers have been
shown to increase the risk of allergies
• If possible, diagnosis may be made based on the results of skin or challenge
testing
Shingo M et al., Japanese Journal of Clinical Oncology, 2015, 45(9) 795–804
41. Desensitization
• The process in which the
concentration of an anticancer drug
acting as an antigen is increased in a
slow and step-wise manner to
induce a temporary tolerization state
toward the drug, until the target
dose is reached
• No standardized protocol for
desensitization
Shingo M et al., Japanese Journal of Clinical Oncology, 2015, 45(9) 795–804
42.
43.
44. Desensitization
• Increasing doses of the antigen are administered at fixed intervals
• Using this procedure in mouse bone marrow-derived mast cells sensitized to
IgE specific to antigens such as dinitrophenyl and ovalbumin, the release of
chemical mediators was suppressed
• The production of cytokines related to delayed onset reactions, like IL-6, was
also suppressed
Shingo M et al., Japanese Journal of Clinical Oncology, 2015, 45(9) 795–804
45.
46.
47.
48.
49.
50. • The same group reported alleviation of symptoms in 12 of 14 patients who had
HSRs during desensitization
• These patients were prescribed 325 mg of acetylsalicylic acid, a prostaglandin
blocker, and 10 mg of montelukast, a leukotriene blocker, both were administered 2
days prior to and on the day of desensitization
• The group on acetylsalicylic acid and montelukast showed a significant reduction in
symptoms compared with a historical control group using methylprednisolone as
premedication (0.5 mg/kg intravenous)
51.
52.
53.
54.
55.
56.
57. Recent HSR
(<3mo)
Remote HSR
(>9 mo)
Total Desensitization
ST positive 20 5 25 19
ST negative 4 9 13 11
Total 24 14 38 30
7/19 (37%)
had mild HSR
3/3 (100%) tolerated
a rapid protocol
without HSR and
remained ST negative
with repeated testing
6/8 (75%)
reacted during
desensitization
(More severe)
5/7 (71%) retested
became ST
positive before the
second
desensitization
58. Desensitization
• There have been few investigations of desensitization to oxaliplatin
• Many of these have a small number of cases
Shingo M et al., Japanese Journal of Clinical Oncology, 2015, 45(9) 795–804
59.
60. • Lee et al. conducted a retrospective analysis
of the results of 152 patients who had
experienced HSRs to oxaliplatin
• Undergone a premedication protocol with 20
mg of chlorpheniramine and 100 mg of
hydrocortisone given 1 h before
administration and/or desensitization
• The success rate of premedication alone in
patients who had severe HSRs was only
22.7%
• The success rate reached 86% when
desensitization was conducted
• XELOX regimen with a 3 week interval
was found to have a greater number of
administrations before the onset of an
initial HSR than FOLFOX regimen with a
2 week interval
• The actual time from the start of treatment
to the onset remained the same
• Rather than the number of administrations,
the length of treatment may be important
61. The Approach for HSRs during
Desensitization
• Discontinued
• Diphenhydramine or hydroxyzine
• If a severe reaction develops, oxygen and inhaled bronchodilators may be given
• H2-blockers and glucocorticoids are administered intravenously
• When necessary, epinephrine may also be considered
• Treatment may be restarted from where the desensitization process was interrupted,
with a reduced infusion rate or a reduced increment of dose
Shingo M et al., Japanese Journal of Clinical Oncology, 2015, 45(9) 795–804
62. Taxane Hypersensitivity
• Originally derived from the Pacific yew tree
• Disruption of microtubule function
• Whether hypersensitivity can be attributed to the taxanes themselves or to
their formulation vehicles has not yet been established
• Paclitaxel is administered in a solution of ethanol and Kolliphor EL
(formerly Cremophor EL)
• The reaction to docetaxel has been attributed to its vehicle, polysorbate 80
63. Taxane Hypersensitivity
• Risk factors:
- History of atopy
- History of mild skin reactions during earlier treatments
- The presence of respiratory dysfunction
- Overweight or obesity
- Menopausal or postmenopausal status
64. Taxane Hypersensitivity
• Paclitaxel and carboplatin are often administered concomitantly, and so it can
be difficult to distinguish which drug has triggered a hypersensitivity reaction
• Diagnosis is facilitated by the clinical presentation and the time of
appearance because the reactions are different for and specific to each agent
- Allergic reactions and anaphylaxis are caused by an immunological mechanism and HSRs occur within a relatively short time of the administration of the drug. Such HSRs are of the ‘immediate type’ and are classified as Gell and Coombs Type I allergies
- Cytokine release syndrome occurs due to the binding of the administered drug to circulating immune cells, such as monocytes and macrophages, causing the release of cytokines
- Aliquot ส่วนย่อย
- Markman 2003
- Patients and Methods:
Our group has used a predictive skin test in women with gynecologic cancers who have previously received more than 6 cumulative cycles of platinum-based chemotherapy.
30 minutes before all subsequent carboplatin courses, a 0.02-mL aliquot from the solution prepared for treatment is injected intradermally.
A positive test is considered to be a > 5-mm wheal, with a surrounding flare.
- Markman et al. reported skin testing as a useful method for predicting HSRs
- Zanotti 2001
- Patients and Methods:
Patients undergoing more than 7 courses of carboplatin received a 0.02-mL intradermal injection of an undiluted aliquot of their planned carboplatin infusion 1 hour before each course of the agent.
A positive skin test was prospectively defined as that resulting in a wheel of at least 5 mm with a surrounding flare.
We recently reported a 27% incidence of HRs in patients receiving more than 7 courses of carboplatin. These patients served as historical controls for the current study.
- Zanotti et al. also reported that, in a study of 47 patients, those who were negative for the intradermal reaction had a reduced risk of developing HSRs to carboplatin and had milder reactions even when HSRs did occur
- The HSR frequency increases with the number of carboplatin administrations
- It has been reported that HSRs occur in 1% of cases in which carboplatin is administered for 5 or fewer cycles, but they occur in as many as 27% of cases in which more than 7 cycles are administered
- Cisplatin:
Combination with radiation therapy increases the incidence of HSRs
- Oxaliplatin:
HSRs occur in 44% of cases using second and third-line therapies
The median time to the onset was 70 min
More severe HSRs occurred within 5–10 min from starting administration
- The incidence of HSRs to platinum agents increases as the number of administrations increases
- Deleterious เป็นอันตราย
- Moon 2013
- BCRA gene 1, 2=Breast cancer susceptibility gene 1, 2 เป็น Tumor suppressor gene ถ้ามี Mutation จะเพิ่ม Risk ของ Breast/ovary cancer
- Olaparib ยารักษามะเร็งรังไข่ที่มีการกลายพันธุ์ของยีน BRCA ในผู้ป่วยที่ตอบสนองต่อการรักษาด้วยยาเคมีบำบัดที่มี Platinum เป็นส่วนประกอบ
- Methods:
Medical records of women (ovarian cancer) enrolled in 2 carboplatin+olaparib clinical trials were reviewed.
A maximum of 8 cycles containing carboplatin were administered.
All women (N=87) had good performance status and end-organ function.
Incidences of carboplatin HSR before enrolment and on study were 17% and 21%, respectively.
- Adduct ดึงเข้าหากัน
- Augment เพิ่ม
- Suggests the possibility that liposomes have some impact on immune cells
- Schwartz 2006
- Schwartz et al. reported that the risk of a severe HSR to carboplatin was higher in the group in which the platinum-free interval was 2 years or more than in the group in which the interval was less than a year (47 vs. 6.5%)
- High-affinity IgE receptors on the surface of mast cells and basophils (FcεRI) act as key inducers of allergic reactions
- When re-exposed to the causative agent, drug-specific IgEs bound to FcεRI bind to the drug and, through crosslinking of IgE ให้ช้าๆเพื่อไม่ให้เกิด Crosslinking ของ FcεRI
- Castells 2008
- Methods:
98 patients who had HSRs in response to treatment with carboplatin, cisplatin, oxaliplatin, paclitaxel, liposomal doxorubicin, doxorubicin, or rituximab received rapid desensitization to these agents.
A standardized 12-step protocol was used, with treatment given intravenously or intraperitoneally.
Initial desensitizations occurred in the medical intensive care unit, whereas most subsequent infusions took place in an outpatient setting.
Safety and efficacy of the protocol were assessed by review of treatment records.
- 3 different concentrations of the solution were prepared
- Administered at 4 different infusion rates, with an administration time of 15 min for each step, except for the final step
- Total time 5.8 hr
- 65 patients had ovarian cancer
- 59 were desensitized to carboplatin
- HSRs occurred in 33% of cases (total 98 cases)
- Most of these were mild reactions and less severe than initial HSRs
- HSRs occurred in 51% of cases during the final step
- One patient required epinephrine
- All the cases completed the administration of carboplatin following recovery from their HSRs through appropriate medical treatment
- Lee 2005
- Lee et al. conducted a 12-step rapid desensitization in 31 cases that had experienced moderate-to-severe HSRs to carboplatin
- Methods:
A 3-solution, 12-step protocol delivered doubling drug doses by step, infusing the target dose over 5.8 h for inpatient and 3.8 h for outpatient administration.
- Total time 3.8 hr
- Undergo ได้รับ
- Hesterberg 2009
- Objectives:
To evaluate skin test (ST) reactivity to carboplatin in patients with recent and remote histories of carboplatin HSR
To review the relationship between skin test reactivity and tolerance of subsequent carboplatin desensitization.
- Methods:
38 women with carboplatin HSR were evaluated by ST to carboplatin.
30 women subsequently underwent 106 desensitizations to carboplatin.
- Total time 11 hr
- Conclusions:
The timing of carboplatin ST in relation to initial HSR is vital for risk stratification and subsequent desensitization.
Initial ST negative patients with a remote history of HSR are at high risk for conversion to ST positive and can develop more severe HSR.
Repeated skin testing was important in cases in which considerable time elapsed since their initial HSR
- Lee 2014
- Purpose:
This study investigated the characteristics of oxaliplatin-related hypersensitivity reactions (HSR).
Evaluated the efficacy of premedication and desensitization administration for controlling HSR in patients with gastrointestinal malignancy.
- Methods:
This retrospective study includes oxaliplatin hypersensitivity cases reported to our in-hospital, adverse drug reaction monitoring system between May 2008 and april 2012.
We analyzed administration histories of oxaliplatin and premedication treatments, chemotherapy cycle and severity of the initial HSR, and prophylactic measures and their outcomes in subsequent chemotherapy cycles.
- Oxaliplatin:
1. It is administered in combination with fluorouracil and leucovorin (FOLFOX regimen) for adjuvant chemotherapy in stage 3 colorectal cancer and for palliative chemotherapy in metastatic colorectal cancer
2. Or with capecitabine (XELOX regimen) for metastatic gastric or colorectal cancer therapy