This document discusses chemotherapy-induced nausea and vomiting (CINV). It provides background on the speaker's disclosures and affiliations. It then reviews the pathophysiology of CINV, risk factors, types of CINV, and the impact of inadequate CINV control on quality of life and treatment adherence. It discusses guidelines for preventing CINV and the efficacy of different antiemetic drugs, including 5-HT3 receptor antagonists, NK1 receptor antagonists, and steroids. It also reviews the evolution of CINV prevention over time with improved antiemetic regimens.
This simple and short PPT will review three international Guidelines; NCCN, ESMO and ASCO guidelines for emesis prevention when using I.V chemotherapeutic agents which are highly or moderately emetogenic.
Introduction to Targeted Therapies in OncologyMohamed Abdulla
Describes the molecular background which represents the core for developing targeted therapies against specific biological events in malignant cellular clones.
This simple and short PPT will review three international Guidelines; NCCN, ESMO and ASCO guidelines for emesis prevention when using I.V chemotherapeutic agents which are highly or moderately emetogenic.
Introduction to Targeted Therapies in OncologyMohamed Abdulla
Describes the molecular background which represents the core for developing targeted therapies against specific biological events in malignant cellular clones.
Chemotherapy induced Nausea and Vomiting
Professional and patient data
ارشادات للقئ والغثيان مع العلاج الكيمائي
Dr Salah Mabrouk Khallaf
د. صلاح مبروك خلاف
استشاري علاج الاورام
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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Antibody drug conjugates current status and future perspectivesPranav Sopory
ADC are an emerging class of new anti-cancer agents.
They are the future of oncological management.
Discussed here are their past, present and probable future.
Chemotherapy induced Nausea and Vomiting
Professional and patient data
ارشادات للقئ والغثيان مع العلاج الكيمائي
Dr Salah Mabrouk Khallaf
د. صلاح مبروك خلاف
استشاري علاج الاورام
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
Antibody drug conjugates current status and future perspectivesPranav Sopory
ADC are an emerging class of new anti-cancer agents.
They are the future of oncological management.
Discussed here are their past, present and probable future.
Presented at the American Society for Clinical Oncology Gastroenterology in January 2017 in San Francisco by Eric Raymond
Background: Sunitinib was approved by the FDA in 2011 for treatment of progressive, well-differentiated, advanced pancreatic neuroendocrine tumors (pNETs) based on a pivotal phase III study (NCT00428597) that showed a significant increase in progression-free survival (PFS) over placebo following early study termination. Subsequently, the FDA requested a post-approval study to support these findings.
Methods: In this open-label, phase IV clinical trial (NCT01525550), patients with progressive, well-differentiated, unresectable advanced/metastatic pNETs received continuous sunitinib 37.5 mg once daily. Eligibility criteria were similar to the phase III study. Primary endpoint was investigator-assessed PFS per RECIST 1.0. This study is ongoing.
Results: Sixty one treatment-naïve and 45 previously treated patients with progressive pNETs were treated with sunitinib: mean age, 54.6 years; males, 59.4%; white, 63.2%; ECOG PS 0, 65.1% or PS 1, 34.0%; and prior somatostatin analog, 48.1% (treatment-naïve, 39.3%; previously treated, 60.0%). At the data cutoff date, 82 (77%) patients discontinued treatment, mainly due to disease progression (46%). Median duration of treatment was ~11.9 months. Investigator-assessed median PFS (mPFS) was 13.2 months (95% CI, 10.9–16.7) in the overall population, with comparable mPFS in treatment-naïve and previously treated patients (13.2 vs 13.0 months). mPFS per independent radiologic review was 11.1 months (95% CI, 7.4–16.6). Objective response rate (ORR) per RECIST was 24.5%: 21.3% in treatment-naïve and 28.9% in previously treated patients. Median overall survival, although not yet mature, was 37.8 months. Treatment-emergent, all-causality adverse events (AEs) reported by ≥20% of all patients included neutropenia, diarrhea, leukopenia, fatigue, hand–foot syndrome, hypertension, abdominal pain, dysgeusia, and nausea. Most common grade 3/4 AEs were neutropenia (22%) and diarrhea (9%).
Conclusions: The mPFS of 13.2 months and ORR of 24.5% observed in this study support the outcomes of the pivotal phase III study of sunitinib in pNETs and confirm its activity in this setting. AEs were consistent with known safety profile of sunitinib.
Influence of anesthesia in oncological patientsJosef Saleh
Influence of antesthesia in oncological patients.
Anestesia en el paciente oncológico ¿Influye la técnica anestésica en la tasa de recidiva y en la supervivencia?
Roy H. Decker, MD, PhD, and Sarah B. Goldberg, MD, MPH, prepared useful practice aids pertaining to lung cancer for this CME activity titled "The Era of Immunotherapy in Stage III NSCLC: Exploring the Evidence and Practicalities of Integrating Checkpoint Inhibition Into the Multimodal Treatment Arsenal." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2PU3iaZ. CME credit will be available until December 6, 2019.
A Novel Immunohistochemical Signature with the Quantification of HER2 Predict...Premier Publishers
Around 30% of HER2-positive breast cancer patients do not respond to neoadjuvant chemotherapy (NAC) and anti-HER2 drugs. It is necessary to improve the selection system of patients who will benefit from this treatment, with others biomarkers that could also predict the response. HER2, ki67, ER, PR, LC45 and the HER family were quantified by immunochemistry in HER2+ breast tumors from 99 patients treated with NAC and anti-HER2 drugs. The correlation between the expression of these proteins and the response rate was evaluated through both an area under the ROC curve and a logistic regression model analysis. HER2 score 3+ is a poor predictive biomarker to NAC with anti-HER2 drugs, with an area under the ROC curve (AUCROC) HER2 score 3+ of 0.719. HER2 score 2+ with a curve of 0.438, is not associated with a response rate of treatment. The optimal HER2 score 3+ cutoff point has been proven to yield 21% in HER2-enriched tumors and 10% in HER2-luminal ones. The signature (AUC=0.809) formed by a high percentage of HER2 score 3+, a high percentage of Ki67, a low Histo-score of ER and the absence of involvement lymph nodes is a better predictive combination for response than HER2 score 3+ alone. HER2 status is a poor clinical biomarker. Our proposed signature will improve the selection of patients who benefit from the neoadjuvant treatment.
Chair, David M. O'Malley, MD, Ana Oaknin, MD, PhD, and Matthew A. Powell, MD, prepared useful Practice Aids pertaining to endometrial cancer for this CME/MOC/AAPA activity titled “Endometrial Cancer Care in the Age of Immunotherapy: Translating Clinical Evidence Into Meaningful Improvements in Patient Outcomes Across the Disease Continuum.” For the full presentation, downloadable Practice Aids, and complete CME/MOC/AAPA information, and to apply for credit, please visit us at https://bit.ly/40bmalK. CME/MOC/AAPA credit will be available until July 3, 2024.
Audio and slides for this presentation are available on YouTube: http://youtu.be/6W_xoH4s-Yk
Dr. Patrick Wen, of Dana-Farber Cancer Institute's Center for Neuro-Oncology, discusses current clinical trial options for brain tumor patients and some of the new therapies available in neuro-oncology. This presentation was originally given at Dana-Farber Cancer Institute on Dec. 4, 2013.
Similar to CINV (chemotherapy induced nausea & vomiting) (20)
Describes the emerging resistance of epithelial cancer of the ovary to current therapies and the role of PARP inhibitors in the management in view of the recent drug approvals.
Management of MSI High Solid Tumors and the impact of adding Immunotherapy upon improving survival outcome and response rate. Colorectal and Non Colorectal tumors.
Prostate cancer the androgenic fortified dogmaMohamed Abdulla
It describes the androgenic nature of prostate cancer and the androgenic axis should be tackled in all phases of prostate cancer. Also a special emphasis on recent data on management of metastatic hormone sensitive prostate cancer.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
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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
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.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
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
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
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
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
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
4. What Do Patients Receiving AC Based Cth Rate As the
Worst Side Effects?
*Other: eg, constipation, hypotension
Hernandez TC, et al. Support Care Cancer.
2015;23(11):3341-3359.
5. What Is the Real World Incidence of CINV With
"Optimal" Antiemetic Prescribing?
1. Dranitsaris G, et al. Ann Oncol. 2017;28(6):1260-1267. 2. Dranitsaris G, et al. Support Care
Cancer. 2016;24(4):1563-1569.
Grade 2
• Nausea: Reduced oral
intake, but no significant
weight loss, dehydration
or malnutrition
• Vomiting: 2-5 episodes in
24 hours
6.
7. CINV
The Problem:
Ineffective Control
or Persistent CINV
Quality of Life
Activities of
Daily Livings
Treatment
Outcome
Adherence
to Treatment
Schedule
Economic Burden
Hospital Stay
& Medical Care
1. Curran MP et al. Drugs. 2009;69(13):1853-78
2. Aapro M et al. Ann Oncol. 2012 Aug;23(8):1986-92. Epub 2012 Mar 6.
3. Janelsins MC et al. Expert Opin Pharmacother. 2013 April ; 14(6): 757–766.
4. Burke TA et al. Support Care Cancer. 2011 Jan;19(1):131-40.
10. CINV
Impact on Treatment Adherence & Survival:
P = .004
Neymark & Crott. Support Care Cancer
(2005) 13: 812–818
11. Chemotherapy-Induced Nausea and
Vomiting: Risk Factors
Patient-related risk factors1,2: Treatment-related risk factors:1,3
• Younger age (<50 years)
• History of Excessive alcohol and
tobacco use
• Susceptibility to motion sickness
• PriorCINV
• Anxiety
• Emesis during pregnancy
• Impaired performance status
• Previous exposure to chemotherapy
• Emetogenic potential of chemotherapy
agents or regimens (Hesketh classification)3
• Chemotherapy dose and schedule1
• Use of multiple chemotherapy agents3
1. Gregory RE, et al. Drugs. 1998;55(2):173-189. 2. Jordan K, et al. Oncologist. 2007;12(9):1143-1150. 3. Hesketh PJ,
et al. J Clin Oncol. 1997;15(1):103-109. 4. Janelsins MC, et al. Expert Opin Pharmacother. 2013; 14(6): 757-766.
12. CINV – Perception versus Reality:
Cumulative incidence of adverse symptom events over time as
reported by patients versus clinicians at
successive office visits
Basch E. N Engl J Med.
2010;362(10):865-869.
Months Months
*Patient-reported symptoms were collected directly from 467 persons with different malignant conditions at a total of 4034 clinic visits at
Memorial Sloan-Kettering Cancer Center, New York
**Clinician-reported symptoms were recorded by physicians and nurses treating those patients at the same visits
18. Is There an Optimal Regimen for Breast
Cancer Patients Receiving Anthracycline +
Cyclophosphamide?
• 47 antiemetic
regimens
• 15 CINV endpoints
• Heterogeneous
patient
populations,
chemotherapy, and
interventions
• All endpoint data not
available
• Cross trial
comparisons
difficult
Network diagram of
antiemetic regimens
Notes: Node size proportional to number of patients studied; line thickness
reflects number of trials
a, acute; d, delayed; OLANZ, olanzapine; STER,
steroids
Hutton B, et al. Cancer Treat Rev.
2015;41(10):951-959.
19. Effective Management of CINV:
1. Real perception of the problem & its
consequences.
2. Well orientation of risk factors.
3. Understanding the pathophysiology.
4. Anticipating the type of emesis.
5. Proper medical coverage.
6. Others to be considered.
20. Pathophysiology of CINV:
CPG
= VC
AP NTS CTZ
Enterochromaffin
Cells
D2
5-
HT3
NK1
Chemotherapy
5-
HT
5-
HT3
VagalAfferent
Gut Wall
Sub
P
Upper GIT
Emesis
Vagal Efferent
Higher Cortical Centers
Anticipatory
Vomiting
21. Receptors Implicated in Emetic Reflex:
Emetic
Reflex
Endorphins
Cannabinoids
Histamine
Acetylcholine
Serotonin
Substance P
Dopamine
GABA
22. Types of CINV:
Anticipatory Acute Delayed Breakthrough
Before and may be
after
0 – 12 Hour 24 – 96 Hr Any time and
persistent
Cognitive - Cortical H3 Receptors NK1 Psychological
Needs
Psychological
Support
Anti – H3 Anti-NK1 Problem
Tavorath R, Hesketh PJ. Drug treatment of chemotherapy-induced delayed emesis. Drugs 1996; 52:639.
Hesketh PJ, Sanz-Altamira P, Bushey J, Hesketh AM. Prospective evaluation of the incidence of delayed nausea and vomiting in
patients with colorectal cancer receiving oxaliplatin-based chemotherapy. Support Care Cancer 2012; 20:1043.
Morrow GR, Roscoe JA, Kirshner JJ, et al. Anticipatory nausea and vomiting in the era of 5-HT3 antiemetics. Support Care
Cancer 1998; 6:244.
23. Chemotherapy
Basch E, et al. J Clin Oncol. 2011;29(31):4198-4198, Roila F, et al. Ann Oncol. 2010;21(Suppl
5):v232-v243.
Risk Examples
High >90%
Cisplatin, streptozotocin,
carmustine, dacarbazine
Carboplatin, cyclophosphamide,
doxorubicin, ifosfamide, oxaliplatin,
irinotecan, alemtuzumab,
azacitidine, bendamustine
Etoposide, gemcitabine, 5FU,
docetaxel, paclitaxel,
cetuximab, panitumumab
Vinca alkaloids,
bleomycin, bevacizumab
Moderate
30%
to
90%
Low
10%
to
30%
Minimal <10%
Emetogenic Potential: IV Agents
24. Chemotherapy Risk Examples
High >90% Hexamethylmelamine, procarbazine
Roila F, et al. Ann Oncol. 2010;21(Suppl 5):v232-v243.
Moderate
30%
to
90%
Cyclophosphamide,
temozolomide, vinorelbine,
imatinib
Capecitabine, fludarabine,
etoposide, everolimus, lapatinib,
lenalidomide, sunitinib, thalidomide
Chlorambucil,
hydroxyurea, L-
phenylalanine mustard,
6-thioguanine, methotrexate,
gefitinib, erlotinib, sorafenib
Low
10%
to
30%
Minimal <10%
Emetogenic Potential: Oral Agents
“The antiemetic therapy for oral agents has to be individualized”
25. Patterns of emesis
Differences among antineoplastic agents
Cyclophosphamide/Carboplatin
Cisplatin
IntensityofEmesis
Acute phase
Days
Delayed phase
1. Martin M. Oncology. 1996;53(suppl 1): 26-31.
Different patterns of emesis induced by different antineoplastic drugs: to be considered
for CINV management in clinical practice
27. • 1198 patients enrolled in five non-interventional CINV
prospective studies
• 4197chemotherapy cycles
• http://www.riskcinv.org
Dranitsaris G, et al. Ann Oncol.
2017;28(6):1260-1267.
28. Chemotherapy Induced Nausea
and Vomiting
CINV can be prevented and should not
occur.
Use this tool to estimate your patient's risk (for
both acute and delayed CINV).
30. Questionnaire (Step
2 of 2)
1. Whatis the patient’s
gender?
2. What is the
patient’s age?
5.Doesthepatient expect
to devebp INV?
4. Did the patient have
morningsickness
e
More
Information
Referen
ces
Fem
ale
CIllV Risk
Assessment
5. Did the patient sleep 7 or
more hours
6.Afier the pevous cycH
ofcMmotherapy
(JapplrabH) dkJthpatient
take non- ant
7. Has the patient had any
nausea or a vomiting
episode in the priorcycle?
B.Is the chemotherapy
Anthracycline or
Pbtinum based?
Ye
s
Ye
s
31. Nausea: Reduced oral
intake, but no significant
weight loss, dehydration,
or malnutrition
Vomiting: 2-5 episodes in
24 hours
32. 49.8
°/‹
CINVRisk
EMETIC RISKGROUP ANTIEMETI
CS
SpecificRiskFactors: High NDn-AC 5-HT, + DEX N 1
• Age
• Anthracyclire-Dasedor Platinurfr
»•
5-HT,
Carboplatin 5-HT, + DEX + NK1
MDderate (other than
carboplatin)
5-HT, + DEX
LDW 5-HT, o
r
DEx or EN3P
Minimal No
routine prophylaxis
34. Steroids as Anti-emetics:
Mechanism of Action:
1. Anti-inflammatory effect.
2. Central interaction with NTS.
3. Interaction with Serotonin.
4. Interaction with NK1 Receptor.
5. Maintain organ physiology.
6. Regulate hypothalamic-Pituitary-Adrenal axis
7. Reducing pain and use of opiates.
Chu et al. Eur J Pharmacol. 2014 Jan 5;722:48-54
35. The Effect of Adding Dexamethasone
to 5-HT3 Antagonists on Acute
Emesis
P. 00001
antunen IT, et al. Eur J Cancer. 1997;33(1):66-74.
antunen IT, et al. Eur J Cancer. 1997;33(1):66-74.
36. Pharmacology
Chemical structure and main features of commonly used 5-HT3 RAs
1. Constenla, M. Ann Pharmacother. 2004;38(10):1683-1691. 2. Granisetron [prescribing information]. Heron Therapeutics, Inc. Redwood City,
CA; 2016. 3. Wong EH, et al. Br J Pharmacol. 1995;114(4):851-859. 4. Rojas C, et al. Anesth Analg. 2008;107(2):469-478. 5. Rojas C, et al. Eur J
Pharmacol. 2010;626(2-3):193-199. 6. Rojas C, et al. J Pharmacol Exp Ther. 2010. 335(2):362-368. 7. Saito M, et al. Lancet Oncol.
2009;10(2):115-124. 8. Janelsins MC, et al. Expert Opin Pharmacother. 2013;14(6):757-766.
PALO Ondansetron Granisetron
Half life (h)1 >40 5-6 Oral: 11.6, Subcu:
242
Binding affinity (pKi)3 10.45 8.39 8.91
Positive cooperativity4 YES NO NO
Inhibition of
receptor function5
Long
lasting
Short lasting Short lasting
Receptor
Internalization
YES NO NO
Inhibition of 5-HT3/NK1
receptor cross-talk6
YES NO NO
37. • Potent and selective NK1 RAs
• Competitively bind to and block activity of human SP receptors
• High binding affinity, differences in half-life (see also
fosaprepitant)
• High and long-lasting (for up to 96 hours) brain receptor
occupancy after single oral dose
• Influencing CYP3A4 (netupitant and (fos)aprepitant) or CYP2D6
(rolapitant)
1. Lorusso V, et al. Future Oncol. 2015;11(4):565-577. 2. Aprepitant [prescribing information]. Merck & Co., Inc.
Whitehouse Station, NJ; 2003. 3. Rizzi A, et al. Peptides. 2012;37(1):86-97. 4. Spinelli T, et al. J Clin Pharmacol.
2014;54(1):97-108. 5. Rolapitant [prescribing information]. TESARO, Inc. Waltham, MA; 2015. 6. Bernareggi A, et
al. Support Care Cancer. 2015;23(Suppl 1): Abstract 11-30-P. 7. Van Laere K, et al. Clin Pharmacol Ther.
2012;92(2):243-250.
PHARMACOLOGY
Main features of oral NK1RAs
Netupitant Aprepitant Rolapitant
Half-life (h) 961 9-132 169-1835
Binding Affinity
(pKi)
9.03 high2 high5
Striatum RO
reached at
120 hours
75%6 37-76%7 73%5
42. The Art of Today:
• Effective control of CINV is integral part of cancer
management nowadays.
• Effective control of CINV improves OAS.
• Risk model guiding the management is advisable and
coinciding with guidelines.
• 2nd Generation 5H3 blockers is much preferred than 1st
generation agents in terms of bioavailability,
pharmacodynamics and kinetics.
• Palonosetron is effective in controlling acute & delayed
CINV and is considered the backbone of any antiemetic
regimens.
• NK1 Receptor antagonist is more effective in delayed than
acute CINV and can be considered in addition to 5H3-RA in
certain patients and regimens
• Still Dexamethasone is added to most regimens.
43. To effectively control CINV;
Follow guidelines and Risk Stratification Models
Better than Expert judgment