cinv (chemotherapy induced nausea & vomiting)
TRANSCRIPT
Chemotherapy – Induced Nausea and Vomiting.
Case Presentation & Wrap Up
Mohamed Abdulla M.D.Prof. of Clinical Oncology
Cairo University
JW Marriott, CairoMundiPharma Stand Alone MeetingFriday, 11/03/2016
Disclosures:
Speaker, Consultant and Advisory Board Member for:• Amgen• Merck Serono• Janssen Cilag• Astra Zeneca• Pfizer• Astellas.• Hoffman La Roche• Novartis• Mundipharma
CINV:Overview:
Rank* 19831 19932 19953 19994 20045
1 Vomiting Nausea Nausea Nausea Fatigue
2 Nausea Constantly tired Loss of hair Loss of hair Nausea
3 Loss of hair Loss of hair Vomiting Constantly tired Sleep Disturbances
4Thought of coming for treatment
Effect on family Constantly tired Vomiting Weight loss
5 Length of time treatment takes Vomiting Having to have
an injectionChanges in the
way things taste Loss of hair
* In order of patients’relevance1. Coates A, et al. Eur J Cancer Clin Oncol. 1983;19:203-2082. Griffin AM, et al. Ann Oncol. 1996;7:189-1953. De Boer-Dennert M, et al. Br J Cancer. 1997;76:1055-10614. Lindley C, et al. Cancer Pract. 1999;7:59-655. Medscape CME
CINVThe Problem:
Ineffective Control or Persistent CINV
Quality of LifeActivities of Daily Livings
Treatment Outcome
Adherence to Treatment
Schedule
Economic BurdenHospital 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.
FLIE, Functional Living Index-EmesisLindley CM, et al. Qual Life Res. 1992;1(5):331-340; used with permission from Kluwer Academic Publishers ©1992.
80
70Patients experiencing CINV Patients without CINV
Mea
n FL
IE S
core
s
90
110
100
120 115
* 85
121
Before chemotherapy (day 1) After chemotherapy (day 3)
130 122(N = 122)
*P = .001
CINVImpact on Quality of Life:
CINVQoL & Physician’ Perception:
Does Not Fit with Health Care Providers’ Perception
Does Not Fit with Health Care Providers’ Perception
CINVQoL & Physician’ Perception:Total = 947
Physicians = 375
Nurses = 186
Patients =386
Vidall et al. Support Care Cancer (2015) 23:3297–3305
CINVImpact on Treatment Adherence & Survival:
EORTC RCT HEC Testis Ovary Lung
CINVImpact on Treatment Adherence & Survival:
P = .004
Neymark & Crott. Support Care Cancer (2005) 13: 812–818
Controlling Chemotherapy-Induced Emesis Progress Over the Past 30 Years:
Efficacy
1980 1990Cisplatin (highly emetic)
5-day complete control:
100% -
75% -
50% -
25% -
AC chemotherapy
0% 10%
50% 50%60% 50%
2000
85% 75%
2010
5-HT3 +steroids
Added NK1
AC, anthracycline–cyclophosphamide
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, panitumumabVinca alkaloids,
bleomycin, bevacizumab
Moderate 30% to
90%
Low 10% to
30%Minimal <10%
Emetogenic Potential: IV Agents
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, thalidomideChlorambucil,
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”
Patterns of emesisDifferences among antineoplastic agents
Cyclophosphamide/Carboplatin
CisplatinIn
tens
ity o
f Em
esis
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
Antiemetic Efficacy of Treatments Acute EmesisDelayed Emesis
Jordan K, et al. Crit Rev Oncol Hematol. 2007;61(2):162-175.
Mode of Action Class
5-HT3 receptor 5-HT3
antagonists (ondansetron, palonosetron)
NK1 antagonists (aprepitant, fosaprepitant)
Steroids Benzamides (metoclopramide)
Benzodiazepines
+++++++
+/-+/-+
++NK1 receptor
MultipleDopamine D2 receptor
GABA-chloride channelcomplexDopamine D2 receptor Multiple receptorsCB1-Receptor Muscarinic/ cholinergic rec.
+(+)(+)(+)
+(+)(+)(+)
Classical neuroleptics Olanzapine
Cannabinoids Antihistamine
s
(+)+
(+)−
(+)+
(+)−
Antiemetic Drugs
Binding Affinity of 5-HT3 Receptor Antagonists
1. Wong EH, et al. Br J Pharmacol. 1995;114(4):851-859. 2. van Wijngaarden I, et al. Eur J Pharmacol. 1990;188(6):301-312. 3. Miller RC, et al. Drug Dev Res. 1993;28(1):87-93.
5-HT3 Antagonist: pKi (nM):
Palonosetron1 10.4
Granisetron2 8.4
Ondansetron2 8.1
Dolasetron3 7.6
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.
Neurotransmitters, Antiemetics, and
Receptors- Acute Emesis: Moderate and High
Risk -
Setron >
Aprep>NK1
MCP >(In highDoses)
Serotonin
Substance P
Dopamine
5-HT3
D2
Aprep, aprepitant, MCP, metoclopramide
NEURON
NEPA + Dex*
80% 75% 90% 84%
Palonosetron + Dex* 72% 69% 72% 66%
Effectiveness of Netupitant + Palonosetron (“NEPA”) + DEX versus Palonosetron (“NEPA”) + DEX:
A Randomized Trial In 1450 Patients Receiving “AC” Chemo
* All regimen comparisons P≤.020
Aapro M, et al. Ann Oncol. 2014;25(7):1328-1333.
Observer Results Patient Reported Outcomes
No Emesis
No Nausea
No Impact on Daily Living: VOMITING
No Impact on Daily Living:
NAUSEA
• Female gender
• Young age
• Anxious personality• Minimal alcohol use (Caveat ≥5 drinks week
is protective)
• History of emesis during pregnancy
• History of motion sickness
• History of chemotherapy
Roila F, et al. J Clin Oncol. 1991;9(4):675-678. Morrow GR, et al. Support Care Cancer. 2002;10(2):96-105.
Individual Risk Factors
Not Taken into Considerations in Guidelines
More Than Chemicals Tricks Of The Trade
• What to eat or avoid: Flavors, odors, spicy foods
• Less quantity and more meal times• Hydration• Coca-Cola• Digipressure• Relaxation
Roles of Nurses
• Can help in guideline utilization if aware and understand the guidelines
• Lack of access to evidence-based medicine/nursing
• Position in institutions• Recognition of
education/competencies• Nurses-led clinics
Clinical Scenario :Anthracycline Chemotherapy
• 47-year-old woman with right sided 3 cm breast cancer– Grade 3 ER, 80%; Ki, 67%-30%– HER2 negative– 3/16 positive lymph nodes
• Recommended FE100C x 3 + docetaxel x 3 adjuvant chemotherapy– Hyperemesis in pregnancy– Normal LFTs and renal function
• Very fearful that vomiting will be severe
Please assume all agents are available and reimbursed…
1. Granisetron / ondansetron + dexamethasone2. Palonosetron + dexamethasone3. Aprepitant / fosaprepitant + 5-HT3 inhibitor + dexamethasone
4. NEPA (netupitant + palonosetron) + dexamethasone
*Plus rescue medication with PRN domperidone / metoclopramide / prochlorperazine
Which antiemetic regimen would you like to recommend for cycle 1*?
Take Home Message:
• Effective control of CINV is a pre-requisite in any cancer management.
• 5-H3 Receptor blockers are the cornerstone in management particularly Palonosetron.
• NK-1 Receptor Block: Mainly in HEC.• Role of Dexamethasone.• Combined Receptor Blockade.
Thank You