how to manage chemotherapy induced nausea and vomiting

1. Chemotherapy – Induced
Nausea and Vomiting.
Case Presentation & Wrap Up
Mohamed Abdulla M.D.
Prof. of Clinical Oncology
Cairo University
JW Marriott, Cairo
MundiPharma Stand Alone Meeting
Friday, 11/03/2016

2. Disclosures:
Speaker, Consultant and Advisory Board Member for:
• Amgen
• Merck Serono
• Janssen Cilag
• Astra Zeneca
• Pfizer
• Astellas.
• Hoffman La Roche
• Novartis
• Mundipharma

3. 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
4
Thought of
coming for
treatment
Effect on family Constantly tired Vomiting Weight loss
5
Length of time
treatment takes
Vomiting
Having to have
an injection
Changes in the
way things taste
Loss of hair
* In order of patients’relevance
1. Coates A, et al. Eur J Cancer Clin Oncol. 1983;19:203-208
2. Griffin AM, et al. Ann Oncol. 1996;7:189-195
3. De Boer-Dennert M, et al. Br J Cancer. 1997;76:1055-1061
4. Lindley C, et al. Cancer Pract. 1999;7:59-65
5. Medscape CME

4. 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.

5. FLIE, Functional Living Index-Emesis
Lindley CM, et al. Qual Life Res. 1992;1(5):331-340; used with permission from Kluwer Academic Publishers ©1992.
80
70
Patients experiencing CINV Patients without CINV
MeanFLIEScores
90
110
100
120
115
*
85
121
Before chemotherapy (day 1) After chemotherapy (day 3)
130
122(N = 122)
*P = .001
CINV
Impact on Quality of Life:

6. CINV
QoL & Physician’ Perception:
Does Not Fit with Health
Care Providers’ Perception
Does Not Fit with Health Care
Providers’ Perception

7. CINV
QoL & Physician’ Perception:
Total =
947
Physicians =
375
Nurses =
186
Patients =
386
Vidall et al. Support Care Cancer (2015) 23:3297–3305

8. CINV
Impact on Treatment Adherence & Survival:
EORTC RCT
HEC
Testis Ovary Lung

9. CINV
Impact on Treatment Adherence & Survival:
P = .004
Neymark & Crott. Support Care Cancer
(2005) 13: 812–818

10. Controlling Chemotherapy-Induced
Emesis Progress Over the Past 30 Years:
Efficacy
1980 1990
Cisplatin (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

12. 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

13. 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”

14. 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

15. Antiemetic Efficacy of Treatments
Acute Emesis Delayed
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
Multiple
Dopamine D2 receptor
GABA-chloride channel
complex
Dopamine D2 receptor
Multiple receptors
CB1-Receptor Muscarinic/
cholinergic rec.
+(+)
(+)
(+)
+(+)
(+)
(+)
Classical neuroleptics
Olanzapine
Cannabinoids
Antihistamines
(+)
+
(+)
−
(+)
+
(+)
−
Antiemetic Drugs

16. 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

17. 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.

18. Neurotransmitters,
Antiemetics, and
Receptors
- Acute Emesis: Moderate and High
Risk -
Setron>
Aprep> NK1
MCP >
(In high
Doses)
Serotonin
Substance P
Dopamine
5-
HT3
D2
Aprep, aprepitant, MCP,
metoclopramide
NEURON

19. 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

20. • 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

22. 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

23. 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

24. 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

25. Please assume all agents are available and reimbursed…
1. Granisetron / ondansetron + dexamethasone
2. Palonosetron + dexamethasone
3. 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*?

26. 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.

27. Thank You