Up-to-date pathophysiology and management of chemotherapy induced Nausea and vomiting in 2015

1. Thanks for your participation

2. UP-TO-DATE
MANAGEMENT OF
CHEMOTHERAPY
INDUCED NAUSEA
AND VOMITING
DR.TAREQ SALAH,MD
LECTURER OF CLINICAL ONCOLOGY
ASSIUT FCULTY OF MEDICINE
ESMO Accreditation certificate

3. Magnitude of the problem..

4. Everyday Case Scenario
• Female Patient,45 years old.
• Rt Breast cancer Stage II ,TNBC.
• Scheduled for adjuvant Chemotherapy 4AC—-12XP/w.
• Received Her 1st chemo 21 days ago and her 2nd chemotherapy is
today.
• She suffered considerable Nausea and vomiting after 2 days of the
first chemo that required ER admission and Intravenous fluids.
• Just upon entry to hospital she started to vomit.
• Is there a relation? Future management?

5. IMPORTANT
DEFINATIONS

6. TYPES OF CINV
Similar but not the same

7. TYPES OF CINV
• JUST TO MAKE IT SIMPLE..
TIMING AETIOLOGY
BREAKTHROUGHDELAYEDACUTE ANTICIPATORY

8. As regard Timing:

9. PATHOPHYSIOLOGY

10. Pathophysiology

11. Biphasic pattern of emetic intensity

13. Acute
phase
Pathophysiology
Delayed

15. WAYS REMEMBER DRUGS USED ARE A TEAM NOT COMPITITO

16. As regard aetiology:

17. RISK FACTORS FOR
CINV

18. RISK FACTORS
• PATIENT RELATED.
• REGIMEN RELATED.

20. The most worrying Side
effects of chemotherapy
• Alopecia.
• Vomiting.
• Infection.
• Nausea.
• Weight loss.

21. Regimen related

22. Classification of regimens
according to severity

23. Emetogenic potential of chemotherapeutic

29. Other factors
few studies have accounted for important treatment-
and patient-related variables, such as
• Chemotherapy dose.
• Dose Rate .
• Route of administration.
• Gender.
• Age .
• History of ethanol consumption.

30. OVERALL RISK=
PATIENT RELATED
RISK
+ REGIMEN RELATED RISK
SO OVERALL RISK IS NEVER TO BE LESS THAN REGIMEN RELATED RISK

31. I’ll treat in the old school!

32. Tumor Type
emetogenic
chemotherapy
Incidence of nausea
and vomiting
Lung cancer
Gemcitabine/Caroplatin
Paclitaxel/Carboplatin
Docitaxel/Carboplatin
69%
59%
42%
Lymphoma CHOP 50%
Colon
FOLFOX4
FOLFIRI
65%
50%
Breast
TC
AC
14%
42%
Risk of CINV
30-90%

33. Highly emetogenic regimens
5HT-3 antagonist + Dexamethazone
75% of patients will experience CINV

34. moderately emetogenic regimens
5-HT3 antagonist + Dexamethazone
58% of patients will experience CINV

35. Long way !

36. Then came the Aprepitant
era…

38. ESMO CLASSIFY MANAGEMENT OF CINV
Before Aprepitant After Aprepitant

39. Then Phase III Studies…
i.e. Compared to standard thx at that time

40. Standard
Experimental
Day 1 Day 2,3,4
ondansetron 32 mg+
dexamethasone 20
mg
dexamethasone 8 mg
twice a day on days 2–
4 +
ondansetron 32 mg
aprepitant 80 mg on
days 2 and 3
+ dexamethasone 8
mg daily on days
2–4
aprepitant 125 mg
on day 1+
Dexamethasone 12
mg

41. The dexamethasone dose was reduced in the
aprepitant arms because a pharmacokinetic study
found that aprepitant increased dexamethasone
plasma concentrations resulting in an approximately
twofold increase in AUC .

42. The primary endpoint was complete response (no
emesis, no use of rescue antiemetics) over the 5-day
study period.
In all three studies complete response was
significantly superior with aprepitant (73% versus
52%, P < 0.001; 63% versus 43%, P < 0.001; 72%
versus 61, P < 0.003).
ESMO GL 2010

43. 14 - 20%
Absolute
gain

45. GENERAL RULES
OF MANAGEMENT

46. GUIDELINES !

47. Highly emetogenic Moderately emetogenic
<24 h
Acute
>24 h
delayed
<24 h
Acute
>24 h
delayed

52. ANTICIPATORY BREAKTHROUGHACUTEDELAYED
LORAZEPAM PREMEDICATION
PRESCRIPTION
PRESCRIPTION

56. Casopitant
• Nk1 antagonist.
• GlaxoSmithKline decided to discontinue the
regulatory filings for casopitant.

57. MASCC ESMO ASCO NCCN ONS
Highly
emetogenic
Moderately
emetogenic
(Considered
highly
emetogenic)
Other
moderately
emetogenic

59. 3 randomised controlled trials.
granisterone + dexamethasone
Rolapitant+ granisterone + dexamethasone

60. • Rolapitant inhibits the CYP2D6 enzyme.
• Rolapitant is contraindicated with the use of
thioridazine because use of the 2 drugs
together may increase the amount of
thioridazine in the blood and cause an abnormal
heart rhythm that can be serious.
• The most common side effects in patients
treated with rolapitant include neutropenia,
hiccups, decreased appetite, and dizziness.

61. Take home message
• CINV is very worrying side effect.
• Best management is prevention from the start.
• It is a standard in highly emetogenic
chemotherapy regimens.(+AC).
• ? in moderately emetogenic regimens and not in
mildly emetogenic chemotherapy.
• Not in mild or minimal emetogenic.