Published on September 27, 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:
11. Biphasic pattern of emetic intensity
12. Acute phase Pathophysiology Delayed
13. WAYS REMEMBER DRUGS USED ARE A TEAM NOT COMPITITO
14. As regard aetiology:
15. RISK FACTORS FOR CINV
16. RISK FACTORS • PATIENT RELATED. • REGIMEN RELATED.
17. The most worrying Side effects of chemotherapy • Alopecia. • Vomiting. • Infection. • Nausea. • Weight loss.
18. Regimen related
19. Classification of regimens according to severity
20. Emetogenic potential of chemotherapeutic
21. 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.
22. OVERALL RISK= PATIENT RELATED RISK + REGIMEN RELATED RISK SO OVERALL RISK IS NEVER TO BE LESS THAN REGIMEN RELATED RISK
23. I’ll treat in the old school!
24. 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%
25. Highly emetogenic regimens 5HT-3 antagonist + Dexamethazone 75% of patients will experience CINV
26. moderately emetogenic regimens 5-HT3 antagonist + Dexamethazone 58% of patients will experience CINV
27. Long way !
28. Then came the Aprepitant era…
29. ESMO CLASSIFY MANAGEMENT OF CINV Before Aprepitant After Aprepitant
30. Then Phase III Studies… i.e. Compared to standard thx at that time
31. 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
32. 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 .
33. 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
34. 14 - 20% Absolute gain
35. GENERAL RULES OF MANAGEMENT
36. GUIDELINES !
37. Highly emetogenic Moderately emetogenic <24 h Acute >24 h delayed <24 h Acute >24 h delayed
38. ANTICIPATORY BREAKTHROUGHACUTEDELAYED LORAZEPAM PREMEDICATION PRESCRIPTION PRESCRIPTION
39. Casopitant • Nk1 antagonist. • GlaxoSmithKline decided to discontinue the regulatory filings for casopitant.
40. MASCC ESMO ASCO NCCN ONS Highly emetogenic Moderately emetogenic (Considered highly emetogenic) Other moderately emetogenic
41. 3 randomised controlled trials. granisterone + dexamethasone Rolapitant+ granisterone + dexamethasone
42. • 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.
43. 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.
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