A systemic review and meta analysis of Aprepitant Combination Regimens (ACR) for prevention of Chemotherapy induced Nausea

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1 A systemic review and meta analysis of Aprepitant Combination Regimens (ACR) for prevention of Chemotherapy induced Nausea and Vomiting (CINV) in adults Fahad Zubair, PGY 3 UB CHS Internal Medicine

2 Nausea and vomiting are devastating side effects of treatment with antineoplastic agents. CINV can lead to conditioning after repeated cycles of therapy. Metabolic imbalances. Degeneration of self care and functional ability. Anorexia Mental status, wound dehiscence and esophageal tears.

3 Expert Opin Pharmacother. Author manuscript; available in PMC 2014 Feb 28.Published in final edited form as: Expert Opin Pharmacother Apr; 14(6): doi: /

4 Management Dopamine receptor blockers, serotonin receptor antagonists and steroids help. Unfortunately the effectiveness of these drugs remained largely limited to acute emesis even when started before the first dose of the anticancer drug at each cycle of treatment. Theroleofcurrentlyavailabledrugsinthemanagement of delayed emesis (occurring after 24 h) is very less.

5 Drugs which block substance P from binding to neurokinin type 1 (NK 1 ) receptors can be used as antiemetic agents as these neurotransmitters are implicated in the pathophysioology of emesis. Aprepitant is the first member of this new class of antiemetic drugs.

6 Navari, R. Chemotherapy induced Nausea and Vomiting, 1st edition. Oxford University Press: 2010

7 Intoduction Various randomized controlled trials (RCTs) have shown improved outcomes with addition of Aprepitant to standard antiemetic treatment (SAT) for preventing CINV in adults. We conducted a systematic review and meta analysis to study the overall impact of Aprepitant in CINV prevention.

8 Methods Search to retrieve articles was conducted in Pubmed and Ovid databases, and American Society of Clinical Oncology meetings proceedings. Nausea, vomiting, chemotherapy, aprepitant. Search included RCTs that studied aprepitant combinationwithsatforpreventionofcinvinadult cancer patients.

9 Primary end point: Complete response to treatment (CR; defined as no emesis and no use of rescue medications): 1) In the overall phase (OP; hrs of chemotherapy), 2) In the acute phase (AP; 0 24 hrs), and 3) In the delayed phase (DP; hrs).

10 In addition to CR, we also assessed control of nausea in each phase, use of rescue medications in each phase and toxicity profile (TP). Stouffer's Z score method used to test for overall effect.

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16 Conclusion ACR is effective in CINV due to both HEC and MEC in adult cancer patients. ACR improves the complete response (control of emesis without any rescue therapy) in all phases. ACR improves nausea only in delayed phase.

17 Overall toxicity profile of Aprepitant Combination Regimens are similar to Standard antiemetic treatment. (except fatigue, hiccups, neutropenia). Aprepitant Combination Regiments cause more fatigue & hiccups, and lesser neutropenia.

18 Addition of Aprepitant to SAT should routinely be done in patients undergoing highly or moderately emetogenic chemotherapy.

19 Future research considerations Exploring ACR in treatment of CINV, in addition to prevention of CINV. Exploring other Neurokinin 1 antagonist like casopitant in prevention and treatment of CINV.

20 References Navari RM: Management of chemotherapy induced nausea and vomiting : focus on newer agents and new uses for older agents. Drugs 73:249 62, 2013 Navari RM, Gray SE, Kerr AC: Olanzapine versus aprepitant for the prevention of chemotherapy induced nausea and vomiting: a randomized phase III trial. J Support Oncol 9:188 95, 2011 Roscoe JA, Heckler CE, Morrow GR, et al: Prevention of delayed nausea: a University of Rochester Cancer Center Community Clinical Oncology Program study of patients receiving chemotherapy. J Clin Oncol 30: , Kris MG. Why do we need another antiemetic? Just ask. J Clin Oncol 2003;21: The national comprehensive cancer network. Clinical practice guidelines. Antiemesis, version Available from: [Last accessed on 2005 Jun 1] Rittenberg CN. A new class of antiemetic agents on the horizon. Clin J Oncol Nurs 2002;6:103 4.

21 Thank you Dr. Gupta Dr. Srivastava Dr. Qazi Dr. Woodman