Association of Aprepitant and Palonosetron in Prevention of Acute and Delayed Nausea and Vomiting in High Emetogenic Chemotherapy Regimens

Abstract

ABSTRACT Aim: The recently published Multinational Association of Supportive Care in Cancer (MASCC) and European Society of Medical Oncology (ESMO) guidelines in the prevention of nausea and vomiting, recommended the use of aprepitant, dexametasone, and a serotonin antagonist (5HT3 receptor antagonist), to prevent nausea and vomiting in high emetogenic chemotherapy (HEC) schedules, although there is debate on which should be the ideal 5HT3 antagonist. Many studies have compared palonosetron with ondansetron and granisetron in the prevention of cisplatin-induced acute nausea and vomiting. The complete response was similar in the first 24 hours, but significantly superior with palonosetron on days 2–5, and on days 1–5, suggesting that palonosetron induced more protection from delayed emesis before HEC. The aim of our study is to test the efficacy of the concomitant use of palonosetron and aprepitant in preventing nausea and vomiting in HEC. Methods: We analyzed data collected from 100 consecutive patients who received HEC chemotherapy between April 2013 and May 2014 at our Institute, with various schedules for different type and stage of disease. Patients were pretreated with an antiemetogenic schedule consisting in aprepitant (oral 125 mg, on day one; oral 80 mg, on days 2 and 3), palonosetron (i.v. 0.25 mg, on day 1), and dexametasone (i.v. 12 mg, on day 1). Nausea and vomiting were classified as acute phase (within 24 hours from infusion) or delayed phase (days 2 to 5), and intensity of disorder was classified according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) criteria, version 4.0. Data were collected at baseline and every cycle of therapy. Results: Day 1 complete response was 84.9%, while complete response from days 2 to 5 was 79.5%. Outcome for complete protection, total control, no vomiting, no nausea were respectively 61.2%, 52.9%, 90.3% and 53.6% for acute phase, and 54.7%, 43.2%, 89.2% and 43.9% for the delayed phase. Most reported side effect were hiccups, fatigue, constipation, headache and anorexia; no serious adverse event was reported. Conclusions: Association of aprepitant and palonosetron is an effective prophylaxis of acute and delayed emesis, with no serious toxicity reported. Phase 3 trials to compare different 5HT3 antagonists are warranted to clarify the best antiemetogenic strategy. Disclosure: All authors have declared no conflicts of interest.