Aprepitant versus metoclopramide, both combined with dexamethasone, for the prevention of cisplatin-induced delayed emesis: a randomized, double-blind study

Ann Oncol. 2015 Jun;26(6):1248-1253. doi: 10.1093/annonc/mdv132. Epub 2015 Mar 5.

Abstract

Background: A combination of aprepitant, a 5-HT3 receptor antagonist (r.a.), and dexamethasone is recommended for the prophylaxis of cisplatin-induced nausea and vomiting in the acute phase, and aprepitant + dexamethasone (A + D) in the delayed phase. The aim of this study was to verify if A + D is superior to metoclopramide plus dexamethasone (M + D) in preventing delayed emesis in cancer patients receiving the same prophylaxis for acute emesis.

Patients and methods: A randomized double-blind study comparing A + D versus M + D was completed in previously untreated cancer patients. Before chemotherapy, all patients were treated with intravenous palonosetron 0.25 mg and dexamethasone 12 mg, and oral aprepitant 125 mg. On day 2-4, patients randomly received oral dexamethasone 8 mg plus aprepitant 80 mg once daily (days 2-3) or metoclopramide 20 mg four times daily plus dexamethasone 8 mg bid. Primary endpoint was rate of complete response (no vomiting, no rescue treatment) in day 2-5 after chemotherapy.

Results: Due to difficulty in the accrual of patients, 303 of the 480 planned patients were enrolled, 284 were fully evaluable, 147 receiving A + D, 137 M + D. Day 1 results were similar in both arms. On day 2-5, complete response rate was not significantly different (80.3% with A + D versus 82.5% with M + D, P < 0.38, respectively), and all secondary endpoints were also similar (complete protection, total control, no vomiting, no nausea, and score of Functional Living Index-Emesis; P < 0.24). Adverse events incidence was not significantly different between the two treatments.

Conclusions: In cancer patients submitted to cisplatin-based chemotherapy, receiving the same antiemetic prophylaxis for acute emesis, A + D is not superior to M + D in preventing delayed emesis, and both treatments present similar toxicity.

Clinicaltrialsgov number: NCT00869310.

Keywords: aprepitant; cisplatin; delayed emesis; metoclopramide.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activities of Daily Living
  • Administration, Intravenous
  • Administration, Oral
  • Adolescent
  • Adult
  • Aged
  • Antiemetics / administration & dosage*
  • Antiemetics / adverse effects
  • Antineoplastic Agents / adverse effects*
  • Aprepitant
  • Cisplatin / adverse effects*
  • Dexamethasone / administration & dosage*
  • Dexamethasone / adverse effects
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Combinations
  • Female
  • Humans
  • Isoquinolines / administration & dosage
  • Italy
  • Male
  • Metoclopramide / administration & dosage*
  • Middle Aged
  • Morpholines / administration & dosage*
  • Morpholines / adverse effects
  • Nausea / chemically induced
  • Nausea / prevention & control*
  • Nausea / psychology
  • Palonosetron
  • Quality of Life
  • Quinuclidines / administration & dosage
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Vomiting / chemically induced
  • Vomiting / prevention & control*
  • Vomiting / psychology
  • Young Adult

Substances

  • Antiemetics
  • Antineoplastic Agents
  • Drug Combinations
  • Isoquinolines
  • Morpholines
  • Quinuclidines
  • Aprepitant
  • Palonosetron
  • Dexamethasone
  • Metoclopramide
  • Cisplatin

Associated data

  • ClinicalTrials.gov/NCT00869310