Ramosetron Versus Ondansetron in Combination With Aprepitant and Dexamethasone for the Prevention of Highly Emetogenic Chemotherapy-Induced Nausea and Vomiting: A Multicenter, Randomized Phase III Trial, KCSG PC10-21

Oncologist. 2015 Dec;20(12):1440-7. doi: 10.1634/theoncologist.2015-0128. Epub 2015 Oct 28.

Abstract

Background: A combination of serotonin receptor (5-hydroxytryptamine receptor type 3) antagonists, NK-1 receptor antagonist, and steroid improves the complete response (CR) of chemotherapy-induced nausea and vomiting (CINV) in cancer patients. Ramosetron's efficacy in this triple combination regimen has not been investigated. This prospective, multicenter, single-blind, randomized, phase III study compares a combination of ramosetron, aprepitant, and dexamethasone (RAD) with a combination of ondansetron, aprepitant, and dexamethasone (OAD) to prove the noninferiority of RAD in controlling highly emetogenic CINV.

Methods: Aprepitant and dexamethasone were orally administered for both arms. Ramosetron and ondansetron were intravenously given to the RAD and OAD groups. The primary endpoint was no vomiting and retching and no need for rescue medication during the acute period (day 1); the noninferiority margin was -15%.

Results: A total of 299 modified intention-to-treat cancer patients who received RAD (144 patients) and OAD (155 patients) were eligible for the efficacy analysis. The CR rates of RAD versus OAD were 97.2% versus 93.6% during the acute period, 77.8% versus 73.6% during the delayed period (day 2-5), and 77.1% versus 71.6% during the overall period. Furthermore, RAD was noninferior to OAD in subgroups stratified by age, cancer type, chemotherapeutic agents, and schedule. Repeated measures analysis showed that in male patients, RAD was superior to OAD. Profiles of adverse events were similar in both groups.

Conclusion: RAD is as effective and tolerable as OAD for CINV prevention in patients receiving highly emetogenic chemotherapy. Ramosetron could be considered one of the best partners for aprepitant.

Keywords: Aprepitant; Chemotherapy; Nausea; Ondansetron; Ramosetron; Vomiting.

Publication types

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

MeSH terms

  • Aged
  • Antiemetics / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Aprepitant
  • Benzimidazoles / therapeutic use
  • Dexamethasone / therapeutic use
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Middle Aged
  • Morpholines / therapeutic use
  • Nausea / chemically induced
  • Nausea / drug therapy*
  • Neoplasms / drug therapy*
  • Ondansetron / therapeutic use
  • Prospective Studies
  • Single-Blind Method
  • Treatment Outcome
  • Vomiting / chemically induced
  • Vomiting / drug therapy*

Substances

  • Antiemetics
  • Benzimidazoles
  • Morpholines
  • Aprepitant
  • Ondansetron
  • Dexamethasone
  • ramosetron