Combination antiemetic therapy with aprepitant/fosaprepitant in patients with colorectal cancer receiving oxaliplatin-based chemotherapy (SENRI trial): a multicentre, randomised, controlled phase 3 trial.

Abstract

INTRODUCTION:

The oral neurokinin-1 antagonist aprepitant is recommended in several guidelines for preventing chemotherapy-induced nausea & vomiting (CINV) due to highly emetogenic cancer chemotherapy. Little is known about the feasibility and safety of aprepitant in patients treated with oxaliplatin.

METHODS:

In this multicentre, open label, randomised, phase 3 trial, we recruited patients with colorectal cancer who underwent an oxaliplatin-based chemotherapy. Patients were centrally randomised in a 1:1 ratio to the control group (5-HT3-receptor antagonist+dexamethasone) or aprepitant group (5-HT3-receptor antagonist+dexamethasone+aprepitant or fosaprepitant) in the first course. All patients were treated with aprepitant/fosaprepitant therapy in the second course. The primary end-point was the proportion of patients with no emesis.

RESULTS:

A total of 413 patients entered this clinical trial from 25 centres in Japan. Significantly more patients in the aprepitant group achieved no vomiting overall and delayed phase than those in the control group (95.7% versus 83.6%, and 95.7% versus 84.7%, respectively). The aprepitant group also had statistically significantly higher percentages of no significant nausea, complete response and complete protection than the control group overall. In the control group, the percentages of no vomiting were higher in the second cycle than in the first cycle. The incidence of vomiting occurred day 7 or later was significantly higher in the control group compared with the aprepitant group. Other adverse events were not significant between the groups.

CONCLUSION:

The aprepitant therapy was more effective than the control therapy for prevention of CINV in colorectal cancer patients receiving an oxaliplatin-based regimen.

• Authors: Junichi Nishimura, Taroh Satoh, Mutsumi Fukunaga, Hiroyoshi Takemoto, Ken Nakata, Yoshihito Ide, Takayuki Fukuzaki, Toshihiro Kudo, Yasuhiro Miyake, Masayoshi Yasui, Shunji Morita, Daisuke Sakai, Mamoru Uemura, Taishi Hata, Ichiro Takemasa, Tsunekazu Mizushima, Yuko Ohno, Hirofumi Yamamoto, Mitsugu Sekimoto, Riichiro Nezu, Yuichiro Doki, Masaki Mori, Multi-center Clinical Study Group of Osaka, Colorectal Cancer Treatment Group (MCSGO)
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 51 Issue 10 Pg. 1274-82 (Jul 2015) ISSN: 1879-0852 [Electronic] England
• PMID: 25922233 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• Antiemetics
• Morpholines
• Organoplatinum Compounds
• Oxaloacetates
• Oxaliplatin
• Deoxycytidine
• Aprepitant
• Capecitabine
• fosaprepitant
• Leucovorin
• Fluorouracil

Topics

• Antiemetics (adverse effects, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects, therapeutic use)
• Aprepitant
• Capecitabine
• Colorectal Neoplasms (drug therapy)
• Deoxycytidine (administration & dosage, adverse effects, analogs & derivatives)
• Drug Therapy, Combination
• Female
• Fluorouracil (administration & dosage, adverse effects, analogs & derivatives)
• Humans
• Leucovorin (administration & dosage, adverse effects)
• Male
• Middle Aged
• Morpholines (adverse effects, therapeutic use)
• Nausea (chemically induced, prevention & control)
• Organoplatinum Compounds (administration & dosage, adverse effects)
• Oxaliplatin
• Oxaloacetates
• Vomiting (prevention & control)