Medline ® Abstracts for References 50,51
of 'Prevention and treatment of chemotherapy-induced nausea and vomiting in adults'
Single-dose intravenous casopitant in combination with ondansetron and dexamethasone for the prevention of oxaliplatin-induced nausea and vomiting: a multicenter, randomized, double-blind, active-controlled, two arm, parallel group study.
Hesketh PJ, Wright O, Rosati G, Russo M, Levin J, Lane S, Moiseyenko V, Dube P, Kopp M, Makhson A
Support Care Cancer. 2012 Jul;20(7):1471-8. Epub 2011 Aug 7.
PURPOSE: The primary objective was to determine if a single dose of casopitant 90 mg added to ondansetron and dexamethasone would improve the control of chemotherapy-induced nausea and vomiting (CINV) over 0-120 h following initiation of oxaliplatin-based moderately emetic chemotherapy (MEC) compared to ondansetron and dexamethasone alone.
METHODS: Patients with colorectal cancer received either casopitant or placebo intravenously (IV) added to ondansetron 8 mg bid oral on study days 1 to 3 and one dose of dexamethasone 8 mg IV given prior to starting the oxaliplatin on day 1. The primary endpoint was the percentage of subjects achieving complete response (CR; no vomiting/retching or use of rescue medication) during 120 h after initiation of chemotherapy in cycle 1.
RESULTS: No difference in the rate of CR was noted in the casopitant group compared to the placebo group for the overall (placebo 85%, casopitant 86%, p = 0.7273), acute (placebo 96%, casopitant 97%), or delayed phases (placebo 85%, casopitant 86%). The average area under curve (0-∞) of casopitant after a single 90-mg IV dose was 8,390 ng h/mL. At 24 h after casopitant 90-mg IV dosing, the plasma casopitant concentration was 24% lower than the values noted in prior studies with 150 mg oral administration, and the plasma exposure of the major metabolite (GSK525060) was 18% lower.
CONCLUSIONS: Addition of single-dose casopitant 90 mg IV did not improve the control of CINV at any time during 120 h following initiation of oxaliplatin-based MEC. Excellent control of CINV was achieved in this study population with the combination of ondansetron and dexamethasone alone.
Department of Hematology and Oncology, Lahey Clinic Medical Center, Burlington, MA 01805, USA. Paul.Hesketh@Lahey.org
Combination antiemetic therapy with aprepitant/fosaprepitant in patients with colorectal cancer receiving oxaliplatin-based chemotherapy (SENRI trial): a multicentre, randomised, controlled phase 3 trial.
Nishimura J, Satoh T, Fukunaga M, Takemoto H, Nakata K, Ide Y, Fukuzaki T, Kudo T, Miyake Y, Yasui M, Morita S, Sakai D, Uemura M, Hata T, Takemasa I, Mizushima T, Ohno Y, Yamamoto H, Sekimoto M, Nezu R, Doki Y, Mori M, Multi-center Clinical Study Group of Osaka, Colorectal Cancer Treatment Group (MCSGO)
Eur J Cancer. 2015 Jul;51(10):1274-82. Epub 2015 Apr 24.
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 theproportion 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.
Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka, Japan. Electronic address: firstname.lastname@example.org.