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
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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.
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.
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.
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.
KeywordsCINV Pharmacokinetics Acute nausea and vomiting Delayed nausea and vomiting MEC
- 7.Hesketh PJ, Grunberg SM, Gralla RJ, Warr DG, Roila F, de Wit R, Chawla SP, Carides AD, Ianus J, Elmer ME, Evans JK, Beck K, Reines S, Horgan KJ (2003) The oral neurokinin-1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting: a multinational, randomized, double-blind, placebo-controlled trial in patients receiving high-dose cisplatin—the Aprepitant Protocol 052 Study Group. J Clin Oncol 21(22):4112–4119PubMedCrossRefGoogle Scholar
- 8.Poli-Bigelli S, Rodrigues-Pereira J, Carides AD, Julie Ma G, Eldridge K, Hipple A, Evans JK, Horgan KJ, Lawson F (2003) Addition of the neurokinin 1 receptor antagonist aprepitant to standard antiemetic therapy improves control of chemotherapy-induced nausea and vomiting. Results from a randomized, double-blind, placebo-controlled trial in Latin America. Cancer 97(12):3090–3098PubMedCrossRefGoogle Scholar
- 9.American Society of Clinical Oncology, Kris MG, Hesketh PJ, Somerfield MR, Feyer P, Clark-Snow R, Koeller JM, Morrow GR, Chinnery LW, Chesney MJ, Gralla RJ, Grunberg SM (2006) American Society of Clinical Oncology guideline for antiemetics in oncology: update 2006. J Clin Oncol 24(18):2932–2947PubMedCrossRefGoogle Scholar
- 16.Bécouarn Y, Ychou M, Ducreux M, Borel C, Bertheault-Cvitkovic F, Seitz JF, Nasca S, Nguyen TD, Paillot B, Raoul JL, Duffour J, Fandi A, Dupont-André G, Rougier P (1998) Phase II trial of oxaliplatin as first-line chemotherapy in metastatic colorectal cancer patients. Digestive Group of French Federation of Cancer Centers. J Clin Oncol 16(8):2739–2744PubMedGoogle Scholar
- 18.Arpornwirat W, Albert I, Hansen VL, Levin J, Bandekar RR, Grunberg SM (2009) Phase 2 trial results with the novel neurokinin-1 receptor antagonist casopitant in combination with ondansetron and dexamethasone for the prevention of chemotherapy-induced nausea and vomiting in cancer patients receiving moderately emetogenic chemotherapy. Cancer 115(24):5807–5816PubMedCrossRefGoogle Scholar
- 19.Hesketh PJ, Sanz-Altamira P, Bushey J, et al. Prospective evaluation of the incidence of delayed nausea and vomiting in patients with colorectal cancer receiving oxaliplatin-based chemotherapy. Poster presented at the 2008 ASCO Annual Meeting; June 2008; Chicago, ILGoogle Scholar
- 20.Rapoport BL, Jordan K, Boice JA, Taylor A, Brown C, Hardwick JS, Carides A, Webb T, Schmoll HJ (2010) Aprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with a broad range of moderately emetogenic chemotherapies and tumour types: a randomized, double-blind study. Support Care Cancer 18(4):423–431PubMedCrossRefGoogle Scholar
- 21.Herrstedt J, Apornwirat W, Shaharyar A, Aziz Z, Roila F, Van Belle S, Russo MW, Levin J, Ranganathan S, Guckert M, Grunberg SM (2009) Phase III trial of casopitant, a novel neurokinin-1 receptor antagonist, for the prevention of nausea and vomiting in patients receiving moderately emetogenic chemotherapy. J Clin Oncol 27(32):5363–5369PubMedCrossRefGoogle Scholar
- 22.Grunberg SM, Rolski J, Strausz J, Aziz Z, Lane S, Russo MW, Wissel P, Guckert M, Wright O, Herrstedt J (2009) Efficacy and safety of casopitant mesylate, a neurokinin 1 (NK1)-receptor antagonist, in prevention of chemotherapy-induced nausea and vomiting in patients receiving cisplatin-based highly emetogenic chemotherapy: a randomised, double-blind, placebo-controlled trial. Lancet Oncol 10(6):549–558PubMedCrossRefGoogle Scholar
- 23.Martin AR, Carides AD, Pearson JD, Horgan K, Elmer M, Schmidt C, Cai B, Chawla SP, Grunberg SM (2003) Functional relevance of anti-emetic control. Experience using the FLIE questionnaire in a randomised study of the NK-1 antagonist aprepitant. Eur J Cancer 39(10):1395–1401PubMedCrossRefGoogle Scholar
- 25.Martin AR, Cai B, Pearson J et al (2001) Patient-assessed impact of chemotherapy-induced nausea on daily life: how much is too much? Oncol Nurs Forum 28:338Google Scholar
- 26.Martin AR, Pearson J, Cai B et al (2002) Chemotherapy-induced nausea: VAS ratings <25 mm were predictive of patient reported outcomes. Proc Am Soc Clin Oncol 21:2918Google Scholar