Evaluation of risk factors predictive of nausea and vomiting with current standard-of-care antiemetic treatment: analysis of two phase III trials of aprepitant in patients receiving cisplatin-based chemotherapy

Abstract

Certain patient and treatment characteristics are predictive of chemotherapy-induced nausea and vomiting (CINV). Objectives of this analysis were: (1) confirm the importance of several previously reported adverse risk factors for CINV in patients receiving chemotherapy, (2) assess the impact of the NK(1) receptor antagonist aprepitant according to these risk factors, and (3) assess the impact of age on antiemetic outcome. Patients from two double-blind, placebo-controlled trials were randomized to an active-control group (ondansetron 32 mg IV, dexamethasone 20 mg PO day 1; dexamethasone 8 mg bid days 2-4) or an aprepitant group (aprepitant 125 mg PO, ondansetron 32 mg IV, dexamethasone 12 mg day 1; aprepitant 80 mg days 2-3; dexamethasone 8 mg qd days 2-4). The primary endpoint was complete response (no emesis or rescue therapy use). In a post-hoc analysis, multivariate logistic regression models were used to assess the impact of treatment with aprepitant and previously reported risk factors, using a modified intent-to-treat approach. Treatment with aprepitant (p < 0.0001), male gender (p = 0.023), cisplatin dose <80 mg/m(2) (p = 0.001), age >or=65 years (p = 0.021), and five or more alcoholic drinks per week (p = 0.027) were all significantly associated with improved complete response. Aprepitant improved complete response regardless of risk for all factors and neutralized the risk associated with female gender. This analysis confirmed the relevance of several previously reported risk factors for CINV in patients receiving chemotherapy. Aprepitant improved complete response regardless of risk and eliminated the increased risk of CINV associated with the female gender.