Multicenter, phase II, placebo-controlled, double-blind, randomized study of aprepitant in Japanese patients receiving high-dose cisplatin

Aprepitant is a new neurokinin-1 (NK1) receptor antagonist developed as a treatment for chemotherapy-induced nausea and vomiting (CINV). To evaluate the efficacy and safety of aprepitant used in combination with standard therapy (granisetron and dexamethasone), we conducted a multicenter, phase II, placebo-controlled, double-blind, randomized study in Japanese cancer patients who received cancer chemotherapy including cisplatin (>= 70 mg/m2). Aprepitant was administered for 5 days. A total of 453 patients were enrolled. In the three study groups, (i) standard therapy, (ii) aprepitant 40/25 mg (40 mg on day 1 and 25 mg on days 2-5) and (iii) aprepitant 125/80 mg (125 mg on day 1 and 80 mg on days 2-5), the percentage of patients with complete response (no emesis and no rescue therapy) was 50.3% (75/149 subjects), 66.4% (95/143 subjects) and 70.5% (103/146 subjects), respectively. This shows that efficacy was significantly higher in the aprepitant 40/25 mg and 125/80 mg groups than in the standard therapy group (chi 2 test [closed testing procedure]: P = 0.0053 and P = 0.0004, respectively) and highest in the aprepitant 125/80 mg group. The delayed phase efficacy (days 2-5) was similar to the overall phase efficacy (days 1-5), indicating that aprepitant is effective in the delayed phase when standard therapy is not very effective. In terms of safety, aprepitant was generally well tolerated in Japanese cancer patients. (ClinicalTrials.gov number, NCT00212602.) (Cancer Sci 2010; 101: 2455-2461).