Randomized, double-blind trial comparing the antiemetic effect of tropisetron plus metopimazine with tropisetron plus placebo in patients receiving multiple cycles of multiple-day cisplatin-based chemotherapy

Purpose: To compare the antiemetic efficacy and tolerability of tropisetron plus metopimazine with tropisetron plus placebo during 4 cycles of multiple-day, cisplatin-based chemotherapy. Materials and methods: 82 chemotherapy-naive patients with germ cell cancer scheduled to 4 cycles of multiple-day cisplatin-based chemotherapy (20 or 40 mg/m²/day for 5 days) given every 3 weeks were included. A double-blind parallel trial design was used and patients randomized to tropisetron plus metopimazine or tropisetron plus placebo. Tropisetron was administered as a single 5 mg intravenous dose on days 1-5 and a single 5 mg oral dose on day 6, and metopimazine as 30 mg orally t.i.d. on day 1, and q.i.d on days 2-6. Results: Patients were evaluable for efficacy during a total of 195 cycles. Small, but certain advantages were obtained with the combination. In cycle 1, complete protection from emetic episodes on day 1, days 1-5, days 6-9 and days 1-9 was achieved in 85.7%, 42.9%, 86.2% and 40.5% with tropisetron plus metopimazine and in 90.0%, 22.5%, 64.3% and 17.5% with tropisetron plus placebo, respectively. This difference achieved statistical significance in the overall period, days 1-9 (P=0.029). During the entire period (days 1-9), significantly less nausea was seen in patients receiving tropisetron plus metopimazine (P=0.027), whereas other nausea parameters did not reach statistical significance. The cumulative emetic protection rate after 4 cycles was 0.51 with tropisetron plus metopimazine and 0.25 with tropisetron plus placebo (P=0.037). Side effects were generally few and mild with both treatments and no significant differences were seen. Conclusion: Tropisetron plus metopimazine is superior to tropisetron during 4 cycles of multiple-day cisplatin-based chemotherapy, but both treatments are ineffective in a number of patients. The effect of the combination seems comparable to that of ondansetron plus dexamethasone. Newer drugs such as the neurokinin₁ receptor antagonist, aprepitant, should be investigated to optimize antiemetic therapy in patients receiving multiple-day chemotherapy.