Comparison of the efficacy of tropisetron versus a metoclopramide cocktail based on the intensity of cisplatin-induced emesis.

Abstract

Cisplatin-induced emesis is one of the most feared side effects in cancer treatment. High-dose metoclopramide may prevent only 30-40% of cases of acute emesis. Investigations to test the efficacy of new antiemetics are mandatory. We compared the efficacy, toxicity, and patients' preference for tropisetron, a new 5-hydroxytryptamine3 (HT3) receptor antagonist, with those of a combination of high-dose metoclopramide, dexamethasone, diphenhydramine, and lorazepam (metoclopramide cocktail) in a randomized crossover study for the control of nausea and vomiting during cisplatin-containing chemotherapy. A total of 62 chemotherapy-naive women were included and followed over 3 consecutive courses. Detailed analysis comparing the incidence of acute emesis for each 4 h period following cisplatin infusion was also performed. Complete protection from acute emesis was obtained in 48% of patients receiving tropisetron and 29% of patients receiving the metoclopramide cocktail over the first two courses of chemotherapy (P = 0.029). When the frequency of acute emesis in all patients was compared on a daily basis, no significant difference was found. When emesis frequency was compared over each 4 h period following infusion of cisplatin, tropisetron was superior to the metoclopramide cocktail during the first, the second, and the first and second periods (P = 0.0001, P = 0.01 and P = 0.0006, respectively). This superiority reversed after 12 h but did not reach statistical significance (P = 0.112). Tropisetron was more effective in controlling acute nausea, but metoclopramide provided better control of delayed emesis. A drop in efficacy over successive courses was observed in patients receiving metoclopramide first but was not seen in tropisetron-first patients. A tendency for tropisetron preference was observed. Tropisetron is more effective than the metoclopramide cocktail in the control of chemotherapy-induced vomiting within 8 h of the implementation of cisplatin and in the control of nausea on the 1st day. To improve the control of chemotherapy-induced emesis, further investigations on the additional tropisetron dosing at 8 h after cisplatin infusion or the combination use of tropisetron and other antiemetics by a continuous 4 h period of observation and comparison are mandatory.