Prospective randomized comparison of tropisetron with and without dexamethasone against high-dose metoclopramide in prophylaxis of acute and delayed cisplatin-induced nausea and vomiting.

Abstract

Several studies have confirmed the efficacy of high-dose metoclopramide and, more recently, serotonin antagonists, with and without dexamethasone, in the prophylaxis of cisplatin-induced nausea and vomiting. Most of these trials have been reported from Western countries. There is little or no information about the efficacy and tolerability of these agents in ethnic groups in other countries. Furthermore, many patients in the developing countries cannot afford serotonin antagonists. The result is a critical need to evaluate these agents and justify their increasingly common use. The authors performed a prospective randomized trial to compare the efficacy and tolerability of tropisetron with and without dexamethasone against high-dose metoclopramide cocktail in patients receiving a uniform dose of cisplatin (100 mg/m2). Metoclopramide 2 mg/kg was combined with clemastine, dexamethasone, and lorazepam. These drugs were initially repeated at short intervals and subsequently given in the oral form for the next 5 days. Tropisetron 5 mg was administered intravenously 15 minutes immediately before cisplatin therapy and followed up with oral therapy for 5 days. The third group received the same doses of tropisetron along with dexamethasone before cisplatin and twice daily thereafter. The authors randomized 301 episodes. The patient characteristics were well balanced between the three groups. Acute nausea and vomiting were completely prevented in almost two thirds of patients receiving metoclopramide and tropisetron plus dexamethasone. These results are significantly superior to those of tropisetron alone (p < 0.01). Similarly, delayed nausea and vomiting were significantly better controlled with metoclopramdie cocktail and tropisetron plus dexamethasone than with tropisetron alone. Side effects were generally mild; however, they were more frequent with metoclopramide. The authors conclude that metoclopramide-based combination antiemetic therapy continues to be a cheaper alternative to serotonin antagonists and equally effective. Metoclopramide-based therapy, however, is more labor intensive, and issues related to administrative errors, side effects, and compliance gain increasing importance. The identification of persons at a higher risk for metoclopramide-induced side effects may help minimize the unacceptable consequences of therapy.