Antiemetic Efficacy of High-Dose Metoclopramide: Randomized Trials with Placebo and Prochlorperazine in Patients with Chemotherapy-Induced Nausea and Vomiting

In a study of the effectiveness of high intravenous doses of metoclopramide as an antiemetic, 41 patients with advanced cancer who were being treated with cisplatin were entered into two double-blind trials. In the first trial patients were randomly assigned to receive either metoclopramide or placebo, and in the second trial they received either metoclopramide or prochlorperazine. Patients given metoclopramide had significantly fewer episodes of emesis than patients given placebo (medians, 1.0 vs. 10.5; P = 0.001) or prochlorperazine (medians, 1.5 vs. 12.0; P = 0.005). Metoclopramide was superior to placebo and to prochlorperazine in reducing the volume of emesis (P = 0.001 and P = 0.022, respectively) and was more effective than placebo in shortening the duration of nausea (P = 0.042) and vomiting (P = 0.028). Side effects from metoclopramide were minor, with mild sedation frequently observed; one patient had a brief extrapyramidal reaction. We conclude that metoclopramide in high intravenous doses has greater antiemetic activity than placebo or prochlorperazine in patients receiving cisplatin chemotherapy. (N Engl J Med. 1981; 305:905–9.). NAUSEA and vomiting remain the most frequent and debilitating acute side effects of chemotherapy for advanced cancer. Phenothiazines such as prochlorperazine (Compazine) are the best studied and most widely used standard antiemetic agents.¹ Although phenothiazines have generally had greater antiemetic activity than placebo in controlled studies,^{2 3 4} this activity is only of marginal benefit to most patients.¹ Because emesis is poorly controlled by standard drugs, recent trials have included newer agents, such as the cannabinoids delta-9-tetrahydrocannabinol and nabilone. Several studies have shown that these investigational agents are effective as antiemetics^{2 , 5 6 7 8}; however, the side effects of ataxia, sedation, and dysphoria have. . .