COMPARISON OF THE 5-HYDROXYTRYPTAMINE3 (SEROTONIN) ANTAGONIST ONDANSETRON (GR-38032F) WITH HIGH-DOSE METOCLOPRAMIDE IN THE CONTROL OF CISPLATIN-INDUCED EMESIS

To compare ondansetron (GR 38032F), a 5-hydroxytryptamine3-receptor antagonist, with metoclopramide in the prophylaxis of acute cisplatin-induced emesis, we conducted a double-blind crossover study in 97 patients scheduled to receive cisplatin (80 to 100 mg per square meter of body-surface area) for treatment of cancer. None had received chemotherapy before this trial. Among the 76 patients who satisfactorily completed both parts of the study, complete or nearly complete control of emesis (i.e., no episodes of emesis occurred, or only one or two) was achieved in 57 of 76 treatments (75 percent) with ondansetron and in 32 of 76 treatments (42 percent) with metoclopramide (P<0.001). Ondansetron was also more effective in controlling acute nausea, as assessed with a visual-analogue scale (P = 0.019) or a graded scale (P = 0.024). There was a significant preference among patients for ondansetron (55 vs. 26 percent; P = 0.006). Dystonic reactions were observed during three treatments with metoclopramide; both agents were otherwise well tolerated. We conclude that ondansetron is more effective than metoclopramide in the control of cisplatin-induced nausea and vomiting, and that this suggests that serotonin is an important mediator of this side effect. ALL patients vomit during the 24 hours after the administration of high doses of cisplatin unless given antiemetic agents,1 and none of the currently available antiemetic regimens are entirely effective. Metoclopramide has been considered the most effective single agent, but nearly complete control of emesis (i.e., only one or two episodes) has been achieved in only 38 to 60 percent of patients given high doses by intermittent infusion.1 2 3 Its effectiveness may be enhanced by administering it in a loading dose followed by a continuous infusion.4 In some patients, however, high doses of metoclopramide cause distressing extrapyramidal reactions5 and sedation1 because… © 1990, Massachusetts Medical Society. All rights reserved.