OBJECTIVE To compare the efficacy and safety of oral granisetron hydrochloride tablets with that of oral prochlorperazine sustained-release capsules in preventing nausea and emesis induced by moderately emetogenic chemotherapeutic agents. METHODS In this multicenter, double-blind, randomized, parallel group study, oral granisetron and oral prochlorperazine were compared in 230 chemotherapy-naive, adult cancer patients who received moderately emetogenic chemotherapy. Patients were stratified by gender and randomized to receive either 1.0 mg oral granisetron HCI twice a day for 7 days, or 10 mg oral prochlorperazine sustained-release capsules twice a day for 7 days. The first dose was given 1 hour before initiation of chemotherapy and the second dose 12 hours after the first dose. Patients were evaluated for emetic episodes, extent of nausea, and adverse events for 7 days after the start of chemotherapy. Primary efficacy parameters were complete response (no emetic episodes, no greater than mild nausea, no antiemetic rescue) and total control (no emetic episodes, no nausea, no antiemetic rescue) in the 24 hours after the start of chemotherapy. RESULTS Granisetron was significantly more effective than prochlorperazine in achieving a complete response (74% vs. 41%, respectively) and total control of nausea and vomiting (58% vs. 33%, respectively) at the 24-hour assessment. Complete response at 24 hours was significantly higher in the granisetron-treated patients than in prochlorperazine-treated patients. In women, granisetron showed a complete response rate of 69% versus 38% with prochlorperazine; in men, granisetron showed a complete response rate of 92% versus 61% with prochlorperazine. Both regimens were well tolerated, with headache (36% for granisetron, 29% for prochlorperazine) and constipation (31% for granisetron, 6% for prochlorperazine) the most common adverse events. CONCLUSIONS : Oral granisetron 1 mg twice a day was significantly more effective than oral prochlorperazine sustained release capsules 10 mg twice a day in complete response and total control of nausea and vomiting at 24 hours after chemotherapy. Both agents were well tolerated.