Phase III double-blind comparison of intravenous ondansetron and metoclopramide as antiemetic therapy for patients receiving multiple-day cisplatin-based chemotherapy.

BACKGROUND. Ondansetron hydrochloride is a selective serotonin subtype 3 (5HT3) receptor antagonist that has been shown to be an effective antiemetic in patients receiving cisplatin chemotherapy. METHODS. This double-blind study compared the safety and efficacy of intravenous ondansetron with metoclopramide in patients receiving a 4- or 5-day regimen of cisplatin (20-40 mg/m2/day) combination chemotherapy. Forty-five patients were enrolled, and efficacy of the drug therapy could be studied for all 45. Patients were randomly assigned (1:1) to receive three daily intravenous doses of either 0.15 mg/kg ondansetron or 1 mg/kg metoclopramide. All patients were monitored daily for the number of emetic episodes (vomiting or retching), severity of nausea, adverse events, and laboratory safety parameters. RESULTS. Seven (30%) patients who received ondansetron had no emetic episodes throughout the entire study period compared with two (9%) who received metoclopramide (P = 0.077). The greatest difference in antiemetic efficacy was seen on day 1, when 18 (78%) patients who received ondansetron had no emetic episodes compared with 3 (14%) patients who received metoclopramide (P < 0.001). Significantly fewer antiemetic treatment failures (more than five emetic episodes or withdrawal from the study) occurred with patients given ondansetron (9%) than with those given metoclopramide (50%) during the entire study period (P = 0.002). The most commonly reported adverse event associated with ondansetron therapy was headache (controlled with acetaminophen), whereas diarrhea and restlessness were the most commonly reported adverse events associated with metoclopramide therapy. Extrapyramidal symptoms were judged to have occurred in 13 patients who received metoclopramide and 1 patient who received ondansetron. However, the patient who received ondansetron subsequently was judged to have had an anxiety attack. In patients with low or normal baseline transaminase values, a greater percentage who received ondansetron had transient increases as great as twice the upper limit of normal in aspartate transaminase (5% versus 0%) and alanine transaminase (17% versus 6%) than those who received metoclopramide. CONCLUSIONS. Ondansetron is superior to metoclopramide as antiemetic therapy for multiple-day cisplatin-based chemotherapy.