Efficacy of ondansetron tablets in the management of chemotherapy-induced emesis: review of clinical trials.

The selective 5-hydroxytryptamine3 antagonist ondansetron has been shown to be effective in preventing nausea and vomiting associated with highly emetogenic cisplatin chemotherapy. Two multicenter, placebo-controlled, dose-comparison studies (S3A-361 and S3A-362) were undertaken to investigate the efficacy and safety of oral ondansetron in patients receiving non-cisplatin, cyclophosphamide-based regimens in the outpatient setting. Chemotherapy-naive patients undergoing their first cycle of cyclophosphamide-based (> or = 500 mg/m2) chemotherapy were randomized to receive placebo or ondansetron, 1, 4, or 8 mg, three times per day for 3 days. In addition to cyclophosphamide, all patients received doxorubicin, methotrexate, or another low-to-moderately emetogenic agent. In study S3A-361, 318 of 349 patients were evaluable for efficacy; 297 of 324 patients in study S3A-362 were evaluable for efficacy. All patients in both studies were evaluable for safety. All ondansetron groups were superior to placebo groups in both studies for all measured efficacy parameters. In the two studies combined, 14%, 47%, 65%, and 66% of patients in the placebo, 1-, 4-, and 8-mg ondansetron groups, respectively, experienced no emetic episodes. The rate of therapeutic failure was statistically lower in the ondansetron groups in both studies compared with the placebo groups. In addition, therapeutic failure decreased in a dose-dependent manner. Severity of nausea, food intake, time to first emetic episode, and need for rescue antiemetics were also improved for the ondansetron groups. When the patients were stratified for doxorubicin-containing regimens, those patients receiving doxorubicin had a lower response rate with placebo and ondansetron than those on non-doxorubicin regimens. However, a dose-related improvement in efficacy was still observed with ondansetron in this subset of patients. In patients receiving the more emetogenic high-dose cyclophosphamide (> or = 600 mg/m2) regimens, a dose-related improvement in efficacy also was observed. In conclusion, oral ondansetron was found to be an effective and safe antiemetic for patients receiving cyclophosphamide-based chemotherapy in the outpatient setting. The 8-mg dose was optimal, particularly in patients receiving doxorubicin-containing or high-dose cyclophosphamide regimens.