EFFICACY OF ORAL ONDANSETRON, A SELECTIVE ANTAGONIST OF 5-HT3 RECEPTORS IN THE TREATMENT OF NAUSEA AND VOMITING ASSOCIATED WITH CYCLOPHOSPHAMIDE-BASED CHEMOTHERAPIES

We evaluated the efficacy and safety of oral ondansetron, a selective antagonist of 5-HT3 receptors, for the treatment of nausea and vomitin g associated with cyclophosphamide-based chemotherapy (>500 mg/m2). In this trial 324 chemotherapy-naive cancer patients, mostly females wit h breast cancer, were randomized to receive either placebo or ondanset ron 1 mg, 4 mg, or 8 mg three times per day for 3 days. There were no differences in the doses of cyclophosphamide, doxorubicin, and methotr exate between the study groups. All ondansetron dose groups were super ior to the placebo control group (p < .001) for all measured efficacy parameters (complete response, number of emetic episodes, therapeutic failures, need of rescue antiemetics). No emetic episodes were reporte d by 9 (12%), 29 (37%), 48 (64%), and 47 (66%) of the placebo patients and the 1-mg, 4-mg, and 8-mg dose of ondansetron patients, respective ly. Nausea was reduced and food intake was improved for all the ondans etron groups. A more severe emetic response was observed in patients r eceiving cyclophosphamide and doxorubicin combination chemotherapy. In this subgroup of patients, 66%, 38%, 25%, and 16% of the placebo grou p and 1-mg, 4-mg, and 8-mg ondansetron patients, respectively, require d rescue antiemetics. No significant toxic effects were observed in th is study. A higher incidence of headaches and gastrointestinal complai nts (constipation, abdominal pain) were observed in the three ondanset ron groups. In conclusion, oral ondansetron is an effective and well-t olerated antiemetic treatment in the management of cancer patients rec eiving ambulatory cyclophosphamide-based chemotherapy. These results s upport the view that serotonin and 5-HT3 receptors play an important r ole in cyclophosphamide-induced nausea and vomiting.