A DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF IV DOLASETRON MESILATE INTHE PREVENTION OF RADIOTHERAPY-INDUCED NAUSEA AND VOMITING IN CANCER-PATIENTS

The aim of this work was to measure the safety and efficacy of single i.v. doses of dolasetron mesilate for the control of emesis caused by single high-dose (at least 6 Gy) radiotherapy to the upper abdomen. Th e double-blind, placebo-controlled, multicenter study stratified patie nts on the basis of being naive or nonnaive to radiotherapy. Patients with or without a history of previous chemotherapy were enrolled. Pati ents were randomized to receive placebo or 0.3, 0.6, or 1.2 mg/kg dola setron mesilate 30 min before radiotherapy, then monitored for 24 h. A ntiemet ic efficacy was assessed from the time to the first emetic epi sode or rescue: from whether there was a complete response (0 emetic e pisodes/no rescue medication) or a complete-plus-major response (0-2 e metic episodes/no rescue medication), from the severity of nausea (rat ed by patients and the investigator), and from the investigator's asse ssment of efficacy, Fifty patients completed the study (owing to chang ing medical practice, enrollment objectives were not met; consequently , no significant linear dose trend was expected). Pooled dolasetron wa s superior to the placebo in its effect on the time to first emesis or rescue in radiotherapy-nonnaive patients (P=0.015). Dolasetron was st atistically superior to the placebo in the overall population on the b asis of a complete plus major response: 54%, 100%, 93%, and 83% for th e placebo and 0.3-, 0.6-, and 1.2-mg/kg doses respectively (P=0.002). The low response in the highest dose group may be due to an imbalance in the number of chemotherapy-nonnaive patients in that group. Dolaset ron was superior to the placebo on the basis of nausea assessed by the investigator (P=0.024) and administration of rescue medication (P=0.0 06), Complete response at the 0.3-mg/kg dose was superior to results w ith the placebo (P=0.050), Treatment-related adverse events were rare, mild to moderate in intensity, and evenly distributed across the four groups, Overall, dolasetron mesilate was effective and well-tolerated in the control of single, high-dose radiotherapy-induced emesis.