ACUTE ANTIEMETIC EFFICACY AND SAFETY OF DOLASETRON MESYLATE, A 5-HT3 ANTAGONISTS, IN CANCER-PATIENTS TREATED WITH CISPLATIN

Dolasetron mesylate (MDL 73,147EF), a new serotonin receptor (5-HT3) a ntagonist was administered to 164 cancer patients naive or nonnaive to chemotherapy, in single, rising doses of 10, 20, 30, 40, or 50 mg IV 15 minutes prior to an infusion of cisplatin. The severity of nausea a nd number of episodes of emesis were recorded during the 24-hour perio d following cisplatin administration. There were significant differenc es between the dose groups, sex, and naive and non-naive patients. The re were also significant dolasetron dose-dependent differences for no emesis (p = .01), less than 3 emetic episodes (p = .01), time-to-onset of nausea (p = .04), and time-to-onset of emesis (p = .003). The seve rity of symptoms was greater for females, for patients with previous c hemotherapy, and with shorter duration of cisplatin infusion. Adjustme nt for these variables and the study center reduced the associations b etween the dose of dolasetron mesylate and the outcome variables. The principal adverse events were headache (11%) and diarrhea (6%). Dolase tron mesylate was well tolerated; a single dose of 40 or 50 mg control led acute nausea and vomiting induced by highly emetogenic chemotherap y in the majority, in particular in chemotherapy-naive and male patien ts. In conclusion, 50 mg and a larger dose merit study in controlled t rials with stratification for sex and previous chemotherapy.