Clinical assessment of ramosetron HCl oral preparation in the treatment of nausea and vomiting induced by cisplatin: A multicenter, randomized, parallel-design, double-blind comparative study with ondansetron HCl

Background: Nausea and vomiting induced by anticancer drugs cause considerable stress to patients and complicate drug administration and/or cause patients to refuse further courses of therapy. Oral antiemetics, such as ondansetron HCl, were developed to provide a wider selection of drugs to treat chemotherapy-induced nausea and vomiting. Ramosetron HCl oral preparation (intraoral disintegrator) was specially formulated to be taken without water. Studies have shown that ramosetron oral preparation has potent inhibitory effects on cisplatin-induced vomiting. Objective: This multicenter, randomized, parallel-design, double-blind comparative study examined the efficacy, tolerability, and usefulness of ramosetron oral preparation compared with ondansetron HCl oral preparation in inhibiting nausea/vomiting (including retching) induced by the anticancer drug cisplatin. Methods: Japanese inpatients aged greater than or equal to20 years with cancer were eligible. Patients received either a single IV administration or less than or equal to4-hour IV infusion of cisplatin greater than or equal to50 mg/m(2) (including concomitant use with other anticancer drugs) at 30 participating centers in Japan. All patients were randomized to receive 1 tablet each of ramosetron 0.1 mg and ondansetron placebo or ondansetron HCl 4 mg and ramosetron placebo simultaneously 1 hour before administration of cisplatin therapy. Patients were observed for 24 hours from the start of cisplatin infusion. The severity of nausea was assessed and the number of vomiting episodes was recorded for each patient. The causal relationships between all adverse events and study drugs were assessed. Results: This study was performed in 151 patients hospitalized at 30 institutions. The ramosetron group (group R) included 75 patients; the ondansetron group (group O), 76. Of these, 150 (75 in each group) were included in the analysis of tolerability, and 136 (67 and 69 patients in groups R and O, respectively; 75 women, 61 men) were included in the analysis of clinical efficacy/usefulness. In the latter analysis, the percentages of patients exhibiting less than or equal to2 vomiting episodes 0 to 24 hours after cisplatin infusion were 74.6% (50/67) in group R and 63.8% (44/69) in group O. The percentages of patients displaying mild nausea or none 0 to 24 hours after infusion were 68.7% (46/67) and 63.8% (44/69), respectively. Although no significant differences in the incidences of nausea and vomiting were observed between the 2 groups, both effects were slightly more prevalent in group R than group O. Drug-related adverse events included mild or moderate dull headache (2 patients in group R), moderate painful headache (1 in group O), and moderate fever (1 in group R). Conclusions: Both ramosetron 0.1 mg and ondansetron 4 mg oral preparations showed satisfactory antiemetic effects when given 1 hour before cisplatin therapy and were judged clinically useful in this group of patients.