Randomized, Double-blind, Placebo-controlled Trial on Preventive Effect of Cloxazolam against Cisplatin-induced Nausea and Vomiting

We conducted a randomized,double-blind,placebo-controlled trial to investigate the preventive effect of the administration of the anxiolytic agent cloxazolam (3 mg/day) together with standard antiemetic measures (5-HT3 receptor antagonist and dexamethasone) for nausea and vomiting in lung cancer patients undergoing chemotherapy with cisplatin (>60 mg/m2).Subjects were randomly assigned to a cloxazolam group and placebo group by the minimization method,and the preventive effects in each group were compared over 5 days of administration starting on the night before chemotherapy.The allocation conditions were psychological state of patients digitized using a self-rating depression scale,concurrent medications,presence or absence of nausea and vomiting before treatment,and sex.The severity of nausea was scored on a self-rating survey form for 7 days beginning on the day that chemotherapy was started,and the overall clinical effect was assessed on the basis of this score and the number of times patients vomited.Data were recorded for 38 subjects.Nausea and vomiting were significantly inhibited in the cloxazolam group from Day 1 to Day 3 of administration.The cumulative total inhibition rate for nausea and vomiting during the protocol period was also significantly better in the cloxazolam group than in the placebo group.A stratified analysis of the relationship between the patient's psychological state and the antiemetic effect showed that the inhibitory effect of cloxazolam with respect to delayed nausea was significantly higher when the level of depression was low immediately before chemotherapy and when there had been a vomiting event during previous chemotherapy.