[Gastrointestinal toxicity induced by anticancer drugs--including new antiemetic drugs]

In a cross-over design of a study of prevention of emesis induced by cancer chemotherapy done in Saitama Cancer Center, the efficacy of oral lorazepam was superior to that of i.v. domperidone. And then, we proceeded a parallel study with use of oral lorazepam and oral domperidone. However, in this situation lorazepam was not superior to domperidone despite accrual of more than 60 patients. Recently, a multi-institutional study has been started in October of 1988 in an evaluation of the efficacy and safety of the new anti-emetic drug of a 5HT3 receptor antagonist, ondansetron. Two methods of its administration were designed. In one study ondansetron was given 2 hr prior to non-platinum chemotherapy as an 2 or 8 mg dose by oral administration, followed by receiving it 6 hr and 12 hr after chemotherapy. In another study, it was given 15 min prior to cisplatin including chemotherapy as an 2 or 8 mg loading dose by i.v. injection over 5 min, followed by continuous infusion at a rate of 0.25 mg/h or 1 mg/h for 24 h, respectively. Efficacy was assessed by measurement of the number of episodes of retching and vomiting occurring in the 24h after administration of chemotherapy and by an assessment of nausea during the same period. This time the major efficacy category was adopted, which is made up of the complete responder and major responder categories of both vomiting and nausea. 19 patients were evaluable for efficacy in the non-platinum group; the major efficacy rates showed 45% in 2 mg-given group and 88% in 8 mg-given group, respectively. 108 patients were evaluable for efficacy in the cisplatin group: the major efficacy rates showed more than 70% in both 2 mg and 8 mg-given group. However, in the patients given more than 75 mg/mg2 of cisplatin, the major efficacy rates were 55% in the 2 mg-given group, compared to 73% in the 8 mg-given group. Ondansetron was well tolerated, with no significant drug-related adverse events.