Early clinical trial of MDL 73.147 EF: a new 5-HT3-receptors antagonist for the prevention of chemotherapy-induced nausea and vomiting

Abstract

Background: Like MDL 72.222, one of the first selective 5-hydroxytryptamine3 (5-HT3) receptors antagonist discovered, MDL 73.147 EF has been shown to possess antiemetic properties in the ferret model. We conducted a phase I study with MDL 73.147 EF in 31 patients, treated with emetogenic drugs over one to five days (cisplatin, cyclophosphamide, doxorubicin, dacarbazine).

Patients and methods: 5 groups of at least 5 patients received rising unit doses of MDL 73.147 EF (10 to 50 mg) intravenously before chemotherapy, with two more doses per day if needed. Nausea was assessed by a patient-completed visual analogue scale and episodes of vomiting recorded by an independent observer.

Results: 51.6% of the patients were complete responders on day one and 40% on days two to five. One patient was given other rescue antiemetic therapy. Adverse events included constipation (25.8%), mildly elevated blood pressure (12.9%) and other minor events. No extrapyramidal effects have been reported. There was no suggestion of dose-dependent efficacy at the dose levels studied in this limited set of patients.

Conclusions: We conclude that MDL 73.147 EF is a well tolerated and possibly effective antiemetic.