[Study of the clinical pharmacokinetics of fotemustine in various tumor indications]

Fotemustine (S 10036) is a new nitrosourea compound whose antitumoral activity has been demonstrated, particularly in disseminated malignant melanoma. Pharmacokinetic parameters of this drug were investigated during phase II clinical trials and compared according to tumor type. Twenty-six patients entered the study and received an induction treatment (weekly 100 mg/sq.m of fotemustine in 250 ml of 5% glucose in water over a one-hour IV infusion for 3 consecutive weeks) followed by a 4-week rest period. A maintenance therapy (100 mg/sq.m every three weeks) was proposed in stabilized or responsive patients. Plasmatic assay of fotemustine was carried out by HPLC. Seventy-one cycles were analyzed. A short half-life and a large intra and inter-individual variability of all kinetic parameters (especially plasmatic clearance) was found independent of tumour type. The study of patient's clinical behaviour was shown to be related to the clearance value obtained during the first treatment cycle which seems to predict the clinical response in the case of malignant melanoma. This finding needs to be confirmed in a larger number of patients and in other tumor localizations.