Two-cycle cisplatin kinetics in patients with ovarian and mammary cancer

The kinetics of platinum (Pt) in patients treated for two-cycle therapy with cis-DDP for ovarian or mammary carcinoma were investigated. Cis-DDP, at a dose of 65 mg/m2, was administered i.v. over 60 min to 6 patients every 3 weeks. Plasma was collected before and 1, 2, 4, 8, 24, and 48 h after the start of the first and second infusions. The levels of Pt in the patients' plasma were determined by flameless atomic absorption spectroscopy. Plasma levels were analyzed by a two-compartment open pharmacokinetic model. Plasma decline was biphasic, both after the first and the second cycle. In all patients, the calculated t1/2 of the rapid phase increased after the second cycle (from a mean value of 0.39 h to 2.45 h), whereas the t1/2 of the slow phase increased about threefold in 3 subjects. In the latter, we observed an increase of AUC and a decrease of total body clearance.