Pharmacokinetics of cisplatin in patients receiving interleukin-2-containing treatment regimens

Plasma cisplatin pharmacokinetics were determined in 6 patients enrolled in a phase I trial of combined high-dose cisplatin and Interleukin-2 (IL-2) therapy. Cisplatin (100 mg/m2) was given in 3% saline as a 3-h infusion on days 1 and 8 of each 28-day cycle; IL-2(2-4 x 10(6) units/m2) was given as an i.v. bolus on days 15-19 in a dose escalation trial. Peak total and ultrafiltrate plasma platinum concentrations were 1.15 and 0.172 micrograms/ml for cycle 1 and 1.2 and 0.124 micrograms/ml for cycle 3, respectively. The AUCs for total and ultrafiltrate plasma platinum were 7.33 and 0.965 micrograms/ml per hour for cycle 1 and 8.48 and 0.924 micrograms/ml per hour for cycle 3, respectively. Total body clearances for total and ultrafiltrate platinum were 0.051 and 0.525 ml/h for cycle 1 and 0.042 and 0.443 ml/h for cycle 3, respectively. These data demonstrate no significant effects of IL-2 on the plasma pharmacokinetics of cisplatin in the dose schedule given and support the feasibility of this combined modality therapy.