PLATINUM ACCUMULATION IN ADULT CANCER-PATIENTS RECEIVING CISPLATIN - PLASMA AND URINARY PLATINUM CONCENTRATIONS ON FIRST DRUG EXPOSURE

Total plasma platinum (TP) was measured over 21 days in 22 patients receiving a 6-hour intravenous infusion of the anticancer drug cisplatin 80 to 100 mg/m(2). Cisplatin was administered as a single agent to 3 ovarian cancer patients, in combination with fluorouracil to 12 head and neck cancer patients, and with bleomycin and etoposide to 7 patients with teratoma of the testis. The mean (+/- SD) peak TP was 2.59 +/- 0.35 mg/L at the end of the infusion. Postinfusion TP declined triphasically, with a mean (+/- SD) half-life, plasma clearance, apparent volume of distribution at steady-state and mean residence time (MRT) of 11.7 +/- 2.3 days, 2.4 +/- 0.88 ml/min/m(2), 49 +/- 13 L/m(2) and 15 +/- 3.5 days, respectively. At 21 days all patients had measurable TP (0.32 +/- 0.11 mg/L), with 13 to 40% of the area under the concentration vs time curve from zero to infinity (AUC(0-infinity)) remaining. 60% of the platinum dose remained to be excreted in urine, 4 days postinfusion, and the extrapolated mean MRT was 17.4 days. We conclude that a long TP terminal half-life is present in all patients, which will lead to platinum accumulation on consecutive cisplatin infusions at dose intervals of 3 weeks or less.