Phase I study of high-dose cis-dichlorodiammineplatinum(II) with forced diuresis.

Twenty-six patients including 11 with metastatic melanoma received cis-dichlorodiammineplatinum(II) at a dose of either 1 mg/kg or 60 mg/m2 given with intensive diuresis over a 6-hour period. This dose was administered twice weekly for the first three to eight courses and then at q3wk intervals. Eighteen patients received the dose schedule of 1 mg/kg and six patients received 60 mg/m2. A complete response was seen in one of four testicular tumors lasting for 6 months; partial responses were seen in three of 11 metastatic melanomas for 1, 1, and 2 months respectively, one of two osteogenic sarcomas for 4 months, one of one multiple myeloma for 2 months, and one of four testicular tumors for 1 month. A transient drop in creatinine clearance to 50%-75% of the baseline level was observed in 21% of the patients. Cytotoxic effects of cis-dichlorodiammineplatinum(II) are probably enhanced by this dose schedule as indicated by the consistent, moderate hematologic toxicity. Renal toxicity is ameliorated.