Diaminodichloroplatinum: a phase I study showing responses in testicular and other tumors.
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Biomedical subjects
Publications and source records attributed to D J Higby.
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An unusual donor reaction characterized primarily by lower abdominal and/or perineal pain occurs in 1.2 per cent of donors during filtration leukapheresis (FL). The reaction occurs almost exclusively in female donors. Corticosteroid pretreatment appears to be highly effective in preventing the reaction. The pathogenesis of this donor problem is speculative.
Currently, the frequency of granulocyte donation is limited by the prolonged circulation of hydroxyethyl starch (HES). We conducted a Phase I, uncontrolled, multicenter trial to evaluate both the efficacy and safety of a rapidly excreted low-molecular-weight analog of HES (LMW-HES). Seventy-five donors underwent 179 centrifugation leukapheresis procedures using LMW-HES as the red-cell-sedimenting agent. The efficacy of LMW-HES was established by harvesting adequate numbers of leukocytes. Most granulocyte concentrates contained at least 20 X 10(9) neutrophils when 8 l of blood was processed from donors optimally stimulated with steroids. The safety of LMW-HES was documented by the detection of almost no clinically significant adverse effects. In only 1.7 percent of procedures did donors require special attention, and only 1 of 179 procedures (0.6%) was permanently discontinued. Results of laboratory studies were usually normal or their values decreased transiently (approximately 15-25%) as a consequence of plasma volume expansion (dilution). Based on previous experience with HES, LMW-HES and HES perform comparably during leukapheresis. When commercially available, use of this new, rapidly excreted analog should permit more frequent leukapheresis donation.
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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.
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