Phase I study of continuous-infusion cisplatin

Cisplatin was administered to 21 patients as a continuous infusion over 5 days. Doses of 20, 25, and 30 mg/m2/day were studied. When administered in 3 L of normal saline/day, continuous-infusion cisplatin at a dose of 30 mg/m2/day was associated with neuropathy in two of nine patients and creatinine elevations (greater than 2 mg/dl) in four. No neurotoxicity or nephrotoxicity was observed at lower doses. Severe thrombocytopenia (less than 50,000/microliter) was unrelated to dose and occurred in 19% of the courses. Leukopenia was minimal. Nausea and vomiting were easily controlled. No toxicity was seen in 38% of the courses. Nineteen patients were evaluable for response. Six patients achieved partial response (32%), five had minimal response (25%), and eight had progressive disease (42%) in this group. Seven patients had received cisplatin previously as a bolus treatment (20 mg/m2/day for 5 days) and failed on chemotherapy. Among these patients there was one with partial response, three with minimal response, and three with progressive disease. It is concluded that continuous-infusion cisplatin, as given in this protocol, is well-tolerated at a dose of 25 mg/m2/day and can result in responses in patients failing bolus cisplatin at high doses.