Phase I clinical evaluation of cytarabine and cisplatin in patients with advanced cancer.

Studies in cell culture systems and tumor-bearing animals have demonstrated synergistic cytotoxicity of cytarabine (ara-C) and cisplatin. We have conducted a phase I trial to assess the toxic effects and tolerable doses of these drugs in patients with advanced cancer. Forty-five such patients were treated with varying dosages of ara-C infused continuously during Days 1-3 of a 28-day cycle. Cisplatin at a dose of 100 mg/m2 was administered on Day 2 of the cycle. Using this schedule, the maximally tolerated dose of ara-C in previously untreated patients was 60 mg/m2/day (180 mg/m2). Hematologic toxicity was dose-limiting with median wbc and granulocyte count nadirs of 1800 and 168/mm3, respectively. Reduction of the cisplatin dose while maintaining the ara-C dose at 60 mg/m2/day resulted in less myelosuppression, suggesting that these drugs may have synergistic effects on the bone marrow. Objective responses were seen in six of 41 evaluable patients, including five of 12 patients with non-small cell lung cancer. The severe bone marrow toxicity observed at relatively low drug doses and the 42% response rate in patients with non-small cell lung cancer suggest that the combination of ara-C and cisplatin has substantial clinical activity. Phase II trials are warranted in non-small cell lung cancer and other tumors.