Phase I and pharmacological study of paclitaxel given over 3 h with cisplatin for advanced non-small cell lung cancer

Background: To establish the toxicities and maximum tolerated dose of paclitaxel given over 3 h in combination with cisplatin, to determine the pharmacokinetic profiles of these two drugs and to observe their antitumor activity, we conducted a combination phase I study in non-small cell lung cancer. Methods: Patients received paclitaxel doses of 150-210 mg/m(2) given over 3 h and cisplatin doses of 60-80 mg/m(2) as a 1 h infusion 2 h after the end of the paclitaxel infusion. Results: A total of 25 patients with previously untreated non-small cell lung cancer were enrolled. Granulocytopenia was the most frequent hernatological toxicity and the most prominent non-hematological toxicity was sensory dominant neuropathy. Two of six patients experienced dose limiting toxicities (leukopenia, infection and neuropathy) at a dose of paclitaxel 210 mg/m2 and cisplatin 60 mg/m(2), which was considered the maximum tolerated dose. There were seven partial responses among 24 evaluable patients, for an overall response rate of 29%. The median survival time was 341 days and the 1 year survival rate was 45.8%. As the paclitaxel pharmacokinetic parameters in this study were consistent with those of our previous single agent study, we found no significant drug-drug interaction between the 3 h infusion paclitaxel and cisplatin. Conclusion: The recommended doses for further study are determined to be paclitaxel 180 mg/m(2) and cisplatin 80 mg/m(2). This is a well-tolerated and active regimen for non-small cell lung cancer. In view of the promising survival outcome, further evaluation in prospective randomized trials versus other regimens is warranted.