Weekly paclitaxel and nedaplatin with concurrent radiotherapy for locally advanced non-small-cell lung cancer: A phase I/II study

Objective: The purpose of this study was to determine the safety and efficacy of nedaplatin and paclitaxel when given concurrently with radiation therapy (RT) for locally advanced non-small-cell lung cancer (NSCLC). Methods: Nedaplatin was administered at a fixed dose of 20 mg/m(2), and paclitaxel was administered at a starting dose of 30 mg/m(2) with an incremental increase of 5 mg/m(2) until dose-limiting toxicity (DLT) occurred in more than one-third of the patients. The chemotherapy was administered once a week for 6 weeks. The FIT was given at a single daily dose of 2 Gy for 5 days per week. The pharmacokinetics of nedaplatin and paclitaxel were investigated. Results: Overall, 20 patients were recruited and assigned to three different treatment groups: group 1 (paclitaxel 30 mg/m(2)), group 2 (paclitaxel 35 mg/m(2)) and group 3 (paclitaxel 40 mg/m(2)). Pulmonary toxicity was the main toxicity which occurred in 16 of 20 patients. In group 3, grades 3 and 4 pulmonary toxicity occurred in two of six patients and grade 3 esophagitis in one patient. The maximum tolerated dose of paclitaxel in this study was 40 mg/m(2) and the recommended dose of paclitaxel was therefore 35 mg/m(2). Four complete and 11 partial responses were observed, resulting in a 75% overall response rate. The area under the concentration-time curve of paclitaxel in group 3 was significantly higher than that in group 1. Conclusion: Nedaplatin 20 mg/m(2) and paclitaxel 35 mg/m(2) could be safely administered for NSCLC with concurrent thoracic RT, and this regimen was effective. The most important DLT was pulmonary toxicity.