Phase I study of cisplatin analogue nedaplatin, paclitaxel, and thoracic radiotherapy for unresectable stage III non-small cell lung cancer

The standard treatment of unresectable stage III non-small cell lung cancer is concurrent chemoradiotherapy in patients in good general condition, but where the optimal chemotherapeutic regimen has not been determined. Patients with unresectable stage III non-small cell lung cancer received nedaplatin (80 mg/m2) and paclitaxel on day 1 every 4 weeks for 3-4 cycles and concurrent thoracic radiotherapy (60 Gy/30 fractions for 6 weeks) starting on day 1. The dose of paclitaxel was escalated from 120 mg/m2 in level 1, 135 mg/m2 in level 2 to 150 mg/m2 in level 3. A total of 18 patients (14 males and 4 females, with a median age of 62.5 years) were evaluated in this study. Full cycles of chemotherapy were administered in 83% of patients in level 1, and in 50% of patients in levels 2 and 3. No more than 50% of patients developed grade 4 neutropenia. Transient grade 3 esophagitis and infection were noted in one patient, and unacceptable pneumonitis was noted in three (17%) patients, two of whom died of the toxicity. Dose-limiting toxicity (DLT), evaluated in 15 patients, noted in one of the six patients in level 1, three of the six patients in level 2 and one of the three patients in level 3. One DLT at level 2 developed later as radiation pneumonitis. Thus, the maximum tolerated dose was determined to be level 1. The overall response rate (95% confidence interval) was 67% (41-87%) with 12 partial responses. The doses of paclitaxel and nedaplatin could not be escalated as a result of severe pulmonary toxicity. (author)