Phase I study to determine the MTD of paclitaxel given three times per week during concurrent radiation therapy for stage III non-small cell lung cancer.

OBJECTIVE

To evaluate the toxicity and the maximum tolerated dose (MTD) of paclitaxel concurrently with three-dimensional (3D) conformal radiotherapy for patients with locally advanced non-small cell lung cancer (LANSCLC) after 2-3 cycles of induction chemotherapy.

RESEARCH DESIGN AND METHODS

Patients with histologically proven stage III non-small cell lung cancer (NSCLC) were eligible. Induction chemotherapy regimen included cisplatin (40 mg/m2) on days 1 and 2, and vinorelbine (25 mg/m2) on days 1 and 8 every 3 weeks for 2 or 3 cycles, followed a month later by continual three-dimensional (3D) conformal radiotherapy (60 Gy in 30 fractions for 6 weeks) delivered concurrently with paclitaxel dose escalating from the lowest level, 15 mg/m2, twice weekly, 6 weeks in all, to the highest level, 15 mg/m2, three times a week, 6 weeks in all.

MAIN OUTCOME MEASURES

The MTD was defined as the highest safely tolerated dose at which no more than one patient out of six experiences dose-limiting toxicity, with the next higher dose having at least two out of six patients experience dose-limiting toxicity (DLT).

RESULTS

Twenty-three patients were enrolled in this study. The maximum tolerated dose of paclitaxel during 3D-conformal radiotherapy was not reached at 15 mg/m2, three times a week, 6 weeks in all, a level which has been recommended for Caucasian patients with LANSCLC without induction chemotherapy. The overall response rate of induction chemotherapy alone was 47.8% (0% complete remission, 47.8% partial remission, 39.1% stable disease, 13% progressive disease) and that of induction chemotherapy plus concurrent treatment was 78.3% (18/23), including 8.7% (2/23) complete remissions. None of the patients died as a result of toxicity. The median survival time was 23.0 months.

CONCLUSIONS

15 mg/m2 of paclitaxel, three times a week, concurrently with 3D-conformal radiotherapy for patients with locally advanced NSCLC after 2 or 3 cycles of induction chemotherapy is a safe and effective dose, according to our preliminary study.