A phase I study of gemcitabine with concurrent radiotherapy in stage III, locally advanced non-small cell lung cancer

Purpose: Our goal was to find the maximum tolerated dose of gemcitabine administered concurrently with thoracic radiotherapy in locally advanced non-small cell lung cancer (NSCLC). Patients and Methods: Patients with stage III NSCLC and a radiation planning volume less than 2000 cm(3) were included. Treatment consisted of 6 weeks of thoracic radiation, 2 Gy daily for 5 days a week for a total dose of 60 Gy. Planning with multiple field arrangements and three-dimensional conformal technique was used. Patients were treated with gemcitabine, starting with a dose of 300 mg/m(2) in the 1st week of radiation. In subsequent cohorts, the weekly dosing frequency of gemcitabine was increased until weekly administration was reached. Thereafter, the doses of weekly gemcitabine were increased. Toxicity was measured using Common Toxicity of the National Cancer Institute (CTC), acute Radiation Therapy Oncology Group (RTOG), and late RTOG/European Organization for Research and Treatment of Cancer (EORTC) rating scales. Results: Twenty-seven patients were included, of whom 14 had stage IIIa. and 13 had stage IlIb. Dose-limiting toxicity was grade 3 esophagitis and grade 3 radiation pneumonitis in the patient cohort receiving gemcitabine 450 mg/m(2) once weekly. The mean actual treated radiation volume was 760 cm(3) (range, 289-1718 cm(3)). Conclusions: The maximum tolerated dose and frequency of gemcitabine in locally advanced NSCLC is 300 mg/m(2) once weekly during 6 weeks of thoracic radiotherapy, as long as the treatment volume does not exceed 2000 cm(3)