A phase I study of gemcitabine plus palliative radiation therapy for advanced lung cancer

Purpose: To determine the maximum-tolerated dose (MTD) and antitumor activity of twice-weekly gemcitabine when combined with palliative-dose thoracic radiation therapy (RT) in patients with recurrent or progressive lung cancer. Methods: Patients were enrolled in a dose-escalating study of gemcitabine with a starting dose level of 40 mg/m² given as 30-minute infusions twice weekly concurrent with RT. The RT dose was 30 Gy in 10 fractions, 5 fractions per week. Results: A total of 18 patients were enrolled on three dose levels: 40, 50, and 65 mg/m². Four patients came off study early due to rapid progression of disease and therefore were not evaluated. The MTD of gemcitabine was found to be 50 mg/m². Dose-limiting toxicities were grade-4 esophagitis in one patient and grade-4 neutropenia in another patient. Overall response included 1 partial response (PR). Local response included six PR, four minor response (MR), three stable disease (SD), and one progressive disease (PD). Conclusion: The MTD of gemcitabine with concominant palliative thoracic radiation therapy is 50 mg/m² twice weekly. The DLTs observed were grade-4 esophagitis and grade-4 myelotoxicity at 65 mg/m².