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.