Phase Ia/Ib chemo-radiation trial of gemcitabine and dose-escalated thoracic radiation in patients with stage III A/B non-small cell lung cancer

Introduction: The safety of dose-escalated thoracic radiation concurrent with gemcitabine in patients with inoperable stage III non-small cell lung cancer has not been studied. Patients and Materials: The maximal tolerated dose of 35 mg/m(2) twice-weekly gemcitabine and concurrent standard thoracic radiation was established in a previous phase la trial. In this study, a second patient cohort (phase Ib) received twice-weekly gemcitabine concurrent with three-dimensional dose-escalated thoracic radiation (60-74 Gy) after two cycles of induction chemotherapy: gemcitabine (1000 mg/m(2)) day 1 and 8 and carboplatin (area under the curve 5.0-5.5) day 1 every 21 days. Results: Twenty-three patients were entered in the phase Ib portion of this trial. Grade III/IV hematologic toxicity was primarily thrombocytopenia (22%) and neutropenia (26%). Grade III/IV esophageal toxicities occurred in 17% of patients, and grade III radiation pneumonitis/dyspnea was observed in 7 of 23 patients. The median and 2-year survival for phase Ib patients were 17.4 months and 32%, respectively. The overall 1- and 2-year survival for all 39 patients (16 phase la, 23 phase Ib) was 69% and 32%, respectively. Conclusions: Combining 74-Gy thoracic radiation and concurrent gemcitabine is feasible, but the use of this regimen should be limited to the confines of a clinical trial. A randomized phase 11 trial through the Cancer and Leukemia Group B is underway to further evaluate the efficacy of this regimen.