Multimodality treatment of unresectable stage III non-small cell lung cancer: Interim analysis of a phase II trial with preoperative gemcitabine and concurrent radiotherapy

Objective: We report the preliminary results of a phase II trial undertaken to determine the feasibility and efficacy of gemcitabine and concurrent radiotherapy in patients with inoperable stage III non-small cell lung cancer. Methods: Between February 2001 and June 2003, a total of 46 patients (37 male and 9 female, median age 64 years) with clinical stage III non-small cell lung cancer (41 cIIIA and 5 cIIIB) were enrolled in a combined chemoradiation protocol with gemcitabine as the chemotherapeutic agent. Gemcitabine (350 mg/m²) was administered weekly for 5 consecutive weeks as a 30-minute intravenous infusion before radiotherapy (total dose 50.4 Gy, 1.8 Gy/d). Toxicity was routinely assessed. Those patients with disease judged to be resectable at restaging underwent surgery. Results: Toxicity was moderate, with the exception of 1 grade 3 thrombocytopenia. All but 5 patients were available for restaging. No complete responses were observed. Thirty-four patients (82.9%) had partial responses, 5 (12.2%) had stable disease, and 2 (4.9%) had progressive disease. Twenty-nine of 46 patients (63%, 27 cIIIA and 2 cIIIB) underwent surgery. Radical resection was possible in all cases. Surgery included 17 lobectomies, 4 bilobectomies, and 8 pneumonectomies. There were no deaths. Morbidity was 13.8% (4/29). Pathologic downstaging to stage 0 or I was observed in 18 patients (39%, 18/46). After a median follow-up of 13 months (range 2-28 months), 24 of the patients who had undergone operation (86.2%) were alive, with a median disease-free survival of 16 months. Overall 2-year survival was 66.1%, with a significant difference between resected and unresected disease (82% vs 36%, P = .0002). Conclusion: The results of this induction trial confirm the feasibility and the efficacy of gemcitabine with concurrent radiotherapy.