Gemcitabine-based combinations as preoperative therapy in resectable non-small-cell lung cancer

Surgical resection remains the standard of care in early-stage non-small-cell lung cancer (NSCLC). In those patients undergoing complete surgical resection, the dominant recurrence pattern is systemic with only a minority of patients experiencing local recurrence. Unfortunately, adjuvant chemotherapy (with or without thoracic radiation therapy) has not been proven to enhance survival in resected NSCLC. Preoperative or induction therapy offers several advantages over postoperative therapy, including earlier attention to systemic micrometastatic disease and enhanced tolerance to treatment. The feasibility of this approach has been demonstrated in several phase II as well as phase III trials predominantly in stage III NSCLC but also in stage IB and II NSCLC. In proof-of-concept phase III trials, the impact preoperative therapy has on survival has not been consistent, but most trials are small in patient number, limiting the power they have in detecting small but clinically meaningful differences. Gemcitabine-containing regimens have been evaluated in several phase II trials in resectable stage III NSCLC. The overall response rate has ranged from 53%-70% with the majority of patients undergoing complete surgical resection. Toxicity has been acceptable, and the combination of cisplatin/gemcitabine is currently being evaluated as induction therapy in several phase III trials. Ongoing trials in stage I-II NSCLC are incorporating gemcitabine-containing regimens in the preoperative setting. Continued evaluation of gemcitabine-containing regimens as preoperative therapy is warranted given their level of activity and tolerability in advanced NSCLC.