Neoadjuvant chemotherapy with gemcitabine-containing regimens in patients with early-stage non-small cell lung cancer.

Background: Surgical resection alone remains suboptimal for patients with early-stage (I or II) non-small cell lung cancer. Two similar randomized phase II trials were conducted to define an active preoperative regimen in this disease state.

Methods: In the first study, patients were randomized to receive gemcitabine 1000 mg/m2 on days 1 and 8 plus cisplatin 80 mg/m2 on day 1 (GC) or gemcitabine 1000 mg/m2 on days 1 and 8 plus carboplatin area under the curve 5.5 on day 1 (GCb). In the second trial, patients received the same regimen of GCb or gemcitabine 1000 mg/m2 on days 1 and 8 plus paclitaxel 200 mg/m2 on day 1 (GP). Cycles were repeated every 21 days for three cycles. The primary end point was pathologic complete response (pCR) rate.

Results: Eighty-seven eligible patients were randomized (GC n = 12, GP n = 35, and GCb n = 40), and 71 (82%) underwent surgery after chemotherapy. The confirmed pCR rate was 2.3% (2 of 87, 95% confidence interval 0.3-8.1). Clinical response rate was 28.7%, complete resection rate was 91.5% (65 of 71 patients), and perioperative mortality rate was 2.8%. As of October 2006, median survival for all patients was 45 months (65.5% censored), with 87.2% alive at 1 year and 69.8% alive at 2 years.

Discussion: Neoadjuvant chemotherapy with gemcitabine was feasible and well tolerated, and outcomes were similar to other reports of this treatment strategy. However, no regimen achieved the predefined pCR rate that would be sufficient to warrant further evaluation in the phase III setting. This trial design provides an efficient way of providing a rationale for choosing or rejecting regimens of potential value.