Phase II trial of neoadjuvant therapy with carboplatin, gemcitabine plus thalidomide for stages IIB and III non-small cell lung cancer

INTRODUCTION: This phase II study assessed the clinical activity of neoadjuvant therapy with carboplatin, gemcitabine, and thalidomide in patients with stage IIB to IIIA non-small cell lung cancer (NSCLC). A secondary goal was to assay a panel of candidate serum biomarkers before and after neoadjuvant therapy. METHODS: Patients received three 21-day cycles consisting of gemcitabine (1000 mg/m) on days 1 and 8, carboplatin (area under the curve, 5.5) on day 1, and thalidomide (200 mg) daily after a gradual dose escalation. RESULTS: A total of 22 patients (12 women, 10 men) were enrolled with inoperable stage IIB NSCLC (32%) or III NSCLC (68%). Median age was 53 years (range: 32-78). Sixty-six cycles of neoadjuvant therapy were administered with 10 cycles requiring dose reductions (21.28%). Response rates were 70% for partial response (n = 14), 20% for disease stability (n = 4), and 10% for disease progression (n = 2). Disease in 14 patients (70%) was downstaged, allowing for 10 lobectomies (45.5%), one bilobectomy (4.5%), and 3 pneumonectomies (13.64%). Grades 3/4 hematologic events included neutropenia (55%), thrombocytopenia (14%), and anemia (14%). Grade 3 skin toxicity was reported in one patient due to thalidomide. Posttreatment increases from baseline in serum levels of angiopoietin (100 pg/ml), platelet/endothelial cell adhesion molecule 1 (100 pg/ml), hepatocyte growth factor (100 pg/ml), vascular endothelial growth factor (10 pg/ml), and interleukin-8 (10 pg/ml) corresponded to a reduction in the probability of death (p = 0.09, 0.055, 0.097, 0.052, and 0.095, respectively). Overall survival was 3.6 years (95% CI: 1.938-∞). CONCLUSION: This neoadjuvant regimen was well tolerated and effective in inoperable NSCLC and warrants additional investigation.