A phase III randomized trial of gemcitabine-oxaliplatin versus carboplatin-paclitaxel as first-line therapy in patients with advanced non-small cell lung cancer.

PURPOSE: This phase III study compared the efficacy and tolerability of gemcitabine and oxaliplatin (GEMOX) with paclitaxel and carboplatin (PCb) in chemotherapy-naive patients with stage IIIB/IV non-small cell lung cancer. PATIENTS AND METHODS: Patients aged 18 years or older were randomized to PCb (paclitaxel 225 mg/m followed by carboplatin area under the curve = 6 on day 1 every 3 weeks) or GEMOX (gemcitabine 1,000 mg/m on days 1 and 8 followed by oxaliplatin 130 mg/m on day 1 every 3 weeks) for up to six cycles. The primary end point was progression-free survival (PFS), with tumor response rate, overall survival (OS), and quality of life as secondary end points. RESULTS: : The study was terminated after 383 patients had been randomized (371 received treatment) as the incidence of adverse events had exceeded the protocol-specified safety threshold (≥ 20% in either arm). No formal statistical comparisons were conducted. Median PFS was 4.44 months and 4.67 months in the GEMOX and PCb groups, respectively. Objective response rates (complete or partial) were 15.2% and 22.4% in the GEMOX and PCb arms, respectively. Median OS was 9.90 months (GEMOX) and 9.24 months (PCb); post hoc analyses showed median OS in patients aged 70 years or older to be similar to those younger than 70 years. PFS was similar in both groups of patients with adenocarcinoma histology, although OS favored the GEMOX group. Quality of life was improved from baseline in both groups. Toxicity profiles were comparable between the groups. CONCLUSION: PFS, OS, and objective response rates with GEMOX were similar to PCb. Nevertheless, toxicities limit the adoption of this regimen for routine use in advanced non-small cell lung cancer.

Randomized, phase II trial of pemetrexed and carboplatin with or without enzastaurin versus docetaxel and carboplatin as first-line treatment of patients with stage IIIB/IV non-small cell lung cancer.

INTRODUCTION: Enzastaurin is an oral serine/threonine kinase inhibitor that targets protein kinase C-beta (PKC-ß) and the phosphatidylinositol-3-kinase/AKT pathway. This trial assessed pemetrexed-carboplatin ± enzastaurin to docetaxel-carboplatin in advanced non-small cell lung cancer. METHODS: Patients with stage IIIB (with pleural effusion) or IV non-small cell lung cancer and performance status 0 or 1 were randomized to one of the three arms: (A) pemetrexed 500 mg/m and carboplatin area under the curve 6 once every 3 weeks for up to 6 cycles with a loading dose of enzastaurin 1125 or 1200 mg followed by 500 mg daily until disease progression, (B) the same regimen of pemetrexed-carboplatin without enzastaurin, or (C) docetaxel 75 mg/m and carboplatin area under the curve 6 once every 3 weeks for up to six cycles. The primary end point was time to disease progression (TTP). RESULTS: Between March 2006 and May 2008, 218 patients were randomized. Median TTP was 4.6 months for pemetrexed-carboplatin-enzastaurin, 6.0 months for pemetrexed-carboplatin, and 4.1 months for docetaxel-carboplatin (differences not significant). Median survival was 7.2 months for pemetrexed-carboplatin-enzastaurin, 12.7 months for pemetrexed-carboplatin, and 9.2 months for docetaxel-carboplatin (log-rank p = 0.05). Compared with the other arms, docetaxel-carboplatin was associated with lower rates of grade 3 thrombocytopenia and anemia but a higher rate of grade 3 or 4 febrile neutropenia. CONCLUSION: There was no difference in TTP between the three arms, but survival was longer with pemetrexed-carboplatin compared with docetaxel-carboplatin. Enzastaurin did not add to the activity of pemetrexed-carboplatin.

Results of a Phase II study of weekly docetaxel and carboplatin in Stage IIIB (with effusion) or Stage IV non-small cell lung cancer patients age

This study explores if advanced NSCLC patients with ECOG PS 2 and age