Phase II trial of dose-dense chemotherapy followed by dose-intense erlotinib for patients with newly diagnosed metastatic non-small cell lung cancer

摘要

This phase?II study investigated dose-intense erlotinib maintenance after dose-dense chemotherapy for patients with metastatic non-small cell lung cancer and examined two cell cycle biomarkers. Patients with newly diagnosed metastatic non-small cell lung cancer received docetaxel 75?mg/m2 and cisplatin 75?mg/m2 on day?1 and pegfilgrastim on day?2 every 14?days for four?cycles. Patients then received erlotinib with initial doses based on smoking status. Doses were increased in 75?mg increments every two?weeks depending on toxicities until each patient's maximal tolerable dose (MTD) was achieved. Cyclin?D1 and D3 biomarkers were measured by immunohistochemistry. The objectives of the study were to evaluate time to progression (TTP) and overall survival (OS) for the entire population and biomarker subgroups. Forty-five patients were enrolled. Intra-patient erlotinib MTD ranged from 0 to 525?mg. Median MTD achieved in smokers was higher than in non-smokers (300?vs.?150?mg; P=0.019). TTP for the entire cohort was not significantly improved compared to historical controls. Patients with high cyclin?D1 expressing tumors demonstrated improved TTP on erlotinib (8.2?vs.?4.7?months; hazard ratio, 4.1; 95%?CI, 1.6-0.6; P=0.003) and improved OS (20.5?vs.?8.0?months; hazard ratio 2.8; 95%?CI, 1.2-6.3; P=0.016). Intratumoral cyclin?D3 expression did not impact clinical outcomes. Current smokers but not former smokers exhibit a higher erlotinib MTD. High cyclin?D1 expression was associated with favorable TTP and OS.