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

Abstract

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.

Systematic Review of Tobacco Use after Lung or Head/Neck Cancer Diagnosis: Results and Recommendations for Future Research

“…Most studies were conducted in the United States (60.3%, n =79; e.g., (74, 99, 101, 114, 134)), with the next most common study locations being in Canada (7.6%, n =10; (30, 38, 39, 44, 65, 84, 97, 104, 147, 148)) and France (4.6%, n =6; (32, 37, 100, 108, 113, 146)). Most papers described cross-sectional studies (75.6%, n =99), but some described longitudinal studies (24.4%, n =32) (10, 35, 38, 42, 45, 46, 52-54, 56, 62, 65, 69, 73, 75, 76, 80, 84, 89, 90, 98, 100, 103, 104, 118, 121, 123, 126, 129, 135, 149, 152).…”

“…Ns denote number of studies in the analysis for Full Sample/Current Smokers at Cancer Diagnosis. Full Sample: Before Treatment includes data from (4, 10, 28, 32, 43, 45, 57, 59, 63-65, 68, 73, 74, 84, 99, 101, 102, 106, 108, 109, 111, 114, 127, 132, 134, 143, 148, 151, 154); During Treatment includes data from (34, 40, 75, 104, 110, 118, 121, 133, 145-147, 152) (33, 37, 38, 50, 78, 107, 124, 139, 150); After Treatment includes data from (29, 30, 49, 53, 58-60, 67, 69, 70, 79, 85-87, 89, 92, 97, 98, 100, 103, 105, 119, 122, 128, 138, 141); and Mixed includes data from (5, 41, 42, 46, 47, 52, 55, 61, 62, 73, 77, 80, 83, 90, 91, 93, 94, 96, 115, …”

Alternating Magnetic Field-Triggered Switchable Nanofiber Mesh for Cancer Thermo-Chemotherapy

“…Katsumata et al compared PTX administration paradigm of a weekly dose with the conventional one once every three week administration, for treatment of advanced epithelial ovarian cancer, and found that weekly administration was more effective [4]. This dose-dense concept has been applied for several different kinds of cancer such as primary and advanced breast cancer [25,26,27,28], ovarian cancer [28] and also NSCLC [29]. Thus, everything considered, our on-off switchable fiber system is very attractive for controllable chemotherapy.…”