Metronomic vinorelbine (oral) in combination with sorafenib in advanced non-small cell lung cancer

Background To date, biomarkers to predict benefit from anti-angiogenic therapy are still lacking. Sorafenib and metronomic oral vinorelbine combination was studied and changes in blood and DCE-MRI parameters were investigated as biomarkers for benefit. Material and methods Patients with advanced NSCLC were recruited to 3 successive cohorts. Each cohort was given a fixed metronomic (3 times a week) dose of oral vinorelbine at 60 mg/week, 90 mg/week, or 120 mg/week respectively. Within each cohort, patients received a starting dose of sorafenib at 200 mg bid for 4 weeks. In the absence of dose-limiting toxicities, each patient's dose of sorafenib was escalated to 400 mg bid for 4 weeks, 600 mg bid for 4 weeks and finally 800 mg bid. Biomarkers measured include DCE-MRI parameters, circulating endothelial cells (CECs), circulating endothelial progenitor cells (CEPs), and plasma thrombospondin (TSP-1). Results 48 evaluable patients were analyzed. There were 4 (8.9%) patients with partial response (PR) and 7 (15.2%) with cavitary response (CaR). Two subpopulations of CECs (CEChi, CEClo) were identified that trended in opposite directions during treatment, with CEChi demonstrating an upward trend in contrast to CEClo. Higher baseline CEChi and lower baseline blood flow (F) and fractional intravascular blood volume (V1) predicted for response. Multivariate analysis revealed a lower baseline V1, and dynamic changes of CEC during treatment (CEC increase, sum of CEChi and CEClo) predicted for improved survival. Conclusions Sorafenib and metronomic oral vinorelbine is active in advanced NSCLC. Baseline levels and changes in DCE parameters and CEC may be useful predictive biomarkers.