Relative Dose Intensity of First-Line Chemotherapy and Overall Survival in Patients with Advanced Non-Small-cell Lung Cancer

Purpose The effects of chemotherapy dose intensity on survival in patients with advanced non-small-cell lung cancer (NSCLC) are poorly understood. We retrospectively analyzed dose delays/reduction, relative dose intensity (RDI), and the association between chemotherapy intensity and survival in advanced NSCLC. Methods This retrospective cohort study included adults with advanced lung cancer who received first-line myelosuppressive platinum-based chemotherapy (January 2007-December 2010) in ~ 230 US Oncology Network community practices. Dose delays >= 7 days, dose reductions >= 15%, and RDI relative to standard regimens were described. Overall survival (OS) was measured using Kaplan-Meier and Cox proportional hazard (PH) models. Results Among 3866 patients with advanced NSCLC, 32.4% experienced dose delays >= 7 days, 50.1% experienced dose reductions >= 15%, and 40.4% had RDI < 85%. Reduced RDI was also common regardless of baseline ECOG PS (ECOG PS >= 2, 56.2%; ECOG PS 0, 33.6%) and tumor subgroup (squamous cell carcinoma, 52.2%; adenocarcinoma, 36.0%). When stratified by chemotherapy intensity measures, significant OS differences were observed only for dose delays. Median (95% CI) OS was 1.02 years (0.96-1.12) for dose delays >= 7 days and 0.71 years (0.66-0.77) for dose delays < 7 days. In multivariable Cox PH analysis, dose delays >= 7 days (HR = 0.71; 95% CI = 0.63-0.80) and RDI >= 85% (HR = 1.18; 95% CI = 1.05-1.32) were significantly associated with decreased mortality. Conclusions Dose delays, dose reductions, and reduced RDI were common, and dose delays >= 7 days and high RDI were significantly associated with decreased mortality. These results can help identify potential risk factors and characterize the effect of chemotherapy dose modification strategies on mortality.