Timing of first-line cancer treatments – Early versus late – A systematic review of phase III randomized trials

Abstract

To conduct a systematic review and meta-analysis of all phase III randomized controlled trials comparing efficacy of early versus late first-line or initial treatments for cancer. A comprehensive literature search of MEDLINE and Cochrane library databases was performed (1966-2008). Data was extracted and pooled as per the methods recommended by the Cochrane Collaboration. Of the 570 identified studies, 10 (3811 patients) met inclusion criteria: three each in prostate cancer and multiple myeloma (MM), two in chronic lymphocytic leukemia (CLL), and one each in lung cancer, and follicular lymphoma. The analyses showed no survival benefit with early treatment except in prostate cancer (hazard ratio [HR]=1.23, 95% CI 1.11-1.37 p<0.001). There was no survival difference in MM (HR=0.92, 95% CI 0.56-1.52 p=0.74), CLL (HR=0.76, 95% CI 0.56-1.04 p=0.09), lung cancer (HR=0.95, 95% CI 0.72-1.24 p=0.71), or follicular lymphoma (HR=1, 95% CI 0.55-1.83 p=0.99). No statistically significant difference in response rate between early and late treatment was detected in any cancer type. Data shows that delaying cancer treatments does not necessarily compromise therapeutic outcomes except possibly in locally advanced prostate cancer. These findings provide a unique window to oncologists and patients to address time-sensitive issues if desired by patients.