Chronomodulated chemotherapy versus conventional chemotherapy for advanced colorectal cancer: a meta-analysis of five randomized controlled trials

The purpose of this study was to systematically compare the efficacy and safety of chronomodulated chemotherapy with conventional chemotherapy in patients with advanced colorectal cancer. Eligible studies were identified from electronic databases (Medline, Embase, and the Cochrane Library). The efficacy data included overall survival (OS) and objective response rate (ORR), and toxicities data contained diarrhea, vomiting and nausea, mucositis, asthenia, and peripheral sensory neuropathy. The meta-analysis was performed with the fixed-effect model or random-effect model according to heterogeneity. From 79 articles screened, five randomized controlled trials (RCTs) met the inclusion criteria contributing a total of 958 participants. There was a significant OS benefit (hazard ratio (HR) = 0.82; 95% confidence interval (CI) 0.69 to 0.97; P = 0.023) in favor of the chronomodulated chemotherapy. The ORR was not significantly different between two arms (relative risk = 1.27; 95% CI 0.88 to 1.83; P = 0.196). A higher incidence of grade 3/4 mucositis (odds ratio = 2.26, 95% CI 1.34 to 3.83; P = 0.724), asthenia (2.15, 1.30 to 3.56; P = 0.428), and a lower incidence of grade 3/4 neutropenia (0.26, 0.16 to 0.42; P = 0.641) were associated with the chronomodulated chemotherapy. The two arms were similar in terms of grade 3/4 diarrhea (1.10, 0.72 to 1.69; P = 0.756), vomiting and nausea (0.69, 0.42 to1.13; P = 0.239), and peripheral sensory neuropathy (0.56, 0.25 to 1.27, 0.164). Chronomodulated chemotherapy showed significant improvement in OS comparing with conventional chemotherapy. Side effects of the chronomodulated chemotherapy are predictable and manageable. But these results still need more high-quality RCTs for confirmation.