Chronomodulated administration of chemotherapy in advanced colorectal cancer. A systematic review and meta-analysis

Aim: In this systematic review, the efficacy and safety of chronomodulated chemotherapy, defined as delivery of chemotherapy timed according to the human circadian rhythm, were assessed, and compared to continuous infusion chemotherapy for patients with advanced colorectal cancer. Methods: Electronic English language studies published until October 2020 were searched. Randomised Controlled Trials (RCTs) compared chronomodulated chemotherapy with non chronomodulated (Conventional) chemotherapy for management of advanced colorectal cancer were included. Main outcomes were the objective response rate (ORR) and system specific and overall toxicity related to chemotherapy. Electronic database search in Ovid Medline, Ovid Embase, Cochrane CENTRAL and the Cochrane Database of Systematic Review (CDSR). Results: In total, 7 RCTs including 1137 patients were analysed. Males represented 684 (60%) of the study population. The median age was 60.5 (range: 47.2 , 64) years. There is no significant difference between chronomodulated and conventional chemotherapy in ORR ((risk ratio (RR) 1.15; 95%CI [0.87,1.53]). There was no significant difference in gastrointestinal toxicity under the random effect model RR 1.02; CI 95% [0.68 , 1.51]. No significant difference was found regarding neurological and skin toxicities, (RR 0.64 ,95%CI [0.32 ,1.27]) and (RR 2.11, 95%CI [ 0.33, 13.32]), respectively. However, patients who received chronomodulated chemotherapy had fewer haematological toxicity, (RR 0.36, 95%CI [0.27, 0.48]). Conclusion: There was no overall difference in ORR or toxicity but haematologic, between chronomodulated and non chronomodulated chemotherapy used for patients with advanced colorectal cancer. Chronomodulated chemotherapy could be considered in patients at high risk of haematological toxicities.