Chronomodulated Administration of Chemotherapy in Advanced Colorectal Cancer: A Systematic Review and Meta-Analysis

Abstract

In this systematic review, the efficacy and safety of chronomodulated chemotherapy, defined as the delivery of chemotherapy timed according to the human circadian rhythm, were assessed and compared to continuous infusion chemotherapy for patients with advanced colorectal cancer.Electronic English-language studies published until October 2020 were searched. Randomised controlled trials (RCTs) comparing chronomodulated chemotherapy with non-chronomodulated (conventional) chemotherapy for the management of advanced colorectal cancer were included. The main outcomes were the objective response rate (ORR) and system-specific and overall toxicity related to chemotherapy. Electronic databases including Ovid Medline, Ovid Embase, Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Review were searched.In total, seven RCTs including 1,137 patients were analysed. Males represented 684 (60%) of the study population. The median age was 60.5 (range = 47.2-64) years. There was no significant difference between chronomodulated and conventional chemotherapy in ORR (risk ratio (RR) = 1.15; 95% confidence interval (CI) = 0.87-1.53). Similarly, there was no significant difference in gastrointestinal toxicity under the random effect model (RR = 1.02; 95% CI = 0.68-1.51). No significant difference was found regarding neurological and skin toxicities (RR = 0.64, 95% CI = 0.32-1.270 and RR = 2.11, 95% CI = 0.33-13.32, respectively). However, patients who received chronomodulated chemotherapy had less haematological toxicity (RR = 0.36, 95% CI = 0.27-0.48).In conclusion, there was no overall difference in ORR or haematologic toxicity between chronomodulated and non-chronomodulated chemotherapy used for patients with advanced colorectal cancer. Chronomodulated chemotherapy can be considered in patients at high risk of haematological toxicities.

Colorectal Cancer: Disease Process, Current Treatment Options, and Future Perspectives

“…On the contrary, a systematic review and meta-analysis of data from six randomized controlled trials involving 1347 patients on chronomodulated chemotherapies generally did not show any advantages over conventional therapies with regard to overall survival, objective response rate, or toxicity (Brenner et al, 2014;Huang et al, 2016) [4,184]. Other recent studies have confirmed these observations but found a reduction in hematologic toxicity in the chronomodulated therapy group (Nassar et al, 2023) [185]. Kinouchi and Sassone-Corsi (2020) [182] concluded that an information gap still exists regarding the existence of a common core clock connection between cancer and pluripotent stem cells that may elucidate the impact of the circadian clock on critical stages of cellular differentiation.…”

Chronobiology of the Tumor Microenvironment: Implications for Therapeutic Strategies and Circadian-Based Interventions

“…A RCT come from America indicated that chronotype-tailored light therapy could significantly improve the life quality of breast cancer patients receiving adjunct therapies [89]. Many studies support the positive effect of chronotherapy in cancer management, while some researchers doubt about this opinion [90]. Thus, higher-quality studies are still needed to demonstrate the effectiveness of chronotherapy.…”