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


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Liao
Cun
C
Department of Coloproctological Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China.
Li
Jing
J
Bin
Qiong
Q
Cao
Yunfei
Y
Gao
Feng
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D055870:Drug Chronotherapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017594:Publication Bias; D011785:Quality Assurance, Health Care; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
D000970:Antineoplastic Agents