Efficacy and Safety of Metronomic Capecitabine in Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Background and Objective Metronomic capecitabine has been found to be useful in several types of cancers such as pancreatic cancer, breast cancer, gastrointestinal cancers, nasopharyngeal carcinoma, metastatic colorectal cancer etc. This unique systematic literature review and meta-analysis was undertaken to assess the effectiveness and safety of metronomic capecitabine as a treatment regimen for hepatocellular carcinoma.

A systematic search of major databases was performed. Eight studies that dealt with the use of metronomic capecitabine for HCC were selected, seven were non-RCTs, and one was an RCT. Meta-analysis of these studies was performed using Review manager v5.3 and STATA 15.1 software. The pooled prevalence of OS, PFS, ORR, Grade 1-2 AE, Grade 3-4 AEs were determined, including publication bias and sensitivity analysis.

Eight studies met the inclusion criteria, combining the pooled data of 476 patients from safety and efficacy studies. The pooled prevalence of DCR and ORR achieved with metronomic capecitabine were 36% (95% CI 32-41) and 7% (95% CI 5-9) respectively. The median PFS and median OS were 3.57 months (95% CI 3.29-3.85) and 11.75 months (95% CI 10.56-12.95) respectively. The incidence of 3-4 grade AEs and 1-2 grade AEs were 38% (95% CI 32-44) and 73% (95% CI 67-79) respectively.

This meta-analysis highlights metronomic capecitabine as a potential second-line therapy for HCC. However, effective management of capecitabine’s side effects is essential. Competing Interest Statement The authors have declared no competing interest. Funding Statement There is no funding for this meta-analysis. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability All data produced in the present study are available upon reasonable request to the authors.