Hand-foot skin reaction is a beneficial indicator of sorafenib therapy for patients with hepatocellular carcinoma: a systemic review and meta-analysis

Background: Sorafenib remains the only standard first-line drug for advanced hepatocellular carcinoma (HCC). Hand-foot skin reaction (HFSR) is a very common side-effect in patients treated with sorafenib, and also affects the treatment schedule and quality of life. However, the association of HFSR and response of HCC to sorafenib remain unclear. Methods: Databases including PubMed, EMBASE, Web of Science and Cochrane Central Register of Controlled Trials were searched up to May 7th, 2017. Review Manager 5.3 software was adopted for performing meta-analyses, Newcastle-Ottawa Scale for assessing the bias of cohort studies, and GRADEprofler software for further assessing outcomes obtained from meta-analyses. Results: 1478 articles were reviewed, and 12 cohort studies with 1017 participants were included in the analyses. The pooled hazard ratio (HR) of overall survival is 0.45 (95% confidence interval (CI) 0.36, 0.55; P < 0.00001; I-2 = 35%). The pooled HR of time to progression is 0.41 (95% CI 0.28, 0.60; P < 0.00001; I-2 = 0%). Patients suffering HFSR had significantly better outcomes from sorafenib therapy than those without HFSR. Conclusions: The results indicate that HFSR is a beneficial indicator for HCC patients receiving sorafenib therapy. However, molecular mechanisms accounting for sorafenib-induced HFSR in HCC patients remain.