title: Development of sorafenib-related side effects in patients diagnosed with advanced hepatocellular carcinoma treated with sorafenib: a systematic-review and meta-analysis of the impact on survival.
abstract: ​Introduction: Clinical markers to predict the benefit from sorafenib in patients diagnosed with hepatocellular carcinoma (HCC) are lacking. A meta-analysis exploring the impact of development of sorafenib-related side effects on survival was conducted. Areas covered: Eligible studies included all clinical studies reporting on the survival/toxicity relationship in sorafenib-treated HCC patients. Data sources included Pub-Med, the Cochrane Controlled Trials Register, and Google scholar. After exclusion of ineligible studies, 16 studies were included in the analysis. Pooled hazard ratio (HR) for overall survival (OS) for patients developing diarrhoea vs. patients who did not was 0.42 (95% confidence interval (CI): 0.30-0.60; p < 0.00001); pooled HR for patients developing hypertension vs. those who did not was 0.46 (95% CI: 0.30-0.70; p = 0.0003); pooled HR for patients developing hand foot skin reaction vs. those who did not was 0.47 (95% CI: 0.35-0.62; p < 0.00001); pooled HR for OS for all types of skin toxicities was 0.51 (95% CI: 0.36-0.72; p = 0.0002); while pooled HR for OS for a combination of selected side effects (hypertension, HFS and diarrhoea) was 0.38 (95% CI: 0.30-0.48; p < 0.00001). No information was available regarding the impact of thyroid dysfunction or proteinuria. Expert commentary: This analysis of data demonstrated that the occurrence of sorafenib-related side effects (such as diarrhoea, hypertension and skin toxicities) is associated with a better OS in sorafenib-treated HCC patients.
authors.affiliation: a Clinical Oncology Department, Faculty of Medicine , Ain Shams University , Cairo , Egypt.
authors.forename: Omar
authors.initials: O
authors.lastname: Abdel-Rahman
authors.affiliation: b Medical Oncology Department , The Christie NHS Foundation Trust , Manchester , UK.
authors.forename: Angela
authors.initials: A
authors.lastname: Lamarca
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016009:Chi-Square Distribution; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives*; D016017:Odds Ratio; D010671:Phenylurea Compounds / Q000009:adverse effects*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D012307:Risk Factors; D000077157:Sorafenib; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D000077157:Sorafenib
keywords: HCC; HFS; diarrhoea; hypertension; sorafenib