Analysis of Factors Influencing Discontinuation of Treatment and Development of Adverse Events with Sorafenib in Patients with Advanced Hepatocellular Carcinoma

Abstract

Sorafenib is an oral multikinase inhibitor for the treatment of patients with advanced hepatocellular carcinoma (HCC). However, it produces various adverse reactions (hand-foot syndrome, hypertension, diarrhea, etc.) that often lead to discontinuation of treatment, a clinical problem that needs to be addressed. In this study, we retrospectively reviewed the medical records of 50 patients with HCC who had been treated with sorafenib at Kyoto University Hospital to investigate factors influencing discontinuation of treatment continuation as well as development of adverse events. The overall rate for discontinuation of treatment (including treatment termination and dose reduction / interruption) due to adverse events was 56%, and that for treatment termination due to progressive disease was 30%. The frequency of discontinuation due to any reason within the first month was significantly higher in patients starting with 800 mg / day (19 / 35, 54.3%) than with 400 mg/day (3 / 15, 20.0%). In addition, the median duration of successful treatment with the starting dose was longer in patients on 400 mg/day than 800 mg / day (89 days vs. 29 days). The development of hand-foot syndrome (grade > 2) or diarrhea (any grade) was significantly associated with female sex and liver dysfunction at baseline (Child-Pugh B / C), respectively. In conclusion, when sorafenib is administered at 800 mg / day to HCC patients at high risk of adverse events, we should take measures for the early management of adverse effects and consider dose modification, which may help to sustain sorafenib therapy for a longer period with no discontinuation due to severe adverse events.