The effects of cytotoxic systemic chemotherapy for patients with advanced hepatocellular carcinoma who were not able to be treated with sorafenib

Abstract

Background/Aims Sorafenib has shown improvement of survival in patients with advanced hepatocellular carcinoma(HCC) when compared with placebo. However, whether sorafenib controls advanced stage of HCC better than systemic chemotherapy has not been elucidated. We aimed to compare the efficacy and safety of systemic cytotoxic chemotherapy with sorafenib.

Methods Medical records of 220 patients with measurable advanced HCC, who had not previously received systemic treatment, between January, 2007 and April, 2012, were reviewed. Among them, 95 patients who were treated with sorafenib were eligible. Another 20 patients who were treated with triweekly-regimen of adriamycin, cisplatin, and capecitabine were compared. They were not able to use sorafenib due to economic problem or nonexistence of sorafenib before 2008. Response, survival, time to progression, and toxicity were evaluated.

Results Baseline characteristics were similar between the treatment groups except serum bilirubin level (1.5±1.2 g/dL in sorafenib group vs 0.9±0.7g/dL in systemic chemotherapy group, p=0.017). 18.2%(10/55) and 45.5% (25/55) of patients achieved partial remission (PR) and stable disease (SD) in the sorafenib group. Similarly 20.0% (3/15) and 46.7% (7/15) of patients achieved PR and SD in systemic chemotherapy group. Best response rates were not significantly different between the groups (p=0.973). Overall median survival were 7.2 months(95% C.I 3.0-11.4) in the sorafenib group and 10.5 months(95% C.I 7.7-13.3) in systemic chemotherapy group, which showed no significant difference (p=0.89). Median time to progression were 6.8 months (95% C.I 4.3-9.2) in the sorafenib group and 3.3 months (95% C.I 2.5-4.0) in systemic chemotherapy group (p=0.22). When we adjusted the baseline Child-Pugh classification and the presence of major vessel invasion or distant metastastases, there was no significant difference in overall survival between the groups. By Cox regression analysis, baseline Child-Pugh classification and the presence of major vessel invasion effected on the survival (p=0.001 and p=0.01, respectively). There were more patients who harbored grade 3 and 4 toxicity in systemic chemotherapy group(70.0%) than sorafenib group (41.1%) (p=0.026). Hand foot skin reaction and neutropenia were the most frequent higher grade toxicity in the sorafenib and systemic chemotherapy group.

Conclusions Although head to head comparison could not be done, there clearly were some patients who showed good response to systemic cytotoxic chemotherapy. Further assessment needs to be done on the role of chemotherapy in patients who are intolerable or intractable to sorafenib.