Evaluation of dose-efficacy of sorafenib and effect of transarterial chemoembolization in hepatocellular carcinoma patients: a retrospective study.
BACKGROUND
Transarterial chemoembolization (TACE) and sorafenib are the therapeutic standard for intermediate and advanced stage hepatocellular carcinoma (HCC) patients respectively. High costs with adverse events (AE) of sorafenib might limit sorafenib dosage, further affecting therapeutic response. To attain greatest benefit, we evaluated the efficacy of different doses and effect of TACE during and after sorafenib discontinuation in patients representing Child-Pugh Classification Class A with venous or extra-hepatic invasion.


METHODS
A total 156 patients met the criteria and were divided into Groups I (n = 52) accepting 800 mg/day; II (n = 58) accepting 800 mg/day and reduced to 400 mg/day owing to AE; and III (n = 46) accepting 400 mg/day. TACE was performed during and after sorafenib discontinuation and therapeutic response bimonthly to four-monthly was rated thereafter.


RESULTS
Median duration of sorafenib treatment and patients' survival were 4.00 ± 0.45 and 7.50 ± 1.44 months in all cases; 2.50 ± 0.90 and 5.00 ± 1.10 months in Group I; 5.50 ± 1.27 and 16.50 ± 1.86 months in Group II; 4.00 ± 0.94 and 6.50 ± 2.49 months in Group III. Group II presented the best response and survival benefit (p = 0.010 and p = 0.011 respectively). Child-Pugh Classification score 5 (Hazard Ratio = 0.492, p = 0.049), absent AE (3.423, p = 0.015), tumor numbers ≤ 3 (0.313, p = 0.009), sorafenib duration ≤ 1 cycle (3.694, p = 0.004), and absent TACE (3.197, p = 0.008) significantly correlated with patient survival. TACE benefit appeared in separate and total cases during (p = 0.002, p = 0.595, p = 0.074, p = 0.002 respectively) and after discontinuation of sorafenib administration (p = 0.001, p = 0.034, p = 0.647, p = 0.001 respectively).


CONCLUSIONS
Low-dosage sorafenib not only appeared tolerable and lowered economic pressure but also provided satisfactory results. TACE benefited patient's survival during and after sorafenib discontinuation.
Division of Hepato-Gastroenterology, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung, 404, Taiwan.
Wang-De
WD
Hsiao
School of Medicine, China Medical University, Taichung, Taiwan.|Division of Hepato-Gastroenterology, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung, 404, Taiwan.
Cheng-Yuan
CY
Peng
Division of Hepato-Gastroenterology, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung, 404, Taiwan.
Po-Heng
PH
Chuang
Division of Hepato-Gastroenterology, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung, 404, Taiwan.
Hsueh-Chou
HC
Lai
Division of Hepato-Gastroenterology, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung, 404, Taiwan.
Ken-Sheng
KS
Cheng
Division of Hepato-Gastroenterology, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung, 404, Taiwan.
Jen-Wei
JW
Chou
School of Medicine, China Medical University, Taichung, Taiwan.|Division of Hepato-Gastroenterology, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung, 404, Taiwan.
Yang-Yuan
YY
Chen
Division of Hepato-Gastroenterology, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung, 404, Taiwan.
Cheng-Ju
CJ
Yu
Division of Hepato-Gastroenterology, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung, 404, Taiwan.
Chun-Lung
CL
Feng
Division of Hepato-Gastroenterology, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung, 404, Taiwan.
Wen-Pang
WP
Su
Division of Hepato-Gastroenterology, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung, 404, Taiwan.
Sheng-Hung
SH
Chen
School of Medicine, China Medical University, Taichung, Taiwan. garrydarkao@gmail.com.|Division of Hepato-Gastroenterology, Department of Internal Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung, 404, Taiwan. garrydarkao@gmail.com.
Jung-Ta
JT
Kao
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D006528:Carcinoma, Hepatocellular / Q000628:therapy*; D016461:Chemoembolization, Therapeutic / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010671:Phenylurea Compounds / Q000008:administration & dosage*; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D000077157:Sorafenib; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib
Dose-efficacy; Hepatocellular carcinoma patient; Sorafenib; TACE