The use of single-agent sorafenib in the treatment of advanced hepatocellular carcinoma patients with underlying Child-Pugh B liver cirrhosis

被引:75
作者
Chiu, Joanne [1 ]
Tang, Yuen Fong [2 ]
Yao, Tzy-Jyun [2 ]
Wong, Ashley [1 ]
Wong, Hilda [1 ]
Leung, Roland [1 ]
Chan, Pierre [3 ]
Cheung, Tan To [4 ]
Chan, Albert C. [4 ]
Pang, Roberta [4 ,5 ]
Fan, Sheung-Tat [4 ,5 ,6 ]
Poon, Ronnie [4 ,5 ,6 ]
Yau, Thomas [1 ,4 ,5 ]
机构
[1] Queen Mary Hosp, Dept Med, Hong Kong, Hong Kong, Peoples R China
[2] Univ Hong Kong, Clin Trials Ctr, Hong Kong, Hong Kong, Peoples R China
[3] Ruttonjee Hosp, Dept Med, Hong Kong, Hong Kong, Peoples R China
[4] Queen Mary Hosp, Dept Surg, Hong Kong, Hong Kong, Peoples R China
[5] Univ Hong Kong, Ctr Canc Res, Hong Kong, Hong Kong, Peoples R China
[6] Univ Hong Kong, State Key Lab Liver Dis, Hong Kong, Hong Kong, Peoples R China
关键词
sorafenib; Child-Pugh A; Child-Pugh B; advanced hepatocellular carcinoma; adverse events; REFRACTORY SOLID TUMORS; FACTOR RECEPTOR INHIBITOR; PHASE-I; RAF KINASE; SAFETY; PHARMACOKINETICS; BAY-43-9006; STAGE;
D O I
10.1002/cncr.27543
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BACKGROUND: This study explored the efficacy, tolerability, and survival benefits of using sorafenib in patients with Child-Pugh class B (CPB) cirrhosis. METHODS: Patients with advanced hepatocellular carcinoma who were treated with sorafenib at Queen Mary Hospital, Hong Kong, China, were analyzed retrospectively. Treatment outcomes were analyzed according to their respective Child-Pugh status. Patients with CPB disease were further divided into CPB7 (those with a score of 7) and CPB8-9 (a score of 8 or 9) subgroups. RESULTS: The baseline demographic parameters were comparable between 108 patients with Child-Pugh class A (CPA) disease and 64 CPB patients. Both clinical benefit rate (21.3% vs 32.4% vs 14.8%; P = .23) and progression-free survival (median: 3.2 months vs 3.2 months vs 2.3 months; P = .26) were similar among CPA, CPB7, and CPB8-9 groups, respectively. The overall survival was different among these groups (P = .002) and showed a trend toward worse outcome in CPB patients: the median was 6.1, 5.4, and 2.7 months among CPA, CPB7, and CPB8-9 patients, respectively. The commonest grade 3/4 adverse events were hand-foot syndrome (13.5%), diarrhea (9.9%), and rash (7.0%). Grade 3/4 leukopenia, thrombocytopenia, and anemia occurred in 2.9%, 5.3%, and 8.8% of the patients, respectively. Overall, the 3 groups of patients experienced similar incidence of most of these adverse events. Nonetheless, CPB patients experienced more anemia (P = .01), gastrointestinal bleeding (P = .02), and hepatic encephalopathy (P = .02). CONCLUSIONS: CPA and CPB patients tolerated sorafenib similarly and derived similar clinical and progression-free survival benefit. Among CPB patients, most benefits were observed in patients with a score of 7. Nevertheless, CPB patients were more susceptible to developing cirrhotic complications, and thus more vigilant surveillance is needed. Cancer 2012. (c) 2012 American Cancer Society.
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收藏
页码:5293 / 5301
页数:9
相关论文
共 19 条
[1]   Phase II study of sorafenib in patients with advanced hepatocellular carcinoma [J].
Abou-Alfa, Ghassan K. ;
Schwartz, Lawrence ;
Ricci, Sergio ;
Amadori, Dino ;
Santoro, Armando ;
Figer, Arie ;
De Greve, Jacques ;
Douillard, Jean-Yves ;
Lathia, Chetan ;
Schwartz, Brian ;
Taylor, Ian ;
Moscovici, Marius ;
Saltz, Leonard B. .
JOURNAL OF CLINICAL ONCOLOGY, 2006, 24 (26) :4293-4300
[2]  
Abou-Alfa Ghassan K, 2011, Gastrointest Cancer Res, V4, P40
[3]   Phase I safety and pharmacokinetics of BAY 43-9006 administered for 21 days on/7 days off in patients with advanced, refractory solid tumours [J].
Awada, A ;
Hendlisz, A ;
Gil, T ;
Bartholomeus, S ;
Mano, M ;
de Valeriola, D ;
Strumberg, D ;
Brendel, E ;
Haase, CG ;
Schwartz, B ;
Piccart, M .
BRITISH JOURNAL OF CANCER, 2005, 92 (10) :1855-1861
[4]   Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial [J].
Cheng, Ann-Lii ;
Kang, Yoon-Koo ;
Chen, Zhendong ;
Tsao, Chao-Jung ;
Qin, Shukui ;
Kim, Jun Suk ;
Luo, Rongcheng ;
Feng, Jifeng ;
Ye, Shenglong ;
Yang, Tsai-Sheng ;
Xu, Jianming ;
Sun, Yan ;
Liang, Houjie ;
Liu, Jiwei ;
Wang, Jiejun ;
Tak, Won Young ;
Pan, Hongming ;
Burock, Karin ;
Zou, Jessie ;
Voliotis, Dimitris ;
Guan, Zhongzhen .
LANCET ONCOLOGY, 2009, 10 (01) :25-34
[5]   Safety and pharmacokinetics of the dual action Raf kinase and vascular endothelial growth factor receptor inhibitor, BAY 43-9006, in patients with advanced, refractory solid tumors [J].
Clark, JW ;
Eder, JP ;
Ryan, D ;
Lathia, C ;
Lenz, HJ .
CLINICAL CANCER RESEARCH, 2005, 11 (15) :5472-5480
[6]   Natural history and prognostic indicators of survival in cirrhosis: A systematic review of 118 studies [J].
D'Amico, G ;
Garcia-Tsao, G ;
Pagliaro, L .
JOURNAL OF HEPATOLOGY, 2006, 44 (01) :217-231
[7]   Risk of bleeding with vascular endothelial growth factor receptor tyrosine-kinase inhibitors sunitinib and sorafenib: a systematic review and meta-analysis of clinical trials [J].
Je, Youjin ;
Schutz, Fabio A. B. ;
Choueiri, Toni K. .
LANCET ONCOLOGY, 2009, 10 (10) :967-974
[8]   Sorafenib for hepatocellular carcinoma according to Child-Pugh class of liver function [J].
Kim, Jeong Eun ;
Ryoo, Baek-Yeol ;
Ryu, Min-Hee ;
Chang, Heung-Moon ;
Suh, Dong Jin ;
Lee, Han Chu ;
Lim, Young-Suk ;
Kim, Kang Mo ;
Kang, Yoon-Koo .
CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2011, 68 (05) :1285-1290
[9]   Sorafenib in advanced hepatocellular carcinoma [J].
Llovet, Josep M. ;
Ricci, Sergio ;
Mazzaferro, Vincenzo ;
Hilgard, Philip ;
Gane, Edward ;
Blanc, Jean-Frederic ;
Cosme de Oliveira, Andre ;
Santoro, Armando ;
Raoul, Jean-Luc ;
Forner, Alejandro ;
Schwartz, Myron ;
Porta, Camillo ;
Zeuzem, Stefan ;
Bolondi, Luigi ;
Greten, Tim F. ;
Galle, Peter R. ;
Seitz, Jean-Francois ;
Borbath, Ivan ;
Haussinger, Dieter ;
Giannaris, Tom ;
Shan, Minghua ;
Moscovici, Marius ;
Voliotis, Dimitris ;
Bruix, Jordi .
NEW ENGLAND JOURNAL OF MEDICINE, 2008, 359 (04) :378-390
[10]  
Marrero JA, 2011, J CLIN ONCOL S, V29