( ) 2012 12 6 6 Chin Arch Gen Surg (Electronic Edition), December 2012, Vol 6, No.6 507 陈东赵鹏陈伟殷晓煜肖伟锴梁力建 (sorafenib),, 52, Kaplan-Meier Cox, 52 14.2 (9.5 ~ 18.9) 22 (42.3%) (PD),2 (3.8%) (PR), (53.8%) (SD), 57.7% Cox, Child-Pugh A (HR = 0.3,P = 0.049), 2 (HR = 4.1,P = 0.049) (HR = 0.4, P = 0.026) 3 (17.3%) (7.7%), ; ; ; Sorafenib therapy in advanced hepatocellular carcinoma: a single center s experience CHEN Dong *, ZHAO Peng, CHEN Wei, YIN Xiao-yu, XIAO Wei-kai, LIANG Li-jian. * Department of Hepatobiliary Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China Corresponding author: LIANG Li-jian, E-mail: lianglj@medmail.com.cn Abstract Objective To investigate the efficacy and safety in sorafenib-treated HCC patients and to identify the prognostic factors. Methods In this retrospective study, 52 patients were given 400 mg of sorafenib b.d. aseline clinical parameters, adverse events (AEs) and survival data were collected. Kaplan- Meier and Cox regress analysis were performed to reveal the prognostic factors for survival. Results The median OS for all sorafenib-treated patients was 14.2 (9.5-18.9) months. Of all the patients, 2 (3.8%) had a partial response (PR), 22 had a progressive disease (PD) and the remaining had shown a stable disease (SD). The disease-control rate was 57.7%. The multivariate analysis revealed that patients of Child-Pugh class A (HR = 0.3, P = 0.049), PD less than 2 months (HR = 4.1,P = 0.049), and receiving other combined treatment modalities (HR = 0.4, P = 0.026) were independent prognostic factors for longer OS. The most common grade 3 toxicities were hand-foot syndrome (17.3%) and diarrhea (7.7%). Conclusions Sorafenib demonstrates a good outcome and tolerable toxicity in Chinese advanced HCC patients. The treatment modality and patients response to sorafenib therapy are associated with survival prognosis. Key words Sorafenib; Hepatocellular carcinoma; Prognosis; Safety SHARP ORIENTAL, HCC, [3-4] Child-Pugh, ECOG, DOI:10.3877/cma.j.issn.1674-0793.2012.06.010 : (10451008901004816); - (Y-2009-002;Y-2010-032) :510080, ( ); ( ) :, Email:lianglj@medmail.com.cn
508 ( ) 2012 12 6 6 Chin Arch Gen Surg (Electronic Edition), December 2012, Vol 6, No.6 [3], (time to progression, TTP) [5],TTP ;,, 2008 8, HCC, 2008 8 2011 11, 52 HCC [6] ECOG 2 2, Child-Pugh A, 12 400 mg, 2, 4 1 (National Cancer Institute s Common Terminology Criteria Adverse Events,NCI- CTCAE)3.0, 3, ( 400 mg, 1 ), 1 2, 2, 400 mg, 10 (TACE);6 ;3 ;5 1 (Response Evaluation Criteira in Solid Tumors, RECIST) 1.0, 8 (CT) (MR) 1, (overall survival, OS), TTP SPSS 17.0, t Fisher s Kaplan-Meier OS TTP, Log-rank, Cox OS (P < 0.10), P < 0.05 46 (88.5%), 45(21 ~ 71), ECOG 0 ~ 2, 0 29 (55.8%),1 18 (34.6%),2 5 (9.6%) 44 (84.6%) Child-Pugh A,8 (15.4%) Child-Pugh 9 (17.3%),6 (11.5%) (46.2%),12 (23.1%) CLC (,2010),40 (86.9%)C,44, 16, α- 7134(1.7 ~ 58 344)μg/L, 88(17 ~ 278)U/L TTP 5.2 (95%,3.2 ~ 6.8 ), OS 14.2 (95%,9.5 ~ 18.9 ),1 2 52%6%,32, 20 2 (3.8%) (partial response, PR), (53.8%) (partial response, SD),22 (42.3%) PD 57.7% ECOG Child-Pugh A CLC
( ) 2012 12 6 6 Chin Arch Gen Surg (Electronic Edition), December 2012, Vol 6, No.6 509 2 (P < 0.05) (1) 1 Log-rank () < 60 60 ECOG 0 1 2 Child-Pugh A α- (μg / L) < 400 400 CLC C AST (U / L) < 100 100 2 PD a 41 11 46 6 29 18 5 44 8 9 43 6 46 16 36 12 40 44 8 20 32 12.0 14.7 20.2 16.3 14.1 7.7 14.8 6.0 14.8 9.1 9.2 14.2 20.4 14.2-12.0 14.8 6.7 18.5 12.4 6.0 20.0 20.4 8.2 () 95% CI 5.7 ~ 18.3 5.3 ~.1 6.0 ~ 18.5 10.1 ~ 30.5 10.3 ~ 30.2 0.45 ~ 15.5 0 ~ 10.2 7.1 ~ 22.5 1.7 ~ 10.3 4.9 ~ 19.6 4.6 ~.9 0 ~ 21.2 7.3 ~ 17.3 0 ~ 15.1 8.5 ~ 19.8 7.5 ~ 17.0 0.6 ~ 30.1 6.1 ~ 22.2 0.86 ~ 23.7-9.5 ~ 18.9 6.7 ~ 22.9 1.9 ~ 11.4 9.8 ~ 16.5 6.6 ~.0 3.6 ~ 8.3 10.1 ~ 29.9 12.4 ~.3 6.0 ~ 10.4 P (Log-rank) :ECOG ; CLC ; AST ; PD ; a :, 10 ;, 6 ;, 3 ; 2, 5 0.7 0.397 0.044 < 0.001 0.544 0.960 0.057 0.275 0.814 0.026 0.014 0.753 < 0.001 0.025
510 ( ) 2012 12 6 6 Chin Arch Gen Surg (Electronic Edition), December 2012, Vol 6, No.6 Child-Pugh 2 PD 3 OS (2,1) 2 Cox HR 95% CI P (Cox ) ECOG 1.3 0.5 ~ 3.3 0.579 0 1 2 Child-Pugh 0.3 0.1 ~ 1.1 0.049 A 2.6 0.8 ~ 8.4 0.113 CLC 0.4 0.1 ~ 1.7 0.208 C 1.6 0.4 ~ 6.3 0.497 2 PD 4.1 1.8 ~ 9.4 0.001 0.4 0.2 ~ 0.9 0.026 45(86.5%) 1, (42.3%) (25.0%) 3 (5.8%), 8 (15.4%), 9(17.3%), 3 (5.8%),AST 4 (7.7%), 4 (7.7%) 12 3 (25.0%), (17.3%) (7.7%) 4 15 (.8%) 8,1,1,3,2 ( > 1000 U/L), HCC 14.2, 60%, SHARP (10.7,43%) [2] ; 5.2,SHARP (5.5 ) Child-Pugh (84.6% Child-Pugh A ), OS SHARP, (35,67.3%), (9,17.3%) HCC, HCC,ECOG Child-Pugh A CLC 2 PD, (P < 0.05), Child-Pugh 2 PD 3 OS,
( ) 2012 12 6 6 Chin Arch Gen Surg (Electronic Edition), December 2012, Vol 6, No.6 511 A C 1 Kaplan-Meier (OS) A. /. Chil-Pugh C. 2 / PD [7-9] Child-Pugh,,2 PD,,20.0 ( 2 PD 6.0 ), 20.4 ( 8.6 ) TACE 6 (68%);, 18.5 (95%,16.1 ~ 20.9 ) [10], 15 (15/) TACE, TACE,,, TACE, [3],, (42.3%) (25.0%) (25.0%) SHARP
512 ( ) 2012 12 6 6 Chin Arch Gen Surg (Electronic Edition), December 2012, Vol 6, No.6 21%, 40% [11], TACE,, Child-Pugh, HCC 1 2 3 4 5 6 7 8 9 10 11 Cheng AL, Kang YK, Chen Z, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase randomised, double-blind, placebo-controlled trial. Lancet oncol, 2009, 10(1): 25-34. Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. NEJM, 2008, 359(4): 378-390. Shim JH, Park JW, Choi JI, et al. Practical efficacy of sorafenib monotherapy for advanced hepatocellular carcinoma patients in a Hepatitis virusendemic area. J Cancer Res Clinic Oncol, 2009, 135(4): 617-625. aek KK, Kim JH, Uhm JE, et al. Prognostic factors in patients with advanced hepatocellular carcinoma treated with sorafenib: a retrospective comparison with previously known prognostic models. Oncology, 2011, 80(3-4): 167-174. Llovet JM, Di isceglie AM, ruix J, et al. Design and endpoints of clinical trials in hepatocellular carcinoma. JNCI, 2008, 100(10): 698-711. ruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology, 2005, 42(5): 1208-1236. Pinter M, Sieghart W, Hucke F, et al. Prognostic factors in patients with advanced hepatocellular carcinoma treated with sorafenib. Aliment Pharm Thera, 2011, 34(8): 949-959. Worns MA, Weinmann A, Pfingst K, et al. Safety and efficacy of sorafenib in patients with advanced hepatocellular carcinoma in consideration of concomitant stage of liver cirrhosis. J Clinic Gastroenterol, 2009, 43(5): 489-495.,,. [J/CD]. :, 2009, 3(2): 87-90. Cabrera R, Pannu DS, Caridi J, et al. The combination of sorafenib with transarterial chemoembolisation for hepatocellular carcinoma. Aliment Pharma Thera, 2011, 34(2): 205-213. Chen PJ, Furuse J, Han KH, et al. Issues and controversies of hepatocellular carcinoma-targeted therapy clinical trials in Asia: experts' opinion. Liver Int, 2010, 30(10): 1427-1438. ( :2012-08-16) ( : ) 陈东, 赵鹏, 陈伟, 等. 索拉非尼治疗晚期原发性肝癌的单中心经验 [J/CD]. 中华普通外科学文献 : 电子版, 2012,6(6):507-512.