Brief Article
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World J Gastroenterol. Jan 21, 2014; 20(3): 786-794
Published online Jan 21, 2014. doi: 10.3748/wjg.v20.i3.786
Predictors of survival in patients with established cirrhosis and hepatocellular carcinoma treated with sorafenib
Andrea L Inghilesi, Donatella Gallori, Lorenzo Antonuzzo, Paolo Forte, Daniela Tomcikova, Umberto Arena, Stefano Colagrande, Silvia Pradella, Bernardo Fani, Elena Gianni, Luca Boni, Giacomo Laffi, Francesco Di Costanzo, Fabio Marra
Andrea L Inghilesi, Donatella Gallori, Umberto Arena, Bernardo Fani, Giacomo Laffi, Fabio Marra, Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, I-50134 Florence, Italy
Lorenzo Antonuzzo, Francesco Di Costanzo, Oncologia Medica, Azienda Ospedaliero-Universitaria Careggi, I-50134 Florence, Italy
Paolo Forte, Elena Gianni, Gastroenterologia 2, Azienda Ospedaliero-Universitaria Careggi, I-50134 Florence, Italy
Daniela Tomcikova, Luca Boni, Centro per il Coordinamento delle Sperimentazioni Cliniche, Istituto Toscano Tumori, and Azienda Ospedaliero-Universitaria Careggi, I-50134 Florence, Italy
Stefano Colagrande, Silvia Pradella, Dipartimento di Scienze Biomediche, Sperimentali e Cliniche, Università degli Studi di Firenze, I-50134 Florence, Italy
Author contributions: Inghilesi AL, Gallori D, Antonuzzo L, Forte P, Arena U, Fani B, Gianni E, Laffi G, Di Costanzo F and Marra F recruited and followed the patients, and analyzed the data; Colagrande S and Pradella S analyzed CT and MR imaging; Tomcikova D and Boni L perfomed statistical analysis; Inghilesi AL and Marra F wrote the paper.
Supported by Grants from Associazione Italiana per la Ricerca sul Cancro (AIRC) and Istituto Toscano Tumori (ITT) to Marra F
Correspondence to: Fabio Marra, MD, PhD, Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, Largo Brambilla 3, I-50134 Florence, Italy.
Telephone: +39-055-7945425 Fax: +39-055-417123
Received: May 20, 2013
Revised: August 19, 2013
Accepted: August 28, 2013
Published online: January 21, 2014

AIM: To investigate in greater detail the efficacy and safety of sorafenib for the treatment of hepatocellular carcinoma (HCC) in patients with established cirrhosis.

METHODS: From October 2009 to July 2012 patients with an established diagnosis of cirrhosis and HCC treated with sorafenib were consecutively enrolled. According to the Barcelona Clinic Liver Cancer (BCLC) classification, patients were in the advanced stage (BCLC-C) or in the intermediate stage (BCLC-B) but unfit or unresponsive to other therapeutic strategies. Treatment was evaluated performing a 4-phase computed tomography or magnetic resonance imaging scan every 2-3 mo, and analyzed according to the modified Response Evaluation Criteria in Solid Tumors. Sorafenib was administered at 800 mg/d, until radiological progression or occurrence of unacceptable adverse events (AEs). Univariate and multivariate analyses identified predictors of 16-wk clinical benefit and overall survival.

RESULTS: Forty-four patients were enrolled, 15 had intermediate HCC and 14 a Child-Pugh score of B7. AEs caused treatment interruption in 19 patients (43%), and median treatment duration was shorter in this subset (5 wk vs 19 wk, P < 0.001) and in the BCLC-C subgroup (13 wk vs 40 wk, P = 0.015). No significant differences in the reason for treatment interruption or in treatment duration were found comparing patients in Child-Pugh class A vs B or in patients older or younger than 70 years. After 16 wk of treatment, 18 patients (41%) had stable disease or partial response. Patients with viral infection or BCLC-C were at higher risk of disease progression. ECOG, extrahepatic spread, macrovascular invasion, alpha-fetoprotein or alkaline phosphatase levels at admission were independent predictors of overall survival.

CONCLUSION: In patients with cirrhosis and HCC treated with sorafenib, AEs are a common cause of early treatment withdrawal. Vascular invasion and extrahepatic spread condition early response to treatment and survival. Baseline biochemical parameters may be helpful to identify patients at higher risk of shorter overall survival.

Keywords: Hepatocellular carcinoma, Sorafenib, Cirrhosis, Adverse events, Barcelona Clinic Liver Cancer

Core tip: The study provides information on the clinical characteristics and laboratory findings that predict survival in patients with hepatocellular carcinoma and established cirrhosis treated with sorafenib. This group of patients is particularly fragile and difficult to treat, and therapy with systemic agents, including sorafenib, requires careful monitoring. We report that parameters related to the tumor (extrahepatic spread, vascular invasion), common laboratory tests (alpha-fetoprotein or alkaline phosphatase) and patients characteristics (performance status) are significant predictors of overall survival in this group. These data provide important clinical information for the management of this type of patients.