Indicators of sorafenib efficacy in patients with advanced hepatocellular carcinoma.

Abstract

AIM:

To determine significant indicators for the efficacy of sorafenib in patients with advanced hepatocellular carcinoma (HCC).

METHODS:

A total of 46 patients with Barcelona Clinic Liver Cancer stage C who received sorafenib for more than 30 d at the Iizuka Hospital from June 2009 to December 2012 were enrolled in this study. Multivariate and univariate analyses were performed to evaluate the associations of hepatic function according to Child-Pugh grade, location and size of the largest tumor and adverse events of sorafenib treatment, such as hand-foot syndrome (HFS), hypertension, diarrhea, and alopecia, with the efficacy of treatment, as measured by overall survival (OS) and time to progression (TTP).

RESULTS:

Patients included 39 men and 7 women whose ages ranged from 48 to 85 years (70.6 ± 9.6 years). HCC was classified according to etiology as follows: hepatitis C virus (n = 26), hepatitis B virus (n = 9), and other (n = 11). Liver function in patients was categorized as Child-Pugh grade A (n = 30) or B (n = 16). Tumors were categorized by size [< 5 cm (n = 33) or >5 cm (n = 13)] and the location of the largest tumor was used to categorize patients with intrahepatic (n = 28) or extrahepatic (n = 18) HCC. HFS, hypertension, diarrhea, and alopecia were present in 22 (47.8%), 19 (41.3%), 15 (32.6%) and 7 patients (15.2%), respectively. The median OS of all patients was 373 d and the median TTP was 112 d. The etiology of HCC did not correlate with the median OS and TPP. The median OS of patients with tumors < 5 cm was significantly longer than those with larger tumors (496 vs 245 d; HR = 0.19, 95%CI: 0.07-0.48; P < 0.01). According to the results of a multivariate analysis, the size of the largest tumor affected OS (HR = 0.22, 95%CI: 0.08-0.59; P < 0.01). The median TTP was significantly longer in patients with extrahepatic compared to intrahepatic major HCC (224 vs 98 d; HR = 0.32; 95%CI: 0.14-0.67; P < 0.01). The median TTP of patients with HFS was significantly longer than those without it (195 d vs 83 d; HR = 0.41, 95%CI: 0.20-0.82; P < 0.05), and the median TTP was significantly longer in patients with hypertension (195 d vs 84 d; HR = 0.43, 95%CI: 0.21-0.84; P < 0.05). According to the results of the multivariate analysis, extrahepatic major HCC (HR = 0.36, P < 0.01) and HFS (HR = 0.44, P < 0.05) prolonged TTP.

CONCLUSION:

Extrahepatic major HCC and HFS are associated with prolonged TTP and are useful indicators for judging the efficacy of sorafenib treatment.

• Authors: Masayoshi Yada, Akihide Masumoto, Kenta Motomura, Hirotaka Tajiri, Yusuke Morita, Hideo Suzuki, Takeshi Senju, Toshimasa Koyanagi
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 20 Issue 35 Pg. 12581-7 (Sep 21 2014) ISSN: 2219-2840 [Electronic] United States
• PMID: 25253961 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Phenylurea Compounds
• Protein Kinase Inhibitors
• Niacinamide
• Sorafenib

Topics

• Aged
• Aged, 80 and over
• Antineoplastic Agents (adverse effects, therapeutic use)
• Carcinoma, Hepatocellular (drug therapy, mortality, secondary)
• Disease Progression
• Disease-Free Survival
• Female
• Hand-Foot Syndrome (etiology)
• Humans
• Kaplan-Meier Estimate
• Liver Neoplasms (drug therapy, mortality, pathology)
• Male
• Middle Aged
• Multivariate Analysis
• Neoplasm Staging
• Niacinamide (adverse effects, analogs & derivatives, therapeutic use)
• Phenylurea Compounds (adverse effects, therapeutic use)
• Proportional Hazards Models
• Protein Kinase Inhibitors (adverse effects, therapeutic use)
• Retrospective Studies
• Risk Factors
• Sorafenib
• Time Factors
• Treatment Outcome
• Tumor Burden