Sorafenib treatment in Child-Pugh A and B patients with advanced hepatocellular carcinoma: safety, efficacy and prognostic factors

Invest New Drugs. 2015 Jun;33(3):729-39. doi: 10.1007/s10637-015-0237-3. Epub 2015 Apr 12.

Abstract

Background: We aimed to evaluate the safety, efficacy and prognostic impact of baseline and early clinical markers in both Child-Pugh A and B patients with advanced hepatocellular carcinoma (HCC).

Methods: We prospectively studied 89 Japanese patients with HCC (Child-Pugh A, n = 59; Child-Pugh B, n = 30) who were started with sorafenib between May 2010 and July 2013.

Results: Frequency of sorafenib-related adverse events was almost similar between Child-Pugh score 5, 6, and 7 patients. The rate of liver dysfunction, including any grade encephalopathy, ≥ grade 3 ascites, or ≥ grade 3 bilirubin increased, in Child-Pugh score ≥8 group was significantly higher than that in the other groups. The median overall survival of Child-Pugh score 5, 6, 7 and ≥8 patients were 14.5, 11.1, 8.7 and 4.6 months, respectively. Patients in Child-Pugh score 6 had significantly longer OS than those in Child-Pugh score 7 (P = 0.049). Multivariate analysis identified macrovascular invasion (MVI), alpha-fetoprotein (AFP), Child-Pugh score and aspartate aminotransferase (AST) as baseline predictors of survival. However, extrahepatic metastasis (EHM) was not a significant prognostic factor. In addition, decrease in AFP level and development of hand-foot skin reaction within 4 weeks after sorafenib initiation were closely associated with favorable survival.

Conclusion: It is possible that not only Child-Pugh score 5 and 6 but also 7 patients are eligible for future clinical trials with sorafenib or similar drugs. Various survival predictors identified in this study might be considered as stratification factor. Although both MVI and EHM is a phenotype of advanced HCC, MVI should be discriminated from EHM because of the prognostic impact on survival in sorafenib-treated advanced HCC patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / pathology
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging
  • Niacinamide / adverse effects
  • Niacinamide / analogs & derivatives*
  • Niacinamide / therapeutic use
  • Phenylurea Compounds / adverse effects
  • Phenylurea Compounds / therapeutic use*
  • Prognosis
  • Sorafenib
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Phenylurea Compounds
  • Niacinamide
  • Sorafenib