Early Clinical Response after 2 Weeks of Sorafenib Therapy Predicts Outcomes and Anti-Tumor Response in Patients with Advanced Hepatocellular Carcinoma

• Published in: PloS one 2015-09, Vol.10 (9), p.e0138776-e0138776
• Main Authors: Kuzuya, Teiji, Ishigami, Masatoshi, Ishizu, Yoji, Honda, Takashi, Hayashi, Kazuhiko, Katano, Yoshiaki, Hirooka, Yoshiki, Ishikawa, Tetsuya, Nakano, Isao, Goto, Hidemi
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic agents; Biomarkers; Blood; Blood flow; Brain cancer; Cancer therapies; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - mortality; Clinical outcomes; Computed tomography; Disease-Free Survival; Dosage and administration; Drug dosages; Drug therapy; Female; Gastroenterology; Hepatocellular carcinoma; Hepatology; Hospitals; Humans; Inhibitor drugs; Liver; Liver cancer; Liver diseases; Liver Neoplasms - drug therapy; Liver Neoplasms - mortality; Male; Medical prognosis; Medicine; Middle Aged; Multivariate analysis; Niacinamide - administration & dosage; Niacinamide - analogs & derivatives; Oncology; Patients; Phenylurea Compounds - administration & dosage; Prognosis; Prospective Studies; Signal transduction; Solid tumors; Sorafenib; Studies; Survival; Survival Rate; Therapy; Time Factors; Tumors; University graduates; Vascular endothelial growth factor; α-Fetoprotein
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0138776

We evaluated the relationship between the early clinical response after 2 weeks of sorafenib therapy and the outcomes and anti-tumor response in patients with advanced hepatocellular carcinoma. Fifty-seven patients who had intrahepatic hypervascular hepatocellular carcinoma and Child-Pugh (CP) class A disease at baseline were enrolled in this prospective, multicenter, observational, non-interventional study. As an early clinical response after 2 weeks of sorafenib therapy, changes in intra-tumor blood flow on contrast-enhanced computed tomography (CE-CT), alpha-fetoprotein (AFP) levels, and remnant liver function were investigated. After 2 weeks of sorafenib therapy, there were 26 patients (45.6%) without disappearance of arterial tumor enhancement on CE-CT, 15 patients (26.3%) with an AFP ratio of >1.2, and seven patients (12.3%) with two or more increments in the CP score. Multivariate analysis showed that the absence of disappearance of arterial tumor enhancement on CE-CT, AFP ratio of >1.2, and two or more increments in the CP score after 2 weeks of sorafenib therapy were significant and independent predictors of worse survival. Upon scoring these three variables as "poor prognostic factors", patients with poor prognostic score 4, 3 or 2 (n = 17) had significantly worse outcomes and a significantly higher progressive disease (PD) rate based on modified Response Evaluation Criteria in Solid Tumors at 6 weeks after sorafenib therapy than those with poor prognostic score 1 or 0 (n = 40) (median overall survival: 194 days vs. 378 days; p = 0.0010, PD rate: 70.6% vs. 20.0%; p = 0.0003, respectively). Changes in intra-tumor blood flow on CE-CT, AFP levels, and remnant liver function after 2 weeks of sorafenib therapy may be useful for predicting the outcomes and anti-tumor response to sorafenib in patients with advanced hepatocellular carcinoma.