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

Author

Listed:
  • Teiji Kuzuya
  • Masatoshi Ishigami
  • Yoji Ishizu
  • Takashi Honda
  • Kazuhiko Hayashi
  • Yoshiaki Katano
  • Yoshiki Hirooka
  • Tetsuya Ishikawa
  • Isao Nakano
  • Hidemi Goto

Abstract

Background & Aims: 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. Methods: 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. Results: 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). Conclusions: 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.

Suggested Citation

  • Teiji Kuzuya & Masatoshi Ishigami & Yoji Ishizu & Takashi Honda & Kazuhiko Hayashi & Yoshiaki Katano & Yoshiki Hirooka & Tetsuya Ishikawa & Isao Nakano & Hidemi Goto, 2015. "Early Clinical Response after 2 Weeks of Sorafenib Therapy Predicts Outcomes and Anti-Tumor Response in Patients with Advanced Hepatocellular Carcinoma," PLOS ONE, Public Library of Science, vol. 10(9), pages 1-17, September.
    • Handle: RePEc:plo:pone00:0138776
    DOI: 10.1371/journal.pone.0138776
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