Predicting the treatment effect of sorafenib using serum angiogenesis markers in patients with hepatocellular carcinoma

Koji Miyahara, Kazuhiro Nouso, Takeshi Tomoda, Sayo Kobayashi, Hiroaki Hagihara, Kenji Kuwaki, Junichi Toshimori, Hideki Ohnishi, Fusao Ikeda, Yasuhiro Miyake, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Kazuhide Yamamoto

Research output: Contribution to journalArticle

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Abstract

Background and Aim: Sorafenib, the first agent demonstrated to have efficacy to improve the survival of patients with advanced hepatocellular carcinoma (HCC), is an active multikinase inhibitor affecting angiogenesis and tumor proliferation. We analyzed cytokines related to angiogenesis or cell proliferation, and tried to determine their utility as biomarkers of sorafenib treatment effect for HCC. Methods: Nine serum cytokines (angiopoietin-2 [Ang-2], follistatin, granulocyte colony-stimulating factor [G-CSF], hepatocyte growth factor [HGF], interleukin-8 [IL-8], leptin, platelet-derived growth factor-BB, platelet endothelial cell adhesion molecule-1, and vascular endothelial growth factor) were measured in 30 HCC patients treated with sorafenib, and the effects of treatment were compared using modified Response Evaluation Criteria in Solid Tumors. Results: All but IL-8 were significantly higher at baseline in patients with progressive disease. Progression-free survival was significantly shorter in patients with high levels of Ang-2, G-CSF, HGF, and leptin, and the hazard ratios were 2.51, 6.89, 2.55, and 4.14, respectively. As the number of cytokines at a high level increased, the treatment response deteriorated. Disease progression was seen in three of 12 (25.0%) patients with zero to two high biomarkers, two of six (33.3%) patients with 3-5 high biomarkers, and 10 of 12 (83.3%) patients with six to eight high biomarkers (P=0.008). The prognosis of all patients with eight high biomarkers was progressive disease. Conclusion: High levels of serum cytokines at baseline were correlated with poor effects of sorafenib treatment in patients with HCC.

Original languageEnglish
Pages (from-to)1604-1611
Number of pages8
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume26
Issue number11
DOIs
Publication statusPublished - 2011

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Hepatocellular Carcinoma
Biomarkers
Angiopoietin-2
Cytokines
Therapeutics
Hepatocyte Growth Factor
Granulocyte Colony-Stimulating Factor
Leptin
Interleukin-8
Follistatin
CD31 Antigens
sorafenib
Angiogenesis Inhibitors
Serum
Vascular Endothelial Growth Factor A
Disease-Free Survival
Disease Progression
Cell Proliferation
Survival
Neoplasms

Keywords

  • Angiogenesis
  • Biomarker
  • Cytokine
  • Hepatocellular carcinoma
  • Sorafenib

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

Predicting the treatment effect of sorafenib using serum angiogenesis markers in patients with hepatocellular carcinoma. / Miyahara, Koji; Nouso, Kazuhiro; Tomoda, Takeshi; Kobayashi, Sayo; Hagihara, Hiroaki; Kuwaki, Kenji; Toshimori, Junichi; Ohnishi, Hideki; Ikeda, Fusao; Miyake, Yasuhiro; Nakamura, Shinichiro; Shiraha, Hidenori; Takaki, Akinobu; Yamamoto, Kazuhide.

In: Journal of Gastroenterology and Hepatology (Australia), Vol. 26, No. 11, 2011, p. 1604-1611.

Research output: Contribution to journalArticle

Miyahara, Koji ; Nouso, Kazuhiro ; Tomoda, Takeshi ; Kobayashi, Sayo ; Hagihara, Hiroaki ; Kuwaki, Kenji ; Toshimori, Junichi ; Ohnishi, Hideki ; Ikeda, Fusao ; Miyake, Yasuhiro ; Nakamura, Shinichiro ; Shiraha, Hidenori ; Takaki, Akinobu ; Yamamoto, Kazuhide. / Predicting the treatment effect of sorafenib using serum angiogenesis markers in patients with hepatocellular carcinoma. In: Journal of Gastroenterology and Hepatology (Australia). 2011 ; Vol. 26, No. 11. pp. 1604-1611.
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T1 - Predicting the treatment effect of sorafenib using serum angiogenesis markers in patients with hepatocellular carcinoma

AU - Miyahara, Koji

AU - Nouso, Kazuhiro

AU - Tomoda, Takeshi

AU - Kobayashi, Sayo

AU - Hagihara, Hiroaki

AU - Kuwaki, Kenji

AU - Toshimori, Junichi

AU - Ohnishi, Hideki

AU - Ikeda, Fusao

AU - Miyake, Yasuhiro

AU - Nakamura, Shinichiro

AU - Shiraha, Hidenori

AU - Takaki, Akinobu

AU - Yamamoto, Kazuhide

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N2 - Background and Aim: Sorafenib, the first agent demonstrated to have efficacy to improve the survival of patients with advanced hepatocellular carcinoma (HCC), is an active multikinase inhibitor affecting angiogenesis and tumor proliferation. We analyzed cytokines related to angiogenesis or cell proliferation, and tried to determine their utility as biomarkers of sorafenib treatment effect for HCC. Methods: Nine serum cytokines (angiopoietin-2 [Ang-2], follistatin, granulocyte colony-stimulating factor [G-CSF], hepatocyte growth factor [HGF], interleukin-8 [IL-8], leptin, platelet-derived growth factor-BB, platelet endothelial cell adhesion molecule-1, and vascular endothelial growth factor) were measured in 30 HCC patients treated with sorafenib, and the effects of treatment were compared using modified Response Evaluation Criteria in Solid Tumors. Results: All but IL-8 were significantly higher at baseline in patients with progressive disease. Progression-free survival was significantly shorter in patients with high levels of Ang-2, G-CSF, HGF, and leptin, and the hazard ratios were 2.51, 6.89, 2.55, and 4.14, respectively. As the number of cytokines at a high level increased, the treatment response deteriorated. Disease progression was seen in three of 12 (25.0%) patients with zero to two high biomarkers, two of six (33.3%) patients with 3-5 high biomarkers, and 10 of 12 (83.3%) patients with six to eight high biomarkers (P=0.008). The prognosis of all patients with eight high biomarkers was progressive disease. Conclusion: High levels of serum cytokines at baseline were correlated with poor effects of sorafenib treatment in patients with HCC.

AB - Background and Aim: Sorafenib, the first agent demonstrated to have efficacy to improve the survival of patients with advanced hepatocellular carcinoma (HCC), is an active multikinase inhibitor affecting angiogenesis and tumor proliferation. We analyzed cytokines related to angiogenesis or cell proliferation, and tried to determine their utility as biomarkers of sorafenib treatment effect for HCC. Methods: Nine serum cytokines (angiopoietin-2 [Ang-2], follistatin, granulocyte colony-stimulating factor [G-CSF], hepatocyte growth factor [HGF], interleukin-8 [IL-8], leptin, platelet-derived growth factor-BB, platelet endothelial cell adhesion molecule-1, and vascular endothelial growth factor) were measured in 30 HCC patients treated with sorafenib, and the effects of treatment were compared using modified Response Evaluation Criteria in Solid Tumors. Results: All but IL-8 were significantly higher at baseline in patients with progressive disease. Progression-free survival was significantly shorter in patients with high levels of Ang-2, G-CSF, HGF, and leptin, and the hazard ratios were 2.51, 6.89, 2.55, and 4.14, respectively. As the number of cytokines at a high level increased, the treatment response deteriorated. Disease progression was seen in three of 12 (25.0%) patients with zero to two high biomarkers, two of six (33.3%) patients with 3-5 high biomarkers, and 10 of 12 (83.3%) patients with six to eight high biomarkers (P=0.008). The prognosis of all patients with eight high biomarkers was progressive disease. Conclusion: High levels of serum cytokines at baseline were correlated with poor effects of sorafenib treatment in patients with HCC.

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