Evaluation of the effect of sorafenib using serum NX-des-γ-carboxyprothrombin in patients with hepatocellular carcinoma

Koji Miyahara, Kazuhiro Nouso, Yuki Morimoto, Takeshi Tomoda, Sayo Kobayashi, Yasuto Takeuchi, Hiroaki Hagihara, Kenji Kuwaki, Hideki Ohnishi, Fusao Ikeda, Yasuhiro Miyake, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Kazuhide Yamamoto, Yoshitaka Takuma, Hiroyuki Takabatake, Youichi Morimoto, Shin Ichi Fujioka, Toshiya OsawaKazuya Kariyama, Junichi Toshimori, Haruhiko Kobashi, Hirokazu Miyatake, Shouta Iwadou, Yoshiyuki Kobayashi, Shuji Uematsu, Ryoichi Okamoto, Yasuyuki Araki, Masafumi Tatsukawa, Kazuhisa Yabushita, Toshinari Shimoe, Kohsaku Sakaguchi, Tatsuro Sakata, Toshihiko Kaneyoshi, Manabi Miyashita, Yasuhiro Makino, Akio Moriya, Masaharu Ando, Nobuyuki Baba, Tomonori Seno, Takuya Nagano, Koichi Takaguchi, Eiji Matsumoto, Hiroki Takayama

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Aim: Des-γ-carboxyprothrombin (DCP) is known to be increased by the use of sorafenib for the treatment of hepatocellular carcinoma (HCC), despite its therapeutic efficacy. In addition to the tumor progression, hypoxia that impairs vitamin K uptake is known to induce DCP and this mechanism may explain DCP elevation by sorafenib. In this study, we tried to evaluate the effect of sorafenib treatment using a new marker, NX-DCP, which is specific to vitamin K absence. Methods: Serum DCP and NX-DCP were measured in 50 consecutive HCC patients before and 1 week after starting sorafenib, and compared with the treatment effect using the modified Response Evaluation Criteria in Solid Tumors guidelines. Results: DCP and NX-DCP increased 1.58- (median, range 0.21-28.7) and 1.20-fold (median, range 0.41-14.2) after the administration of sorafenib, respectively. The increases of both markers were less than twofold in approximately half of the patients (low-elevation group). However, 12 patients showed over twofold increase of both DCP and NX-DCP (double-elevation group), and eight patients showed over twofold increase of DCP alone (DCP-elevation group). The disease control rate (DCR) of the DCP-elevation group (12.5%) was significantly lower than those of the double-elevation group (75.0%, P=0.020) and the low-elevation group (60.0%, P=0.042). Progression-free survival (PFS) was significantly shorter in the DCP-elevation group than in the double-elevation group (P=0.006) and the low-elevation group (P=0.001). Conclusion: NX-DCP in combination with DCP could be a useful biomarker of sorafenib treatment for advanced HCC.

Original languageEnglish
Pages (from-to)1064-1070
Number of pages7
JournalHepatology Research
Volume43
Issue number10
DOIs
Publication statusPublished - Oct 2013

Keywords

  • Des-γ-carboxyprothrombin
  • Hepatocellular carcinoma
  • NX-des-γ-carboxyprothrombin
  • Sorafenib

ASJC Scopus subject areas

  • Hepatology
  • Infectious Diseases

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