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

10 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

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Hepatocellular Carcinoma
Serum
Vitamin K
Therapeutics
Disease-Free Survival
sorafenib
Biomarkers
Guidelines

Keywords

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

ASJC Scopus subject areas

  • Hepatology
  • Infectious Diseases

Cite this

Evaluation of the effect of sorafenib using serum NX-des-γ-carboxyprothrombin in patients with hepatocellular carcinoma. / Miyahara, Koji; Nouso, Kazuhiro; Morimoto, Yuki; Tomoda, Takeshi; Kobayashi, Sayo; Takeuchi, Yasuto; Hagihara, Hiroaki; Kuwaki, Kenji; Ohnishi, Hideki; Ikeda, Fusao; Miyake, Yasuhiro; Nakamura, Shinichiro; Shiraha, Hidenori; Takaki, Akinobu; Yamamoto, Kazuhide; Takuma, Yoshitaka; Takabatake, Hiroyuki; Morimoto, Youichi; Fujioka, Shin Ichi; Osawa, Toshiya; Kariyama, Kazuya; Toshimori, Junichi; Kobashi, Haruhiko; Miyatake, Hirokazu; Iwadou, Shouta; Kobayashi, Yoshiyuki; Uematsu, Shuji; Okamoto, Ryoichi; Araki, Yasuyuki; Tatsukawa, Masafumi; Yabushita, Kazuhisa; Shimoe, Toshinari; Sakaguchi, Kohsaku; Sakata, Tatsuro; Kaneyoshi, Toshihiko; Miyashita, Manabi; Makino, Yasuhiro; Moriya, Akio; Ando, Masaharu; Baba, Nobuyuki; Seno, Tomonori; Nagano, Takuya; Takaguchi, Koichi; Matsumoto, Eiji; Takayama, Hiroki.

In: Hepatology Research, Vol. 43, No. 10, 10.2013, p. 1064-1070.

Research output: Contribution to journalArticle

Miyahara, K, Nouso, K, Morimoto, Y, Tomoda, T, Kobayashi, S, Takeuchi, Y, Hagihara, H, Kuwaki, K, Ohnishi, H, Ikeda, F, Miyake, Y, Nakamura, S, Shiraha, H, Takaki, A, Yamamoto, K, Takuma, Y, Takabatake, H, Morimoto, Y, Fujioka, SI, Osawa, T, Kariyama, K, Toshimori, J, Kobashi, H, Miyatake, H, Iwadou, S, Kobayashi, Y, Uematsu, S, Okamoto, R, Araki, Y, Tatsukawa, M, Yabushita, K, Shimoe, T, Sakaguchi, K, Sakata, T, Kaneyoshi, T, Miyashita, M, Makino, Y, Moriya, A, Ando, M, Baba, N, Seno, T, Nagano, T, Takaguchi, K, Matsumoto, E & Takayama, H 2013, 'Evaluation of the effect of sorafenib using serum NX-des-γ-carboxyprothrombin in patients with hepatocellular carcinoma', Hepatology Research, vol. 43, no. 10, pp. 1064-1070. https://doi.org/10.1111/hepr.12055
Miyahara, Koji ; Nouso, Kazuhiro ; Morimoto, Yuki ; Tomoda, Takeshi ; Kobayashi, Sayo ; Takeuchi, Yasuto ; Hagihara, Hiroaki ; Kuwaki, Kenji ; Ohnishi, Hideki ; Ikeda, Fusao ; Miyake, Yasuhiro ; Nakamura, Shinichiro ; Shiraha, Hidenori ; Takaki, Akinobu ; Yamamoto, Kazuhide ; Takuma, Yoshitaka ; Takabatake, Hiroyuki ; Morimoto, Youichi ; Fujioka, Shin Ichi ; Osawa, Toshiya ; Kariyama, Kazuya ; Toshimori, Junichi ; Kobashi, Haruhiko ; Miyatake, Hirokazu ; Iwadou, Shouta ; Kobayashi, Yoshiyuki ; Uematsu, Shuji ; Okamoto, Ryoichi ; Araki, Yasuyuki ; Tatsukawa, Masafumi ; Yabushita, Kazuhisa ; Shimoe, Toshinari ; Sakaguchi, Kohsaku ; Sakata, Tatsuro ; Kaneyoshi, Toshihiko ; Miyashita, Manabi ; Makino, Yasuhiro ; Moriya, Akio ; Ando, Masaharu ; Baba, Nobuyuki ; Seno, Tomonori ; Nagano, Takuya ; Takaguchi, Koichi ; Matsumoto, Eiji ; Takayama, Hiroki. / Evaluation of the effect of sorafenib using serum NX-des-γ-carboxyprothrombin in patients with hepatocellular carcinoma. In: Hepatology Research. 2013 ; Vol. 43, No. 10. pp. 1064-1070.
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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.",
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author = "Koji Miyahara and Kazuhiro Nouso and Yuki Morimoto and Takeshi Tomoda and Sayo Kobayashi and Yasuto Takeuchi and Hiroaki Hagihara and Kenji Kuwaki and Hideki Ohnishi and Fusao Ikeda and Yasuhiro Miyake and Shinichiro Nakamura and Hidenori Shiraha and Akinobu Takaki and Kazuhide Yamamoto and Yoshitaka Takuma and Hiroyuki Takabatake and Youichi Morimoto and Fujioka, {Shin Ichi} and Toshiya Osawa and Kazuya Kariyama and Junichi Toshimori and Haruhiko Kobashi and Hirokazu Miyatake and Shouta Iwadou and Yoshiyuki Kobayashi and Shuji Uematsu and Ryoichi Okamoto and Yasuyuki Araki and Masafumi Tatsukawa and Kazuhisa Yabushita and Toshinari Shimoe and Kohsaku Sakaguchi and Tatsuro Sakata and Toshihiko Kaneyoshi and Manabi Miyashita and Yasuhiro Makino and Akio Moriya and Masaharu Ando and Nobuyuki Baba and Tomonori Seno and Takuya Nagano and Koichi Takaguchi and Eiji Matsumoto and Hiroki Takayama",
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month = "10",
doi = "10.1111/hepr.12055",
language = "English",
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journal = "Hepatology Research",
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TY - JOUR

T1 - Evaluation of the effect of sorafenib using serum NX-des-γ-carboxyprothrombin in patients with hepatocellular carcinoma

AU - Miyahara, Koji

AU - Nouso, Kazuhiro

AU - Morimoto, Yuki

AU - Tomoda, Takeshi

AU - Kobayashi, Sayo

AU - Takeuchi, Yasuto

AU - Hagihara, Hiroaki

AU - Kuwaki, Kenji

AU - Ohnishi, Hideki

AU - Ikeda, Fusao

AU - Miyake, Yasuhiro

AU - Nakamura, Shinichiro

AU - Shiraha, Hidenori

AU - Takaki, Akinobu

AU - Yamamoto, Kazuhide

AU - Takuma, Yoshitaka

AU - Takabatake, Hiroyuki

AU - Morimoto, Youichi

AU - Fujioka, Shin Ichi

AU - Osawa, Toshiya

AU - Kariyama, Kazuya

AU - Toshimori, Junichi

AU - Kobashi, Haruhiko

AU - Miyatake, Hirokazu

AU - Iwadou, Shouta

AU - Kobayashi, Yoshiyuki

AU - Uematsu, Shuji

AU - Okamoto, Ryoichi

AU - Araki, Yasuyuki

AU - Tatsukawa, Masafumi

AU - Yabushita, Kazuhisa

AU - Shimoe, Toshinari

AU - Sakaguchi, Kohsaku

AU - Sakata, Tatsuro

AU - Kaneyoshi, Toshihiko

AU - Miyashita, Manabi

AU - Makino, Yasuhiro

AU - Moriya, Akio

AU - Ando, Masaharu

AU - Baba, Nobuyuki

AU - Seno, Tomonori

AU - Nagano, Takuya

AU - Takaguchi, Koichi

AU - Matsumoto, Eiji

AU - Takayama, Hiroki

PY - 2013/10

Y1 - 2013/10

N2 - 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.

AB - 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.

KW - Des-γ-carboxyprothrombin

KW - Hepatocellular carcinoma

KW - NX-des-γ-carboxyprothrombin

KW - Sorafenib

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