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


CONCLUSIONS
NX-DCP in combination with DCP could be a useful biomarker of sorafenib treatment for advanced HCC.
Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
Koji
K
Miyahara
Kazuhiro
K
Nouso
Yuki
Y
Morimoto
Takeshi
T
Tomoda
Sayo
S
Kobayashi
Yasuto
Y
Takeuchi
Hiroaki
H
Hagihara
Kenji
K
Kuwaki
Hideki
H
Ohnishi
Fusao
F
Ikeda
Yasuhiro
Y
Miyake
Shinichiro
S
Nakamura
Hidenori
H
Shiraha
Akinobu
A
Takaki
Kazuhide
K
Yamamoto
NX-des-γ-carboxyprothrombin; des-γ-carboxyprothrombin; hepatocellular carcinoma; sorafenib