Korean J Hepatobiliary Pancreat Surg.  2015 Feb;19(1):1-5. 10.14701/kjhbps.2015.19.1.1.

An interim safety analysis of hepatocellular carcinoma patients administrating oral vitamin K with or without sorafenib

• Jung DH
• Hwang S
• Song GW
• Ryoo BY
• Kim N
• Tak E
• Hong HN

• KMID: 1802232
• DOI: http://doi.org/10.14701/kjhbps.2015.19.1.1

Abstract

BACKGROUNDS/AIMS
Vitamin K may plays a role in controlling hepatocellular carcinoma (HCC) cell growth. In this study, we intended to present 5-year experience of 72 patients receiving oral vitamin K with or without sorafenib. Its end-point was to evaluate the safety of combination therapy using sorafenib and vitamin K.
METHODS
An interim analysis was performed as a single-arm cross-sectional study, including 72 HCC patients who underwent liver resection or transplantation and administered oral vitamin K2 alone (n=47) or with sorafenib (n=25).
RESULTS
In all patients, administration of vitamin K2 analog 45 mg/day did not show any noticeable adverse side-effect during vitamin K therapy of 23.3+/-10.6 months, except for one patient who experienced skin rash at the third day of vitamin K therapy. In 25 patients receiving sorafenib and vitamin K for 6 months or longer, any noticeable adverse side-effect suspected of vitamin K origin was not identified yet. A small proportion of patients showed unexpectedly favorable anti-tumor effects after use of vitamin K with or without sorafenib.
CONCLUSIONS
Because add-on of oral vitamin K did not increase the adverse side-effects of sorafenib, a combination therapy with these two agents appears to be worthy of further clinical trial with an expectation of synergistic therapeutic effects.

Keyword

Vitamin K; Hepatocellular carcinoma; Sorafenib; Synergy; Metastasis

MeSH Terms

Carcinoma, Hepatocellular*
Cross-Sectional Studies
Exanthema
Humans
Liver
Neoplasm Metastasis
Vitamin K 2
Vitamin K*
Vitamin K
Vitamin K 2

Figure

• 

  Fig. 1 A liver resection patient demonstrating vitamin K-associated anti-tumor effect on multiple HCC metastasis. A 50 year-old female patient showed lumbar spine metastasis 4 months after resection of two small HCC lesions. (A) Despite radiotherapy, bone metastasis aggravated. Multiple lung and intrahepatic metastases occurred with high rise of HCC tumor markers (AFP 2070 ng/ml and DCP 610 mAU/ml). (B, C) Transarterial chemoembolization was performed to the intrahepatic recurrence. (D) After oral vitamin K was administered for 6 month, intrahepatic metastasis disappeared, lung metastasis were regressed and bone metastasis was stationary, with normalization of all tumor markers.

• 

  Fig. 2 A liver transplant recipient demonstrating vitamin K-associated anti-tumor effect on isolated pulmonary metastasis. A 58 year-old female recipient had isolated lung metastasis 18 months after transplantation, thus sorafenib and vitamin K were administered for 30 months. (A) Since lung mass progressed slowly, sorafenib was discontinued due to disease progression and only vitamin K was administered for more than 12 months. (B) The patient is currently doing well without any serious symptom despite very slow tumor progression.

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