48688
document
Differential effects of vitamin K1 on AFP and DCP levels in patients with unresectable HCC and in HCC cell lines . PURPOSE DCP is a useful HCC tumor marker , which reflects a defect in vitamin K metabolism . We tested the hypothesis that vitamin K treatment of HCC patients might suppress this marker and possibly AFP also . EXPERIMENTAL DESIGN HCC patients who had both elevated AFP and DCP were included . A phase I cohort was treated with escalating vitamin K1 intravenous weekly doses and a 27-patient phase II cohort was then treated with a fixed oral daily dose . RESULTS A maximum tolerated dose was not reached up to 100-fold the normal vitamin K1 dose . No toxicities were found up to 1,000 mg/infusion . In the phase II cohort , 93 % of patients had tumor marker responses by decreased DCP levels , but only 22 % had responses by decreased AFP levels . CT scans showed 11 % of patients had PRs , 59 % had stable tumors and 29.6 % had tumor progression . Mechanism studies showed that vitamin K1 induced phosphorylation of JNK and c-Jun and caspase-mediated apoptosis . CONCLUSIONS Vitamin K1 was non-toxic at high doses , strongly inhibited plasma DCP levels , but weakly suppressed AFP levels . The results provide evidence that the two tumor markers are not directly linked and that DCP levels may not reflect HCC cell growth , as DCP levels were decreased in patients without AFP change , and were suppressed in vitro at 1 % of the vitamin K1 concentration needed to inhibit AFP .
48689
Intervention_Pharmacological
vitamin K1
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Intervention_Pharmacological
vitamin K
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Intervention_Pharmacological
vitamin K1
48692
Intervention_Pharmacological
vitamin K1
48693
Intervention_Pharmacological
Vitamin K1
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Outcome_Other
maximum tolerated dose
48695
Outcome_Adverse-effects
toxicities
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Outcome_Physical
tumor marker responses
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Outcome_Physical
DCP levels
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Outcome_Physical
AFP levels .
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Outcome_Physical
PRs
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Outcome_Physical
stable tumors
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Outcome_Physical
tumor progression .
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Outcome_Physical
phosphorylation of JNK and c-Jun and caspase-mediated apoptosis .
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Participant_Condition
unresectable HCC
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Participant_Condition
HCC
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Participant_Condition
HCC
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Participant_Condition
HCC
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Participant_Sample-size
27-patient