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J Gastroenterol Hepatol. 2001 Mar;16(3):333-7.

A phase one study of the hepatic arterial administration of 1,25-dihydroxyvitamin D3 for liver cancers.

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1
University of New South Wales, Department of Surgery, St George Hospital, Sydney, Australia.

Abstract

BACKGROUND AND AIMS:

It is well established that exposure to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) inhibits the proliferation of human colorectal cancer and hepatoma cell lines, both in vitro and in vivo. However, clinical trials of the administration of 1,25(OH)2D3 and analogs for the treatment of malignancy have been limited by the development of hypercalcemia. 1,25-dihydroxyvitamin D3 is principally excreted in bile following hepatic catabolism. This suggested the hypothesis that hepatic regional administration may allow high doses of 1,25(OH)2D3 to be administered for the treatment of liver cancers without producing hypercalcemia, caused by a clinically significant first pass effect. This phase one study investigates the effect of hepatic regional administration of 1,25(OH)2D3 on serum calcium levels, together with other markers of renal and liver function.

METHODS:

Six subjects with hepatic colorectal cancer metastases and one with primary hepatocellular cancer were given continuous hepatic arterial infusions of 1,25(OH)2D3, for periods of 1-4 weeks. Blood samples were taken regularly and assayed for calcium levels, liver function tests and urea and electrolyte levels.

RESULTS:

Patients remained normocalcemic at dosages of up to 10 mcg/day. No patient experienced any side-effects from the treatment.

CONCLUSIONS:

Administration of 1,25(OH)2D3 as a continuous hepatic arterial infusion allows a high dosage to be administered without inducing hypercalcemia. This route of administration may allow the potential of 1,25(OH)2D3 in the treatment of hepatic cancers to be realized.

[Indexed for MEDLINE]

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