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A phase one study of the hepatic arterial administration of 1,25‐dihydroxyvitamin D 3 for liver cancers
Author(s) -
Finlay Ian G,
Stewart Graham J,
Ahkter Javed,
Morris David L
Publication year - 2001
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1046/j.1440-1746.2001.02398.x
Subject(s) - medicine , malignancy , colorectal cancer , gastroenterology , dose , cancer , endocrinology , liver function
Abstract Background and Aims: It is well established that exposure to 1,25‐dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) 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) 2 D 3 and analogs for the treatment of malignancy have been limited by the development of hypercalcemia. 1,25‐dihydroxyvitamin D 3 is principally excreted in bile following hepatic catabolism. This suggested the hypothesis that hepatic regional administration may allow high doses of 1,25(OH) 2 D 3 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) 2 D 3 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) 2 D 3 , 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) 2 D 3 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) 2 D 3 in the treatment of hepatic cancers to be realized.