Hepatic intra-arterial injection of 1,25-dihydroxyvitamin D3 in lipiodol: Pilot study in patients with hepatocellular carcinoma.
1,25-dihydroxycholecalciferol [1,25-(OH)2 D3] has been shown to have antiproliferative effects in a wide variety of cancer cell lines. In vivo studies, although often limited by the development of hypercalcemia, have also shown the potential usefulness of 1,25-(OH)2 D3 in inhibiting tumor growth. The potential usefulness of the drug has been hampered by the development of hypercalcemia. This pilot clinical study was designed to evaluate the preclinical results that have shown, locoregional administration of 1,25-(OH)2 D3 in lipiodol can prevent the development of hypercalcemia. Eight patients with refractory HCC were given a single intrahepatic arterial dose (50, 75 or 100 microg) of 1,25-(OH)2 D3 dissolved in 5 ml of lipiodol. Following this, for 4 weeks serum calcium, 1,25-(OH)2 D3, alpha-fetoprotein and a range of biochemical indices were monitored. While, in 3 patients the calcium levels exceeded the normal range, even at these extremely high doses, non of the patients developed grade 3 hypercalcemia. 1,25-(OH)2 D3 administration also led to transient stabilization of serum alpha-fetoprotein in these patients. The data obtained support the hypothesis that, in patients with HCC, locoregional delivery of 1,25-(OH)2 D3 in lipiodol can allow administration of supra-pharmacological doses of the drug without the development of hypercalcemia.
Morris
D L
DL
Department of Surgery, The University of New South Wales, St. George Hospital, Kogarah, Sydney, NSW 2217, Australia. david.morris@unsw.edu.au
Jourdan
J-L
JL
Finlay
I
I
Gruenberger
T
T
The
M P
MP
Pourgholami
M H
MH
D000368:Aged; D000369:Aged, 80 and over; D002117:Calcitriol / Q000627:therapeutic use*; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007269:Injections, Intra-Arterial; D007459:Iodized Oil / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D013997:Time Factors; D000509:alpha-Fetoproteins / Q000378:metabolism
D002120:Calcium Channel Agonists; D000509:alpha-Fetoproteins; D007459:Iodized Oil; D002117:Calcitriol; D002118:Calcium