It is well established that the metabolically active form of
vitamin D, 1alpha,25-dihydroxyvitamin D3 (1alpha,25(
OH)2D3) plays a key role in the establishment and maintenance of the
calcium metabolism in the body. In addition to this classic effect of 1alpha,25(
OH)2D3, substantial evidence has emerged demonstrating that 1alpha,25(
OH)2D3 is able to regulate cell growth and differentiation in a number of different cell types, including
cancer cells. However, the clinical usefulness of 1alpha,25(
OH)2D3 is limited by its tendency to cause hypercalcaemia. Much effort has therefore been directed to identifying new
vitamin D analogues with potent cell regulatory effects, but with weaker effects on the
calcium metabolism than those of 1alpha,25(
OH)2D3. One of these new synthetic analogues is
Seocalcitol (
EB 1089). Despite being 50-200 times more potent than 1alpha,25(
OH)2D3 with respect to regulation of cell growth and differentiation in vitro as well as in vivo,
EB 1089 displays a reduced calcaemic activity in vivo compared to that of 1alpha, 25(
OH)2D3. These characteristics make
EB 1089 a potentially useful compound for the treatment of
cancer. Recent clinical evaluation of
EB 1089 has focused mainly on establishing a maximum tolerated dose in
cancer patients. Early results confirm that the low calcaemic activity observed in animals can be reproduced in the clinic. Furthermore,
EB 1089 has been shown to induce regression of tumours, especially in
hepatocellular carcinoma where complete remission has been obtained. In conclusion, the development of
EB 1089 as an anti-
cancer drug holds promise. However, its final evaluation must await the completion of ongoing controlled clinical trials.