PITTSBURGH, Jan. 20 -- A steroid drug enhances the ability of a vitamin D analogue to kill cancer while reducing a potentially serious side effect of vitamin D therapy, according to investigators at the University of Pittsburgh Cancer Institute (UPCI). Their findings on dexamethasone and the vitamin D derivative, 1,25-dihydroxyvitamin-D3, (1,25-D3), in an animal model are reported in the Jan. 21 issue of the Journal of the National Cancer Institute.

"We were very excited to find that not only did dexamethasone reduce hypercalcemia associated with 1,25-D3 , it actually improved the ability of 1,25-D3 to kill cancer cells in an animal model," noted Candace Johnson, Ph.D., study investigator, interim director for basic research at UPCI and co-director of UPCI's Molecular Oncology/Drug Discovery Program.

"We have previously shown that 1,25-D3 effectively halts the growth of cancer in animals, and we have conducted preliminary trials of this agent in men with advanced prostate and other cancers. However, the use of 1,25-D3 has been limited because this drug causes a potentially life-threatening increase of calcium in the blood," said Donald Trump, M.D., an investigator on the study, deputy director for clinical investigations at UPCI and director of the UPMC Health System's division of medical oncology.

UPCI investigators were among the first to describe the anti-tumor activity of vitamin-D compounds, or analogues, and showed that they arrest cancer growth in culture and in animals. While other researchers had previously shown the effect of vitamin D analogues in leukemia cells, Dr. Johnson and Dr.Trump were among the first to demonstrate the efficacy of these agents against solid tumors such as prostate cancer and head and neck cancers. Currently, the UPCI team is conducting a clinical protocol combining a steroid with 1,25-D3 for advanced cancer.

Dexamethasone appears to enhance 1,25
'"/>

Contact: Lauren Ward
wardla@a1.isd.upmc.edu
(412) 624-2607
University of Pittsburgh Medical Center
20-Jan-1998