Hormone refractory prostate cancer

Vitamin D and its metabolites, via binding to cellular vitamin D receptors, principally regulate bone homeostasis, but also have been observed to be potent growth inhibitors of neoplastic cells. Preclinical work strongly implies that vitamin D-based therapy could be effective in prostate cancer. Early clinical work with vitamin D has been complicated by its significant calcemic effects. 1alpha-OH-D2 is a vitamin D analog having less calcemic effects, but significant growth-inhibitory effects. Objective anti-tumor activity has been observed in a prostate cancer patient during an initial Phase I study of 1alpha-OH-D2.

This (University of Wisconsin) Phase II study involves daily use of 1alpha-OH-D2 in patients having advanced androgen-independent prostate cancer. The study observes transient mild hypercalcemia, without symptoms, in selected patients. No objective tumor responses are observed to date, and the study is too early to discuss the primary endpoint of time-to- treatment failure. Pilot correlative studies are underway to evaluate plasma-transforming growth factor. Beta1 levels, and T cell receptor-associated signal- transducing zeta chain expression, in peripheral mononuclear cells of study participants, are also underway, but without significant preliminary data. Observations to date continue to support the possibility that therapy with daily 1alpha-OH-D2 in androgen-independent prostate cancer could be effective.

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