Page 234 - Vitamin D and Cancer

Chapter 10
Vitamin D and Prostate Cancer

Christine M. Barnett and Tomasz M. Beer

Abstract Following epidemiological observations that suggested links between
low vitamin D exposure and increased risk of prostate cancer, interest in clarify-
ing a potential role of this steroid hormone in prostate cancer has grown. While
the results have been mixed, epidemiologic studies have suggested that severe
vitamin D deficiency may increase the risk of clinically important prostate cancer.
Laboratory investigation provides clear evidence of the potential of vitamin D
receptor (VDR) ligands to induce growth arrest and promote apoptosis in a variety
of cancer models. Because there are hundreds of vitamin D responsive genes, mul-
tiple mechanisms for these observations have been proposed.
Prompted by clear evidence of dose-dependent antitumor effects, efforts to har-
ness this knowledge to improve patient outcomes has focused primarily on the
development of high dose calcitriol, often in combination with other anti-neoplastic
agents. After encouraging phase II results, the phase III effort failed when excess
deaths were reported in the experimental arm of a trial that compared calcitriol with
docetaxel to prednisone with docetaxel. In addition to targeting the vitamin D
receptor, the two arms of this study differed with respect to the dose, schedule, and
dose intensity of the chemotherapy agent and steroids, making definitive conclu-
sions about the potential of vitamin D receptor targeted therapy difficult. No pro-
spective randomized studies aimed at prostate cancer prevention have been
reported.
Continued efforts to target vitamin D signaling for prostate cancer prevention
and treatment are needed in light of the strong preclinical evidence supporting the
importance of this signaling pathway. Better understanding of the human prostate
cancer’s biologic heterogeneity in vitamin D sensitivity may allow for more robust
identification of ways in which vitamin D can be harnessed to help men who suffer
from this disease.

T.M. Beer (*)
OHSU, Knight Cancer Institute, 3303 SW Bond Ave, CH14R,
Portland, OR 97239, USA
e-mail: beert@ohsu.edu

D.L. Trump and C.S. Johnson (eds.), Vitamin D and Cancer, 221
DOI 10.1007/978-1-4419-7188-3_10, © Springer Science+Business Media, LLC 2011