Vitamin D Supplementation in Veterans With Early-Stage Prostate Cancer

Vitamin D promotes the differentiation of prostate cancer (PCa) cells, maintains the
differentiated phenotype of prostate epithelial cells, and can induce prostate cancer cell
death, raising the possibility that vitamin D deficiency over time promotes the progression
of subclinical PCa to clinical disease. These considerations support the use of vitamin D3 as
a chemopreventive agent.

We hypothesize that a daily dose of vitamin D3 (4,000 IU) taken for one year by Veterans
diagnosed with low-risk, early-stage PCa, who are eligible for active surveillance will: a)
result in a measurable decrease of serum PSA levels in a significant number of enrolled
subjects, and b) be associated with a stabilization or improvement of their PCa pathology, as
assessed through histological examination of prostate tissue biopsy specimens (Gleason score
and percent of positive biopsies) obtained at the end of the study, as part of their standard
medical care for active surveillance.

This VA Merit application proposes to conduct a randomized, placebo-controlled clinical study
aimed at measuring the efficacy of vitamin D3 (4000IU/day) supplementation in Veterans
diagnosed with early-stage prostate cancer, who elect to have their disease monitored through
active surveillance (before considering definitive therapy). The main objectives of this
proposed clinical study are as follows:

1. To determine whether a daily supplement of 4,000 IU of vitamin D3 taken for twelve
months will result in a measurable and significant decrease of serum PSA levels in
Veterans diagnosed with low-risk, early stage PCa (Gleason score 6, PSA 10, clinical
stage T1C or T2a), who elect to have their disease monitored through active surveillance
for at least one year.

2. To determine in enrolled Veterans the pathology status of their PCa by analyzing
prostate tissue biopsy specimens at the end of the study (Gleason score and percentage
of positive biopsies), and by comparing them with those obtained before enrollment in
this study, as part of their standard medical care.

The implementation of these proposed studies will allow us to assess whether vitamin D3
supplementation can be utilized as a chemopreventive regimen in Veterans diagnosed with
low-risk, early stage PCa, and provide a useful addition to active surveillance.

Inclusion Criteria:

- Male Veterans (> 18 years of age) recently diagnosed with low-risk PCa (histologically
documented adenocarcinoma of the prostate)

- A serum PSA value of up to 10.0 ng/ml, and a Gleason score of six or less (three or
less in either architectural pattern)

- For the purpose of eligibility, these additional criteria will be verified: *serum
creatinine 2.0 mg/dL

- serum phosphate (measured as phosphorus) > 2.3 and < 4.8 mg/dL

- serum calcium > 8.5 and < 10.5 mg/dL

Exclusion Criteria:

- Subjects with any concurrent malignancy, except non-melanoma skin cancer

- Subjects with a history of sarcoidosis

- Subjects with a history of high-dose (1,000 IU per day) vitamin D supplementation

- Subjects with a history of hypercalcemia

- Subjects who use lithium as a medication