A phase II RCT of high-dose vitamin D supplementation for androgen deprivation therapy (ADT)-induced bone loss among older prostate cancer (PCa) patients.

Abstract

10113 Background: ADT is the most commonly used systemic therapy for treating locally advanced and metastatic PCa. ADT use causes hypogonadism, which can result in accelerated bone loss and fragility fractures. Vitamin D (VITD) may protect against bone loss; however it remains unclear if the recommended daily allowance (RDA) of VITD is sufficient to reduce bone loss or whether higher doses are needed. The aim of this phase II RCT was to collect preliminary data on the effect of high-dose VITD on bone mineral density (BMD) in ADT-treated PCa patients compared to the RDA of VITD. Methods: Older PCa patients (≥60 years old) with VITD insufficiency ( < 32 ng/ml), within 6 months of starting ADT and with 6 more planned months of ADT were randomized 1:1 to high-dose VITD (hVITD; 600 IU/daily plus 50,000 IU/weekly) or RDA of VITD (rVITD; 600 IU/daily plus placebo weekly) for 24 weeks. All subjects received 100% of the RDA for calcium (1,000 mg/day). BMD was assessed at the total hip (TH) and lumbar spine (LS) via DXA at pre- and post-intervention. ANCOVA was used to test the change in BMD between groups. Results: 59 PCa patients were accrued (85% white; mean age = 67.6). Serum analyses confirmed high compliance in both groups (25-OH VITD change: hVITD = +32.0 ng/ml vs rVITD = +4.3 ng/ml; p < 0.01). The safety of hVITD was similar to rVITD (Grade I hypercalcemia: hVITD: n = 1 vs rVITD: n = 0). Bone loss was significantly reduced for the hVITD group compared to rVITD group for total hip (TH BMD% change: hVITD = −1.5% vs rVITD = −4.1%; p = 0.02), with a trend for the femoral neck (BMD% change: hVITD = −1.7% vs rVITD = −4.3%; p = 0.06) and trochanter (BMD% change: hVITD = −1.0% vs rVITD = −2.8%; p = 0.10). There was no difference between groups for LS bone loss (LS BMD% change: hVITD = −0.8% vs rVITD = −0.6%; p = 0.75). Conclusions: High-dose VITD supplementation produced significantly greater reductions in hip BMD loss among older PCa patients receiving ADT compared to rVITD. Clinically, higher doses of VITD may be necessary to effectively prevent ADT-induced bone loss. A definitive phase III RCT is needed to confirm these findings. Funding: NCI R21CA175793, K07CA168911 & UG1CA189961. Bio-Tech Pharmacal Inc. supplied all agents. Clinical trial information: NCT02064946.