The purpose of the study was to evaluate the efficacy and safety of vitamin D 3 at 4000 IU/day as a treatment option for aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) when compared with the usual care dose of 600 IU D 3 . We conducted a single site randomized, double-blind, phase 3 clinical trial in women with AIMSS comparing change in symptoms, reproductive hormones and AI pharmacokinetics. Postmenopausal women ≥18 years with stages I–IIIA breast cancer, taking AI and experiencing AIMSS [breast cancer prevention trial symptom scale-musculoskeletal (BCPT-MS) subscale ≥1.5] were admitted. Following randomization, 116 patients had a run-in period of 1 month on 600 IU D 3 , then began the randomized assignment to either 600 IU D 3 (n = 56) or 4000 IU D 3 (n = 57) daily for 6 months. The primary endpoint was a change in AIMSS from baseline (after 1 month run-in) on the BCPT-MS (general MS pain, joint pain, muscle stiffness, range for each question: 0 = not at all to 4 = extremely). Groups had no statistically significant differences demographically or clinically. There were no discernable differences between the randomly allocated treatment groups at 6 months in measures of AIMSS, pharmacokinetics of anastrozole and letrozole, serum levels of reproductive hormones, or adverse events. We found no significant changes in AIMSS measures between women who took 4000 IU D 3 daily compared with 600 IU D 3 . The 4000 IU D 3 did not adversely affect reproductive hormone levels or the steady state pharmacokinetics of anastrozole or letrozole. In both groups, serum 25(OH)D remained in the recommended range for bone health (≥30 ng/mL) and safety (<50 ng/mL).
Bibliographical noteFunding Information:
Research relating to this analysis was co-funded by Grants from the National Cancer Institute and the National Institutes of Health Office of Dietary Supplements (R21 CA149934) and the Park Nicollet Institute and Park Nicollet Foundation. This work was supported in part by NIHP30CA77598, using the following University of Minnesota Masonic Cancer Center Resource: Clinical Pharmacology and the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH UL1TR000114). The study was registered in Clinical Trials.gov (NCT01509079) and conducted under IND #114046. Trial Registration clinicaltrials.gov, identifier: NCT01509079.
- Aromatase inhibitors
- Breast cancer
- Vitamin D