title: A phase 2 trial exploring the effects of high-dose (10,000 IU/day) vitamin D(3) in breast cancer patients with bone metastases.
abstract: BACKGROUND
  Vitamin D deficiency has potential roles in breast cancer etiology and progression. Vitamin D deficiency has also been associated with increased toxicity from bisphosphonate therapy. The optimal dose of vitamin D supplementation is unknown, but daily sunlight exposure can generate the equivalent of a 10,000-IU oral dose of vitamin D(3). This study therefore aimed to assess the effect of this dose of vitamin D(3) in patients with bone metastases from breast cancer.
  
  
  METHODS
  Patients with bone metastases treated with bisphosphonates were enrolled into this single-arm phase 2 study. Patients received 10,000 IU of vitamin D(3) and 1000 mg of calcium supplementation each day for 4 months. The effect of this treatment on palliation, bone resorption markers, calcium metabolism, and toxicity were evaluated at baseline and monthly thereafter.
  
  
  RESULTS
  Forty patients were enrolled. No significant changes in bone resorption markers were seen. Despite no change in global pain scales, there was a significant reduction in the number of sites of pain. A small but statistically significant increase in serum calcium was seen, as was a significant decrease in serum parathyroid hormone. Treatment unmasked 2 cases of primary hyperparathyroidism, but was not associated with direct toxicity.
  
  
  CONCLUSIONS
  Daily doses of 10,000 IU vitamin D(3) for 4 months appear safe in patients without comorbid conditions causing hypersensitivity to vitamin D. Treatment reduced inappropriately elevated parathyroid hormone levels, presumably caused by long-term bisphosphonate use. There did not appear to be a significant palliative benefit nor any significant change in bone resorption.
authors.affiliation: Department of Medical Oncology, Princess Margaret Hospital, Toronto, Ontario, Canada.
authors.forename: Eitan
authors.initials: E
authors.lastname: Amir
authors.forename: Christine E
authors.initials: CE
authors.lastname: Simmons
authors.forename: Orit C
authors.initials: OC
authors.lastname: Freedman
authors.forename: George
authors.initials: G
authors.lastname: Dranitsaris
authors.forename: David E C
authors.initials: DE
authors.lastname: Cole
authors.forename: Reinhold
authors.initials: R
authors.lastname: Vieth
authors.forename: Wei S
authors.initials: WS
authors.lastname: Ooi
authors.forename: Mark
authors.initials: M
authors.lastname: Clemons
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D001862:Bone Resorption / Q000188:drug therapy; D001943:Breast Neoplasms / Q000473:pathology*; D002762:Cholecalciferol / Q000008:administration & dosage* / Q000009:adverse effects; D019587:Dietary Supplements; D004164:Diphosphonates / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007011:Hypoparathyroidism / Q000188:drug therapy; D008875:Middle Aged; D010146:Pain / Q000188:drug therapy
chemical_list: D015415:Biomarkers; D004164:Diphosphonates; D002762:Cholecalciferol