A phase 2 trial exploring the effects of high‐dose (10,000 IU/day) vitamin D₃ 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. Cancer 2010;116:284-91.

Oral paricalcitol (19-nor-1,25-dihydroxyvitamin D2) in women receiving chemotherapy for metastatic breast cancer

“…24 There was some improvement in pain with a reduction in the number of sites of pain. With ergocalciferol, most women showed only small increases in serum calcium but hypercalcemia occurred in two women, one of whom required hospitalization.…”

Diseases Affecting Bone Quality: Beyond Osteoporosis

“…In general, 50,000 IU of vitamin D 2 (ergocalciferol) can be given one to two times per week for 8 weeks, followed by a maintenance dose of vitamin D 3 of 1000 to 2000 IU/day [69,104]. Toxicity is rare even if a daily dosage of 10,000 IU vitamin D 3 is given for up to 4 months [3].…”

MECHANISMS IN ENDOCRINOLOGY: Vitamin D as a potential contributor in endocrine health and disease

“…This fine regulation is achieved through an interplay between parathyroid hormone (PTH), calcitonin, and 1,25(OH) 2 2 D and increased intestinal calcium absorption. While this form of hypercalcemia, promoted by the underlying parathyroid adenoma, is not strictly a manifestation of vitamin D toxicity, it is a form of hypersensitivity to higher doses of vitamin D that is important to consider, given how common parathyroid adenomas are (14).…”