Vitamin D Reduces Pain & Fatigue of Breast Cancer Treatment

The findings of the phase III randomized, placebo-controlled, double-blind VITAL study suggest that supplementation with vitamin D may be a viable option for reducing musculoskeletal pain and fatigue among women starting adjuvant aromatase inhibitor (AI) therapy for the treatment of breast cancer. The results were reported at ASCO by lead investigator Qamar J. Khan, MD, of the University of Kansas Medical Center.

The findings could have important implications for improving patient adherence to treatment. Around 50 percent of women who take adjuvant AIs for breast cancer report new or worsening musculoskeletal pain, and 18 percent to 30 percent report fatigue. "These are significant causes of women prematurely discontinuing therapy," Dr. Khan said during the presentation.

For the study, 147 women with stage I to III breast cancer were enrolled to receive letrozole therapy and a standard dose of vitamin D (600IU) plus calcium (1,200mg) daily. Patients were then randomly assigned to receive an additional 30,000IU/week of vitamin D3 or placebo. Patients were assessed for vitamin D levels at baseline and at weeks 12 and 24. Several system tools (questionnaires) allowed patients to monitor and rate symptoms.

Three patients, all in the placebo arm, discontinued therapy early due to musculoskeletal pain. In the vitamin D arm, blood levels increased from 22ng/mL at baseline to 53ng/mL at week 12 and 57ng/mL at week 24. In the placebo arm, blood levels of vitamin D increased from 25ng/mL at baseline to 32ng/mL at week 12 and 31ng/mL at week 24.

A higher proportion of women in the placebo arm (51 percent) experienced a protocol-defined musculoskeletal event, compared with 37 percent in the vitamin D arm, as evaluated with the Simple Descriptive Pain Intensity Scale. Using the quantitative Brief Pain Inventory, 61 percent of patients in the placebo arm and 38 percent in the vitamin D arm reported a musculoskeletal event (P=0.008).

The investigators also evaluated the incidence of an adverse quality-of-life event. A significantly higher percentage of women in the placebo arm (72 percent) reported a musculoskeletal event and fatigue, compared with 42 percent in the vitamin D arm (P<0.001).

Though the mechanism of action defining the benefit of vitamin D in this setting is unclear, Dr. Khan said, it is likely that AIs induce estrogen deprivation, thereby slowing local production of calcitriol (1,25-dihydroxycholecalciferol), which is important in limiting joint inflammation. Thus, stimulating higher doses of calcidiol (25-hydroxycholecalciferol) -- a prehormone produced in the liver as a result of hydroxylation of vitamin D, which is converted to calcitriol in the kidney -- is likely to be beneficial.

How long it takes for vitamin D supplementation to provide a benefit, and how sustainable the benefit will be, are still to be determined. The VITAL trial was designed to evaluate subjects only at baseline, 12 weeks, and 24 weeks, with primary and secondary end points evaluated upon the study's completion. Nevertheless, Dr. Khan said, it is noteworthy that patients who took additional vitamin D achieved high and presumably protective levels of serologic vitamin D at 12 weeks and maintained that level until the study's completion. This leveling off suggests that it may be feasible to load the body to sufficient vitamin D levels and then maintain that benefit in the long term, he said.

Vitamin D has long been recognized as essential for the formation, growth, and repair of bones and for normal calcium absorption and immune function. Short-term, high-dose vitamin D supplementation is being investigated for use in preventing progression of prostate cancer, and other studies have suggested benefits in colorectal and other types of cancer. According to the National Cancer Institute, "Whether vitamin D is associated with reduced risks of other cancers, including breast, prostate, and pancreatic cancers, remains unclear."

Because excessive vitamin D intake increases calcium levels, it can lead to calcinosis in soft tissues such as the kidneys, heart, and lungs, as well as hypercalcemia. Symptoms of excessive vitamin D intake include heart rhythm abnormalities, mental status changes (such as confusion), pain, conjunctivitis, anorexia, fever, chills, thirst, vomiting, and weight loss.