Randomized trial of vitamin D3 to prevent worsening of musculoskeletal symptoms and fatigue in women with breast cancer starting adjuvant letrozole: The VITAL trial.

Abstract

9000 Background: Musculoskeletal (MS) pain and fatigue are common in women on adjuvant Aromatase Inhibitors (AIs) and lead to reduced compliance. Pilot studies suggest a positive impact of vit D on MS pain and disability from AIs. We conducted a bi-institutional, double blind, placebo controlled randomized trial to study the impact of 30,000 I.U of vit D3 in preventing worsening of MS pain and fatigue in women starting letrozole. Methods: Women with stage I-III breast cancer starting adjuvant AI and a 25(OH)D level of 40 ng/ml or less were eligible. Women with prior renal stones or hypercalcemia were excluded. All subjects received letrozole, plus standard dose vitD3 (600 IU) and calcium (1200 mg) daily, all provided by the study. Women were randomly assigned to 30,000 IU of oral vitD3 wkly (vitD arm) or matched placebos (PL arm) for 24 weeks. The following were assessed at baseline, 12 wks, and 24 wks (end of study): 1) 25OHD levels, 2) symptoms tools (BFI – Brief Fatigue Inventory, HAQII - Health Assessment Questionnaire II, Qualitative Joint Pain (none, mild, moderate, severe), BPI – Brief Pain Inventory) and 3) hand grip strength with a dynamometer. Results: 160 women (80/arm) were enrolled from 4/09 to 7/10. There were no differences between the two arms in demographics/tumor characteristics. Median age was 61, median BMI was 29.8 kg/m2. 43% had adjuvant chemotherapy. Median 25OHD (ng/ml) was 25 at baseline, 32 at 12 wks and 31 at 24 wks in the PL arm and 22, 53 and 57 in vitD arm. One patient in the PL arm developed mild hypercalcemia. There were no SAEs. 147 subjects were evaluable for efficacy. 3 subjects, all in the PL arm discontinued early due to a MS adverse event. At wk 24, a higher proportion of women in PL (51%) vs vitD arm (37%) had a protocol defined MS event (worsening of joint pain, disability from joint pain or discontinuation of Letrozole due to MS symptoms) (p=0.069). A significantly higher proportion of women in PL (72%) vs vitD arm (42%) had an adverse QOL event (worsening of pain, disability or fatigue) (p=<0.001). Conclusions: 30,000 IU/week of vitamin D3 is safe and results in decreased adverse QOL events from adjuvant aromatase inhibitors in women with breast cancer.