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

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Abstract

Purpose

Aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) frequently occur in women being treated for breast cancer. Prior studies suggest high prevalence of vitamin D deficiency in breast cancer patients with musculoskeletal (MS) pain. We conducted a randomized, placebo-controlled trial to determine if 30,000 IU vitamin D3 per week (VitD3) would prevent worsening of AIMSS in women starting adjuvant letrozole for breast cancer.

Methods

Women with stage I–III breast cancer starting adjuvant letrozole and 25(OH)D level ≤40 ng/ml were eligible. All subjects received standard daily supplement of 1200 mg calcium and 600 IU vitamin D3 and were randomized to 30,000 IU oral VitD3/week or placebo. Pain, disability, fatigue, quality of life, 25(OH)D levels, and hand grip strength were assessed at baseline, 12, and 24 weeks. The primary endpoint was incidence of an AIMSS event.

Results

Median age of the 160 subjects (80/arm) was 61. Median 25OHD (ng/ml) was 25 at baseline, 32 at 12 weeks, and 31 at 24 weeks in the placebo arm and 22, 53, and 57 in the VitD3 arm. There were no serious adverse events. At week 24, 51% of women assigned to placebo had a protocol defined AIMSS event (worsening of joint pain using a categorical pain intensity scale (CPIS), disability from joint pain using HAQ-II, or discontinuation of letrozole due to MS symptoms) vs. 37% of women assigned to VitD3 (p = 0.069). When the brief pain inventory (BPI) was used instead of CPIS, the difference was statistically significant: 56 vs. 39% (p = 0.024).

Conclusions

Although 30,000 IU/week of oral vitamin D3 is safe and effective in achieving adequate vitamin D levels, it was not associated with a decrease in AIMSS events based on the primary endpoint. Post-hoc analysis using a different tool suggests potential benefit of vitamin D3 in reducing AIMSS.

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Abbreviations

AIMSS:

Aromatase Inhibitor-Associated Musculoskeletal Symptoms

AIST:

Aromatase Inhibitor Symptom Tool

AIs:

Aromatase Inhibitors

BFI:

Brief Fatigue Inventory

BPI:

Brief Pain Inventory

CPIS:

Categorical Pain Intensity Scale

FACT-B:

Functional Assessment of Cancer Therapy-Breast

HAQ-II:

Health Assessment Questionnaire II

MENQOL:

Menopause-specific Quality of Life

VITAL:

VITamin D treatment to prevent Arthralgia in women starting Letrozole

VitD3:

30,000 IU vitamin D3 per week

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Acknowledgements

Letrozole and funding for this study were provided by Novartis Pharmaceutical Corporation (East Hanover, NJ). Vitamin D3 (10,000 IU capsules) and matched, blinded placebo were provided by BTR Group, Inc. (Pittsfield, IL). Neither company was the sponsor for the trial; nor were they involved in any aspect of design and conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.

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Author notes

    Authors and Affiliations

    1. Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA

      Qamar J. Khan, Priyanka Sharma, Jennifer R. Klemp, Jennifer L. Nydegger & Carol J. Fabian

    2. Department of Radiation Oncology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS, 66160-7321, USA

      Bruce F. Kimler

    3. Cancer Center of Kansas, Wichita, KS, USA

      Pavan S. Reddy

    4. Laureate Institute for Brain Research, Tulsa, OK, USA

      Hung-Wen Yeh

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    1. Qamar J. Khan
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    Correspondence to Bruce F. Kimler.

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    Conflict of interest

    The following authors are without financial interests or conflicts of interest related to this trial: Kimler, Reddy, Klemp, Nydegger, and Yeh. Within the past three years, Dr. Khan has served as a consultant to Novartis Pharmaceutical Company, Inc. and Pfizer. Drs. Khan and Sharma have received during the past three years, via their institution, funding for support of research and clinical trials from the following companies: AstraZeneca; Bristol-Myers Squibb; Celgene, Inc.; Novartis Pharmaceutical Company, Inc.; Genentech-Roche, GlaxoSmithKline, and Pfizer. Study agent but no funding has been provided by DSM and Pfizer for trials conducted by Dr. Fabian.

    Ethical standards

    The conduct of the trial complies with the current laws of the United States of America.

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    Khan, Q.J., Kimler, B.F., Reddy, P.S. et al. Randomized trial of vitamin D3 to prevent worsening of musculoskeletal symptoms in women with breast cancer receiving adjuvant letrozole. The VITAL trial. Breast Cancer Res Treat 166, 491–500 (2017). https://doi.org/10.1007/s10549-017-4429-8

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    • DOI: https://doi.org/10.1007/s10549-017-4429-8

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