Randomized Multicenter Placebo-Controlled Trial of Omega-3 Fatty Acids for the Control of Aromatase Inhibitor-Induced Musculoskeletal Pain: SWOG S0927

J Clin Oncol. 2015 Jun 10;33(17):1910-7. doi: 10.1200/JCO.2014.59.5595. Epub 2015 May 4.

Abstract

Purpose: Musculoskeletal symptoms are the most common adverse effects of aromatase inhibitors (AIs) and can result in decreased quality of life and discontinuation of therapy. Omega-3 fatty acids (O3-FAs) can be effective in decreasing arthralgia resulting from rheumatologic conditions and reducing serum triglycerides.

Patients and methods: Women with early-stage breast cancer receiving an AI who had a worst joint pain/stiffness score ≥ 5 of 10 using the Brief Pain Inventory-Short Form (BPI-SF) were randomly assigned to receive either O3-FAs 3.3 g or placebo (soybean/corn oil) daily for 24 weeks. Clinically significant change was defined as ≥ 2-point drop from baseline. Patients also completed quality-of-life (Functional Assessment of Cancer Therapy-Endocrine Symptoms) and additional pain/stiffness assessments at baseline and weeks 6, 12, and 24. Serial fasting blood was collected for lipid analysis.

Results: Among 262 patients registered, 249 were evaluable, with 122 women in the O3-FA arm and 127 in the placebo arm. Compared with baseline, the mean observed BPI-SF score decreased by 1.74 points at 12 weeks and 2.22 points at 24 weeks with O3-FAs and by 1.49 and 1.81 points, respectively, with placebo. In a linear regression adjusting for the baseline score, osteoarthritis, and taxane use, adjusted 12-week BPI-SF scores did not differ by arm (P = .58). Triglyceride levels decreased in patients receiving O3-FA treatment and remained the same for those receiving placebo (P = .01). No between-group differences were seen for HDL, LDL, or C-reactive protein.

Conclusion: We found a substantial (> 50%) and sustained improvement in AI arthralgia for both O3-FAs and placebo but found no meaningful difference between the groups.

Trial registration: ClinicalTrials.gov NCT01385137.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects*
  • Aromatase Inhibitors / administration & dosage
  • Aromatase Inhibitors / adverse effects*
  • Arthralgia / chemically induced
  • Arthralgia / drug therapy*
  • Arthralgia / prevention & control
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Chemotherapy, Adjuvant
  • Double-Blind Method
  • Drug Administration Schedule
  • Fatty Acids, Omega-3 / administration & dosage
  • Fatty Acids, Omega-3 / therapeutic use*
  • Female
  • Humans
  • Middle Aged
  • Musculoskeletal Pain / chemically induced
  • Musculoskeletal Pain / drug therapy*
  • Musculoskeletal Pain / physiopathology
  • Musculoskeletal Pain / prevention & control
  • Musculoskeletal System / physiopathology*
  • Neoplasm Staging
  • Patient Satisfaction
  • Postmenopause
  • Quality of Life
  • Self Report
  • Surveys and Questionnaires
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Aromatase Inhibitors
  • Fatty Acids, Omega-3

Associated data

  • ClinicalTrials.gov/NCT01385137