Randomized Phase II Trial of Exercise, Metformin, or Both on Metabolic Biomarkers in Colorectal and Breast Cancer Survivors

Author:

Meyerhardt Jeffrey A1ORCID,Irwin Melinda L2ORCID,Jones Lee W34,Zhang Sui1,Campbell Nancy1,Brown Justin C15ORCID,Pollak Michael6,Sorrentino Alexandra1ORCID,Cartmel Brenda2,Harrigan Maura2,Tolaney Sara M1,Winer Eric1,Ng Kimmie1,Abrams Thomas1,Fuchs Charles S7ORCID,Sanft Tara2,Douglas Pamela S8,Hu Frank9,Ligibel Jennifer A1

Affiliation:

1. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA

2. Yale School of Public Health, Yale University, New Haven, CT

3. Memorial Sloan Kettering Cancer Center, New York, NY

4. Weil Cornell Medical Center, New York, NY

5. Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA

6. Oncology Department, McGill University and Segal Cancer Centre, Jewish General Hospital, Montreal, QC, Canada

7. Yale School of Medicine, Yale University, New Haven, CT

8. Duke University School of Medicine, Durham, NC

9. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA

Abstract

Abstract Background Observational data support inverse relationships between exercise or metformin use and disease outcomes in colorectal and breast cancer survivors, although the mechanisms underlying these associations are not well understood. Methods In a phase II trial, stage I–III colorectal and breast cancer survivors who completed standard therapy were randomly assigned to structured exercise or metformin or both or neither for 12 weeks. The primary outcome was change in fasting insulin levels; secondary outcomes included changes in other blood-based energetic biomarkers and anthropometric measurements. Analyses used linear mixed models. Results In total, 139 patients were randomly assigned; 91 (65%) completed follow-up assessments. Fasting insulin levels statistically significantly decreased in all three intervention arms (−2.47 μU/mL combination arm, −0.08 μU/mL exercise only, −1.16 μU/mL metformin only, + 2.79 μU/mL control arm). Compared with the control arm, all groups experienced statistically significant weight loss between baseline and 12 weeks (−1.8% combination arm, −0.22% exercise only, −1.0% metformin only, +1.55% control). The combination arm also experienced statistically significant improvements in the homeostatic model assessment for insulin resistance (−30.6% combination arm, +61.2% control) and leptin (−42.2% combination arm, −0.8% control), compared with the control arm. The interventions did not change insulin-like growth factor–1 or insulin-like growth factor binding protein–3 measurements as compared with the control arm. Tolerance to metformin limited compliance (approximately 50% of the participants took at least 75% of the planned dosages in both treatment arms). Conclusions The combination of exercise and metformin statistically significantly improved insulin and associated metabolic markers, as compared to the control arm, with potential greater effect than either exercise or metformin alone though power limited formal synergy testing. Larger efforts are warranted to determine if such a combined modality intervention can improve outcomes in colorectal and breast cancer survivors.

Funder

Transdisciplinary Research on Energetics and Cancer mechanism

National Cancer Institute

AKTIV Against Cancer

KavliTrust

Memorial Sloan Kettering Cancer Center

Douglas Gray Woodruff Chair Fund

Guo Shu Shi Fund

Anonymous Family Fund for Innovations in Colorectal Cancer

George Stone Family Foundation

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Oncology

Reference58 articles.

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