Short‐duration Aerobic Exercise Improves Chemotherapy Induced Physical Dysfunction in Mice

Abstract

Chemotherapy regimens for colorectal cancer cause body weight loss, fatigue, and weakness that may persist long after treatment completion. While increased physical activity can help to mitigate these effects, low adherence to standard exercise prescriptions limits the therapeutic potential. Therefore, it is necessary to determine if an exercise threshold is required to improve chemotherapy toxicity. Gaps remain in our understanding of the extent of chemotherapy toxicities after treatment completion, and if a low dose of exercise is sufficient to improve chemotherapy‐induced dysfunction.PurposeTo examine the effects of exercise dose on body composition and physical function in mice during the recovery from Folfox chemotherapy.MethodsMale C57BL/6J mice (12wks) were injected with 4 cycles (1 cycle= 1 injection every other wk) of Folfox (FOL; 5FU 30mg/kg, Oxaliplatin 6mg/kg, Leucovorin 90mg/kg) or PBS. Mice were sacrificed 0wks (n=8) or 4wks (n=16) after the 4th cycle. Subsets of mice performed 14 sessions (6d/wk, 5% grade) of short‐ (15min/d; n=10) or long‐duration (60min/d; n=10) treadmill exercise during recovery. Body composition by MRI, treadmill run time to fatigue (RTF), and grip strength tests were performed pre, post, and after 4wks recovery.ResultsFOL treatment attenuated body mass gain (PBS 10%, FOL 3%) independent of food intake (p=0.586) or cage activity (p=0.801). Fat mass accumulation was decreased (PBS: 56%, FOL: ‐3%) with no changes in lean mass during treatment. During recovery, body mass remained suppressed (‐8%; p=0.022), and RTF (‐43%; p<0.01) and grip strength were reduced (‐9%; p=0.045) in FOL mice compared to PBS. Treadmill exercise improved body weight loss (3%; p=0.041) independent of fat mass. Long‐ compared to short‐duration exercise increased lean mass (p<0.01) in both treatment groups. Both short‐ and long‐duration exercise improved RTF (93%; p<0.01) without improving grip strength.ConclusionRepeated cycles of Folfox chemotherapy can induce persistent deficits in physical function and fat mass. Two weeks of short‐duration aerobic exercise was sufficient to reverse chemotherapy induced fatigue without improving strength. Future studies should examine if the combined effects of aerobic and resistance exercise can improve strength.