The impact of exercise on tolerability of systemic treatment in metastatic colorectal cancer: A literature review.

Over half of patients with colorectal cancer (CRC) develop distant metastases and are often treated with multiple lines of systemic treatments, which can lead to severe toxicities. At least 40% of patients experience toxicity-induced treatment modifications in the first 3 months, which may impact anti-tumor effects. Exercise has the potential to limit toxicity and thereby prevent treatment modifications. This review discusses the role of physical exercise in limiting treatment toxicity in patients with metastatic CRC (mCRC). First an overview of the common toxicities of systemic treatment is presented. Second, the results from 15 observational studies examining associations of physical activity, fitness, and function with (toxicity-induced) treatment modification and survival outcomes are discussed, followed by the results from 8 exercise intervention studies in patients with mCRC. Finally, potential mechanisms of action by which exercise may impact toxicity of systemic treatments are described. Results highlight the potential benefits of exercise during systemic treatment. Although the number of studies is limited, observational studies found positive associations between physical activity, fitness, and function, and survival. Additionally, intervention studies revealed that exercise during systemic treatment is feasible and beneficial for patient-reported outcomes and physical fitness. Proposed mechanistic pathways by which exercise can limit toxicities including neurotoxicity, hematological toxicity, gastrointestinal toxicity, and fatigue are discussed. The potential of exercise on dermatological and immune-related toxicity of targeted and immunotherapy has yet to be investigated. Findings of this review emphasize the clear potential of exercise as an integral part of mCRC treatment, which should be confirmed in future trials. IMPLICATIONS FOR CANCER SURVIVORS: Incorporating physical exercise during systemic treatment for metastatic colorectal cancer has the potential to help reduce or even prevent toxicity-induced treatment modifications, which could benefit survival outcomes.