Kleckner, I.R., Kamen, C., Gewandter, J.S., Mohile, N.A., Heckler, C.E., Culakova, E., . . . Mustian, K.M. (2018). Effects of exercise during chemotherapy on chemotherapy-induced peripheral neuropathy: A multicenter, randomized controlled trial. Supportive Care in Cancer, 26, 1019–1028.

To explore the effect of a moderate-intensity, home-based, six-week progressive walking and resistance exercise program on chemotherapy-induced peripheral neuropathy (CIPN) symptoms, and factors that predict CIPN and moderate the effects of exercise on CIPN, in patients with cancer receiving taxane-, platinum-, or vinca alkaloid-based chemotherapy, compared to standard of care.

Control condition: Standard care wait list control. Received the same number of follow-up visits as the exercise group.

Exercise for Cancer Patients (EXCAP) intervention: Moderate-intensity, home-based, six-week progressive walking and resistance exercise program developed by the American College of Sports Medicine.

• Walking dose: Low/moderate-intensity (60%-85% heart rate reserve) daily. Tailored based on individual’s baseline steps per day; increase steps per day by 5%-20% each week
• Resistance training dose: Theraband (resistance at 3-5 rating of perceived exertion [RPE]) daily. Ten required and four optional upper and lower extremity exercises (e.g., squats, biceps curl). Tailored progression up to four sets of 15 reps and in theraband resistance each week 
• Duration: Six weeks
• Materials provided to the patient: Pedometer, three resistance bands, and manual
• Visits: One 60-minute intervention orientation session in the clinic on the patient’s first day of chemotherapy
• Interventionist: Clinical research associates who had no professional exercise qualifications but received brief training in the EXCAP by an ACSM-certified exercise professional

• N = 355   
• AGE: Mean age = 55.8 years (SD = 10.8; range = 28-79 years)
• MALES: 7.32%  
• FEMALES: 92.68%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Stages I-IV of primarily breast (79%) but also lymphoma, colon, lung, and other types of cancer; receiving taxanes (61.4%), platinums (11%), and/or vinca alkaloids (5%), but chemotherapy naïve at baseline. Mean baseline neuropathy on 0-10 NRS was 0.9 (SD = 1.9) (numbness and tingling) and 0.8 (SD = 1.9) (hot/coldness in hands/feet); 29.6% of patients reported any numbness and tingling in hands/feet.
• OTHER KEY SAMPLE CHARACTERISTICS: Inactive (in precontemplation, contemplation, or preparation per the Exercise Stages of Change) at baseline. Karnofsky performance status ≥ 70% (mean = 94.6, SD = 7); 85.91% received prior surgery; less than 3% received XRT and/or hormone therapy; 67% were employed and 64.22% were married.

• SITE: Multi-site   
• SETTING TYPE: Home    
• LOCATION: James P. Wilmot Cancer Center at University of Rochester Medical Center, NY, and 20 NCORP community oncology practice sites throughout the United States.

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Elder care, palliative care

Secondary data analysis of a multi-site non-blinded randomized controlled trial (originally designed to evaluate the effects of the intervention on fatigue)

Collected at baseline and after the intervention (at six weeks):

• CIPN symptoms: 0-10 NRS of (a) numbness/tingling, and (b) hot/coldness in hands/feet in the past seven days
• Exercise adherence: Daily exercise diary self-reported pedometer steps, minutes of resistance exercise, and RPE rated on 1-10 scale

CIPN symptoms (NRS) progressed in both groups throughout chemotherapy (all p ≤ 0.027). However, NRS of numbness/tingling (p = 0.061; β = 0.42, CI [-0.85, 0.02]) and hotness/coldness in the hands/feet (p = 0.045; β = -0.46; CI [-0.01, -0.91]) were less severe in the intervention group at six weeks; 36.5% of intervention group participants and 49.2% of control group participants reported some numbness/tingling (NRS > 0) at six weeks. 

Baseline neuropathy (NRS), female sex, and non-breast cancer predicted greater increase in CIPN (p < 0.05). Male participants responded better to the exercise intervention than female participants (p = 0.028)

Intervention group participants increased their mean daily steps by 649 (0.32 mi) to a mean of 4,820 steps per day, and the control group participants decreased in daily steps to 4,285 steps per day. The intervention participants’ steps per day were significantly higher than the control group’s at six weeks (p = 0.019). Intervention participants performed significantly more days of resistance band exercise (~ 3.5 days per week) than controls (p < 0.001).

This study provides preliminary evidence, suggesting that progressive light/moderate-intensity walking (prescribed based on step counts) and elastic band resistance training daily may reduce CIPN progression during the first six weeks of neurotoxic chemotherapy treatment.

• Risk of bias (no blinding)
• Risk of bias (sample characteristics)
• Unintended interventions or applicable interventions not described that would influence results
• Selective outcomes reporting
• Measurement/methods not well described
• Measurement validity/reliability questionable
• Subject withdrawals ≥ 10%  
• Other limitations/explanation: Secondary analysis originally aimed to evaluate effects of exercise intervention on physical activity, fatigue, cognitive impairment, and inflammation in 619 patients receiving chemothearpy. Although the 0-10 NRS is a gold-standard measure of pain, its one-item validity and reliability in measuring CIPN is questionable. No control/stratification for comorbidities that could influence CIPN, such as diabetes and the type and cumulative dose of neurotoxic chemotherapy received. Participants who withdrew from the study were older, and had greater fatigue and a lower education level at baseline (all p ≤ 0.019). More participants in exercise group withdrew compared to control group participants (p = 0.01). Questionable interpretation of the results; the authors frequently described the results as significant when the p was > 0.05 (their two-tailed significance α).

Light/moderate-intensity aerobic and strength training exercise is safe and may be beneficial for reducing CIPN in individuals receiving chemotherapy treatment; however, further research is needed to rigorously test the effect of various dosages of specific types of exercise on CIPN and evaluate the most feasible interventions that result in maximum adherence.