Effects of exercise during chemotherapy on chemotherapy-induced peripheral neuropathy: a multicenter, randomized controlled trial

Abstract

Purpose: Over half of all cancer patients receiving taxane-, platinum-, or vinca alkaloid-based chemotherapy experience chemotherapy-induced peripheral neuropathy (CIPN), which includes numbness, tingling, pain, cold sensitivity, and motor impairment in the hands and feet. CIPN is a dose-limiting toxicity, potentially increasing mortality. There are no FDA-approved drugs to treat CIPN, and behavioral interventions such as exercise are promising yet understudied. This secondary analysis of our nationwide phase III randomized controlled trial of exercise for fatigue examines (1) effects of exercise on CIPN symptoms, (2) factors that predict CIPN symptoms, and (3) factors that moderate effects of exercise on CIPN symptoms.

Methods: Cancer patients (N = 355, 56 ± 11 years, 93% female, 79% breast cancer) receiving taxane-, platinum-, or vinca alkaloid-based chemotherapy were randomized to chemotherapy or chemotherapy plus Exercise for Cancer Patients (EXCAP©®). EXCAP is a standardized, individualized, moderate-intensity, home-based, six-week progressive walking and resistance exercise program. Patients reported CIPN symptoms of numbness and tingling and hot/coldness in hands/feet (0-10 scales) pre- and post-intervention. We explored baseline neuropathy, sex, age, body mass index, cancer stage, and cancer type as possible factors associated with CIPN symptoms and exercise effectiveness.

Results: Exercise reduced CIPN symptoms of hot/coldness in hands/feet (-0.46 units, p = 0.045) and numbness and tingling (- 0.42 units, p = 0.061) compared to the control. Exercise reduced CIPN symptoms more for patients who were older (p = 0.086), male (p = 0.028), or had breast cancer (p = 0.076).

Conclusions: Exercise appears to reduce CIPN symptoms in patients receiving taxane-, platinum-, or vinca alkaloid-based chemotherapy. Clinicians should consider prescribing exercise for these patients.

Trial registration: Clinical Trials.gov , # NCT00924651, http://www.clinicaltrials.gov .

Keywords: CIPN; Exercise; Neuropathy.

Figure 1

CONSORT diagram of study participants.

Figure 2

Exercise reduces the severity of CIPN symptoms per patient-reported numbness and tingling (left; trend-level effect) and hot/coldness in hands/feet (right). Error bars show 95% confidence intervals from 170 exercise patients and 185 control patients. The p-values correspond to differences in exercise and control conditions from regression (Table 2).

Figure 3

Exercise works particularly well in reducing CIPN symptoms for older patients. CIPN symptoms were assessed using patient-reported numbness and tingling (top) and hot/coldness in hands/feet (bottom). Error bars show 95% confidence intervals from 108 patients in the youngest tertile (59 exercisers, 49 controls) and 109 patients in the oldest tertile (53 exercisers, 56 controls).