Exercise

STUDY PURPOSE: To evaluate current research evidence for exercise protocols effect on CIPN symptoms, balance control, physical function, and QOL

TYPE OF STUDY: Systematic review (no meta-analysis conducted)

DATABASES USED: Medline, Scopus, Bandolier, PEDpro, and Web of Science

YEARS INCLUDED: (Overall for all databases) This was not specified

INCLUSION CRITERIA: Studies that had physical exercise intervention and QOL or a balance evaluation, structured exercise protocol for patients with cancer with CIPN was preferable, English peer-reviewed and indexed manuscripts, comparisons of pre-/postintervention of cancer diagnosis, one or both genders, and all races/ages. 

EXCLUSION CRITERIA: Cross-sectional studies, case reports, published abstracts, dissertation materials, conference presentations

TOTAL REFERENCES RETRIEVED: N = 2221

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Literature search was clearly outlined but did not use standardized methodology (i.e., PRISMA); two reviewers independently examined abstracts, full manuscripts analyzed for eligibility and independently used the modified Cochrane Collaboration Back Review Group checklist to evaluate quality of studies on nine criteria and strength of evidence; high quality was determined if study met at least 5 out of 9 criteria, low quality was less than 5 out of 9; final quality score discussed between both reviewers for final determination of quality score, third researcher consulted for any discrepancies; extraction of data based on categorization for this study outcomes: CIPN symptoms, static balance control, dynamic balance control and quality of life and physical function

FINAL NUMBER STUDIES INCLUDED: N (studies) = 5 (2 of 5 were randomized studies, of high quality, three non-randomized and low quality) 

TOTAL PATIENTS INCLUDED IN REVIEW: 147 (25 dropouts) (n = 122)

SAMPLE RANGE ACROSS STUDIES: 14-56 years

KEY SAMPLE CHARACTERISTICS: All participants with a diagnosis of malignancy; all had peripheral neuropathy before starting the intervention; age range = 44-71.82 years (one study of older adults, four studies of mid adult); 84 females and 63 males; 131 participants were undergoing chemotherapy out of 147 before dropouts. In three studies, 100% of participants were actively undergoing chemotherapy; in two studies, 54% of participants were undergoing chemotherapy. Three studies evaluated CIPN supervised training intervention and two studies evaluated home-based intervention. Exercise types included aerobic walking/cycling, strength/elastic band training, calisthenics, core stability, sensory motor, and specific balance training alone or in combination. Exercise dosages ranged from 30 to 60 minutes per sessions, two to five times per week, for 3 to 36 weeks.

PHASE OF CARE: Multiple phases of care

APPLICATIONS: Elder care; palliative care

Three of four studies showed some modest improvement in CIPN with exercise; some small improvements found with exercise for static balance in all four studies; dynamic balance control evaluated in two studies, only one showed improvement with exercise; three of four studies showed improvements in QOL.

This systematic review of a small sample of five studies showed varying exercise interventions, with differing dose and duration of therapy, enhanced QOL and improved balance. However, this evidence synthesis is scant and drawing conclusions for practice would be premature as the majority of studies are of low quality. This systematic review highlights that more research is needed to determine specific exercise interventions targeted to specific cancer populations to understand the full benefit of exercise as an intervention strategy to reduce CIPN symptoms and related quality-of-life issues.

• Limited search
• Limited number of studies included
• Mostly low-quality/high-risk-of-bias studies
• High heterogeneity
• Low sample sizes

Other: poor choice and limited list of key terms in search strategy; literature search strategy and inclusion criteria did not specify year of studies, CIPN symptom outcome was not an inclusion criteria; study design and methodologies differed, control conditions of studies not adequately explained; different exercise interventions and time frames, different instruments across studies for outcome measures, including CIPN six, static/dynamic balance control, and QOL, some data does not fully represent the construct/categorization of study outcome measures. One study measured fear of falling substituting this as a QOL measure; one study did not measure QOL at all, one study did not evaluate CIPN symptoms as an outcome; cancer diagnoses/stage and type or number of chemotherapy regimens not specified; no effect sizes reported; only one study using intent to treat analysis; no data extraction or study reporting of adverse events of exercise interventions; selection bias in three of five studies

Exercise is a promising strategy in the management of CIPN; however, it is an understudied intervention. Large multi-center RCTs are needed to investigate specific types, doses and duration of exercise interventions tailored to specific cancer populations for CIPN, and related QOL outcome measures to identify best practices that can improve CIPN and related QOL needs.

• FINAL NUMBER STUDIES INCLUDED = 13
• TOTAL PATIENTS INCLUDED IN REVIEW = 590
• KEY SAMPLE CHARACTERISTICS: The majority of the studies were of patients with diabetic neuropathy (7 of 13 were exclusively diabetic neuropathy; 8 of 13 were randomized, controlled trials; and 5 of 13 were quasiexperimental).

PHASE OF CARE: Late effects and survivorship

The variety of interventions and outcome measures made the pooling of data in this literature review difficult. Overall, very few randomized, controlled trials exist in this field. The authors described single study results throughout the study but did not pool the results; rather, they placed them in table. Each study was evaluated separately.

Some evidence supports the use of exercise to improve function in those with peripheral neuropathy. Exercise can improve function, balance, and gait for individuals with polyneuropathies and may delay the onset of peripheral neuropathy when administered long-term. For maximum effect, exercises or interval training were to be performed for 2–3 sessions per week with a minimum of 100 minutes of activity. Some of the exercise regimens may not be feasible in patients with cancer because of other side effects of therapy.

Study inclusion was stated but not exclusion. Only 13 studied were evaluated. No pooled data existed—too much heterogeneity. The information may not be useful in oncology because the majority of studies were of patients with diabetes or autoimmune neuropathy.

Nurses should focus further research on exercise in chemotherapy-induced peripheral neuropathy and should educate patients on symptoms and possible interventions for this side effect.

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.

To determine the effectiveness of an aerobic and strength training program on neurotoxic symptoms, gait, balance, and quality of life in women with breast cancer treated with taxol

Women with breast cancer treated with taxol were randomized to either a strength/aerobic exercise program, which they performed at home, or to breast cancer education. The program was conducted for 12 weeks. Data were collected at baseline, every four weeks, and then three months postintervention. Education was provided to the control group, occurred at the same intervals as study group assessments, and lasted for 45 minutes. They also received reminder telephone calls every other week for data collection and equalized contact.

• N = 19  
• AGE = 48.8 years
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Patients newly diagnosed with stage I–IIIa breast cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Eight patients had a lumpectomy, six had a mastectomy, and five received neoadjuvant chemotherapy.

• SITE: Single site    
• SETTING TYPE: Outpatient  
• LOCATION: Oncology clinic in the Midwest

PHASE OF CARE: Active antitumor treatment

• Randomized, controlled trial

• Functional Assessment of Cancer Therapy (FACT)-Taxane
• Timed Up and Go Test
• Leisure-Time Exercise Questionnaire
• Symptom Experience Scale

No significant differences existed in results between the groups regarding neurotoxic symptoms, gait or balance, or quality of life. No significant differences existed between groups regarding stage of disease, level of exercise, age, taxol dose, or breast cancer symptoms.

The results indicated that patients randomized to the exercise group experienced a small but insignificant positive effect on neurotoxic symptoms, gait, and balance.

• Small sample (<  30)
• Risk of bias (no blinding)
• Findings not generalizable

Home exercise programs produced a small to moderate positive effect on gait and balance, symptoms, and quality of life. A large, randomized trial with patients receiving neurotoxic chemotherapy will help determine if this can be a positive intervention.

This study investigates the connection of providing an eight-week guided multimodal exercise class twice a week to patients with metastatic colorectal cancer in hopes of influencing their chemotherapy-induced peripheral neuropathy.

30 outpatients with metastatic colorectal cancer and with a history of chemotherapy treatment were recruited to participate in a randomized control trial. The intervention group participated in an eight-week supervised multimodal exercise class twice a week/60 min. This class included endurance, resistance, and balance training. The control group was given written recommendations to complete physical activity. Chemotherapy-induced peripheral neuropathy was measured using the FACT/COC-NTX questionnaire. Endurance capacity, strength, and balance were also measured at three separate intervals: before, after, and four weeks post-study.

• N: 30  (24 completed the study) 
• AGE: The mean age of the intervention group was 68.53 years. The mean age of the control group was 70 years (NS)
• MALES: 21 (70%) 
• FEMALES: 9 (30%) 
• CURRENT TREATMENT: Chemotherapy, other
• KEY DISEASE CHARACTERISTICS: Metastatic colorectal cancer

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: Germany

• PHASE OF CARE: Multiple phases of care
• APPLICATIONS: Palliative care

Randomized control trial

• FACT/GOG-NTX questionnaire for chemotherapy-induced peripheral neuropathy
• 6MWT for endurance measurement
• H1RM for strength measurement
• GGT-Rehab for balance measure

The study showed significant improvement in neuropathic symptoms in the intervention group compared to worsening symptoms in the control group (p = 0.023). Increase of balance was noted between groups (p = 0.048) along with static balance (TOI, p = 0.022; NXT, p = 0.006). The intervention group noted an increase in strength from baseline: bench press (p = 0.006), leg press (p = 0.002), and lat pull down (p < 0.001)

The implementation of a multimodal, supervised exercise program showed significance in counteracting the neuropathic symptoms related to chemotherapy, increasing muscle strength and increasing balance in patients with metastatic colorectal cancer.

• Small sample (< 30)
• Subject withdrawals ≥ 10%
• Other limitations/explanation: Unclear which exercise modality is responsible for the positive results.

Patients at risk for chemotherapy-induced peripheral neuropathy (CINP) could benefit from a supervised multimodality exercise class to counteract the worsening effects of CINP. Providing your patients with written instruction for exercise might not be enough of an intervention to combat the worsening of this side effect.