To synthesize the literature on the safety and efficacy of exercise training during and after cancer treatment and provide guidelines for exercise for patients with and survivors of cancer. Adults with cancer during and after adjuvant cancer treatment were addressed. The guidelines state that the focus is on sites where the most evidence exists:  breast, prostate, colon, hematologic, and gynecologic cancers.

Evaluation of evidence was based on categories from the National Heart, Lung and Blood Institute (A–D levels). Panel member reviews were presented and discussed at the roundtable, and guidelines were developed by consensus. Specific strategy and terms were not described. Guidelines were developed by an expert roundtable in which members were asked to review relevant literature. The guidelines were limited to an adult population and provided an overview of a volume of evidence in multiple outcome areas related to exercise.

A comprehensive and detailed set of guidelines for exercise approaches applicable for survivors of  breast, prostate, colon, hematologic, and gynecologic cancers was provided in the guidelines, as well as some of the issues of exercise training timing related to phases of care. The guidelines also provided a summary of evidence used per cancer site and identified gaps in research because of the small number of studies in some cases and small sample sizes in many of the studies.

Recommendations for exercise testing were as follows:

• Evaluate for peripheral neuropathies, musculoskeletal morbidities, and fracture risk in those who have received hormonal therapies.
• Assess for risks associated with bone metastases and cardiac risks.
• In patients with breast cancer, evaluate arm and shoulder morbidity prior to upper-body exercise.
• In patients with prostate cancer, evaluate muscle strength and wasting.
• In patients with colon cancer, check for infection prevention behaviors for existing ostomy.
• In patients with gynecologic cancers, evaluate for lower-extremity lymphedema prior to vigorous aerobics or resistance; in patients with morbid obesity assess for safety.
• Exercise testing before walking, flexibility, or resistance training is not required.
• In survivors with or at risk for lymphedema, one repetition maximum testing is safe.

Recommendations for exercise prescription were as follows:

• Allow adequate healing time after surgery (may be as much as eight weeks).
• Resolve arm or shoulder problems with patients with breast cancer before upper-body training.
• Swelling or inflammation in gynecology cases should be resolved before exercise training. 
• Patients with ostomies should have doctor permission before contact sports and weight training.
• Changes in symptoms are reasons to stop an exercise program.
• Patients with bone metastases may need to alter exercise intensity, duration, and mode because of fracture risk.
• Specific cancer site–related recommendations are provided for injury prevention and emergencies.

General activity guidelines were as follows:

• Avoid inactivity.
• Aerobic exercise recommendations are the same as general age-appropriate national guidelines.
• Resistance training should be supervised for at least 16 sessions for patients with breast cancer.
• Patients with radical prostatectomy should also perform a pelvic floor exercise with resistance training.
• Resistance training is more important than aerobics for patients who have received transplants.
• Resistance training should be used with caution in patients with lower-limb lymphedema.
• Age-appropriate flexibility training should be followed.
• Ostomies require avoidance of excessive intra-abdominal pressure.
• Research gaps and recommendations were outlined for yoga, sports, Pilates, and other exercises.
   

No participant associations were described.

The guidelines concluded that there was consistent evidence that exercise is safe during and after cancer treatment, with consideration of specific risks that are associated with various types. Exercise training can be expected to improve aerobic fitness, muscular strength, quality of life, and fatigue. Resistance training can be performed safely in patients with and at risk for lymphedema with breast cancer. Some exercise is recommended for all types of patients. Further study is needed in the areas of dose-response effects of exercise training. The guidelines provided additional evidence-based and expert support for the incorporation of various types of exercise in the care of patients with cancer during and after adjuvant treatment. Continued research is needed in this area in terms of research in other cancer types and determination of dose-response relationships for various outcomes.
 

To evaluate the onset of lymphedema after a one-year weight-lifting intervention versus no exercise among breast cancer survivors at risk for lymphedema

Patients were randomized to the weight-lifting intervention group or control group, who were to have no change in level of exercise. The weight-lifting intervention included a gym membership and 13 weeks supervised instruction with a remaining 9 months unsupervised. Specific equipment varied but provided upper-body exercises (i.e., seated row, supine dumbbell press, lateral or front raises, bicep curls, triceps pushdowns) and lower-body exercises (i.e., leg press, back extension, leg extension, and leg curl), 3 sets of 10 repetitions. Weights were increased for each exercise by the smallest possible increment after two sessions of completing 3 sets of 10 reps with no change in arm symptoms. Trainers called patients who missed more than one session per week. Those who missed two consecutive sessions were asked to reduce resistance and rebuild per protocol. All participants in the intervention or control group who developed lymphedema were given a custom compression garment and were required to wear garments during weight-lifting sessions. Certified fitness professionals employed by the centers received a three-day training course regarding exercise protocol and overview of lymphedema prevention, symptoms, and treatment.

• The study sample (N = 134) was comprised of female patients who had a diagnosis of unilateral nonmetastatic breast cancer one to five years prior.
• Mean age of participants was 54–56 years.
• Patients were included in the study if they
  • Had a body mass index of less than or equal to 50
  • No medical conditions limiting exercise
  • No weight lifting in year prior to study
  • No plans for surgery or absence for a month during the study
  • A stable weight
  • Were not trying to lose weight
  • No prior lymphedema diagnosis
  • No evidence of current lymphedema.

The study took place across multiple community fitness centers in Philadelphia, PA.

The study has clinical applicability for late effects and survivorship.

The study used a randomized controlled equivalence trial design.

• Patients self-reported demographics and treatment history.
• Surgical pathology reports were used to study removed lymph nodes.
• Weight and height (baseline only) were recorded.
• Whole-body dual-energy x-ray absorptiometry scan measured bone mineral density to avoid misrepresenting changes in relative fat mass because of changes in bone density.
• Physical activity outside of weight lifting was assessed using the International Physical Activity Questionnaire.
• Diet was assessed using the Diet History Questionnaire
• Water volume displacement measured lymphedema.
• Clinical laboratory technicians at Penn Therapy used standardized clinical evaluation based on Common Toxicity Criteria version 3.0.
• Participants were sent for evaluation of change for symptoms lasting one week or longer by fitness trainers or if three-month interval measurements by measurement staff indicated a change in treatment-arm volume of at least 5% inter-limb difference.
• Strength was measured at baseline and 12 months based on the maximum amount of weight patients could lift at once.
• Intervention adherence was evaluated by attendance logs kept by fitness trainers.
• Statistical analysis was performed using the Statistical Analysis System (SAS) version 9.2.
   

Women in the weight-lifting group became stronger with lower percentage body fat compared with the no exercise group. Lymphedema onset (5% or more increase in inter-limb volume difference during the 12 months) was 17% (n = 13) in the control group and 11% (n = 8) in the weight-lifting group.

The findings demonstrates that slowly progressive weight lifting will not increase the risk of lymphedema in breast cancer survivors, the primary objective of testing the safety of the weight-lifting intervention. 

• Key sample group differences could influence results.
• Replication to other fitness settings was limited by availability of instructors.
• Patients had limited access to clinical laboratory technicians for immediate evaluation and treatment.
• Garments to be provided to patients was not covered by insurance.

Additional research is needed to determine if weight lifting prevents lymphedema. Nurses should use caution in stating that exercise does not increase onset of lymphedema based on just this study, as it was conducted in a controlled environment, with careful instruction and observation of correct use of equipment and evaluation of arm symptoms and volume changes.

The database searched was MEDLINE through February 2005 to identify intervention studies designed to increase physical activity in adults. Only those studies with a concurrent comparison group with results presented separately for treatment and comparison groups were included.

The quality of 32 studies was assessed using prespecified criteria for internal validity. Twenty-two of 32 studies were rated as being of high methodologic quality and were retained for qualitative and quantitative analysis. The outcomes of physical activity interventions in patients receiving active treatment were analyzed separately from the studies of physical activity after treatment was concluded.

Outcomes were fatigue, health-related quality of life, symptom distress, immune function, hematocrit, body composition, physical exercise capacity (maximal oxygen consumption), and other physical performance measures.

Treatment evaluated aerobic physical activity of moderate to vigorous intensity three to five times per week for 20 to 30 minutes per session. The majority of the interventions lasted between five weeks and three months, with no follow-up at the end of the intervention. The majority of the studies used a control group in which no physical activity or other treatment was prescribed, although a few studies provided an intervention for the comparison group.

• Average sample size for the intervention group was 28 participants.
• The most common diagnosis included in the studies was breast cancer.
• The majority of the studies focused on the time period during or immediately following active cancer therapy. No study focused on palliation.

Although a consistent positive effect of physical activity on fatigue was noted using qualitative study review techniques, effect size calculations revealed no effect of physical activity on fatigue during treatment (weighted mean effect size = 0.13; 95% confidence interval [CI] [-0.06, 0.33]; p = 0.18) or after treatment (weighted mean effect size = 0.16; 95% CI [-0.23, 0.54]; p = 0.43) or on vigor/vitality during treatment (weighted mean effect size = 0.43; 95% CI [-0.07, 0.94]; p = 0.09). A large positive effect of exercise on vigor/vitality posttreatment was noted (weighted mean effect size = 0.82; 95% CI [0.05, 1.6]; p = 0.04). When fatigue and vigor/vitality were combined into one category (under the assumption that fatigue and vitality are the same attribute) and all studies were combined across treatment timing, the weighted mean effect size was still small (weighted mean effect size = 0.19; p = 0.03).

The results supported the conclusion that physical activity has a large positive effect on vigor/vitality after treatment is complete. There is some support from qualitative analysis of a consistent effect of physical activity on fatigue, although the magnitude of this effect may be too small to be clinically meaningful. The study findings also supported a preliminary conclusion that physical activity is generally well tolerated during and after cancer treatment, although the available literature does not allow conclusions to be drawn regarding adverse events from participation.

• The reviewed studies used small, self-selected samples.
• The reviewed studies were heterogeneous in terms of the outcome measures and interventions.
• The reviewed studies had gaps in the level of detail reported about individual study procedures and results.

To evaluate the efficacy of aprepitant plus a standard antiemetic regimen (granisetron plus dexamethasone) in preventing CINV for patients with multiple myeloma receiving high-dose chemotherapy and autologous stem-cell transplantation (ASCT)

Patients randomly were assigned to receive either aprepitant (125 mg orally on day 1 and 80 mg orally on days 2–4) plus granisetron (2 mg orally on days 1–4) and dexamethasone (4 mg orally on day 1 and 2 mg orally on days 2–3) or a placebo plus granisetron (2 mg orally on days 1–4) and dexamethasone (8 mg orally on day 1 and 4 mg orally on days 2–3). High-dose chemotherapy (melphalan 100 mg/m²) was administered on days 1–2, and ASCTs were performed on day 4.

• N = 362
• MEAN AGE = 58.1 years
• MALES: 230 (64%), FEMALES: 132 (36%)
• KEY DISEASE CHARACTERISTICS: Multiple myeloma
• OTHER KEY SAMPLE CHARACTERISTICS: High-dose chemotherapy; receiving ASCT

• SITE: Single site    
• SETTING TYPE: Inpatient  
• LOCATION: Large university hospital in Germany

• PHASE OF CARE: Active antitumor treatment

Prospective, placebo-controlled, randomized, double-blinded, parallel-group, single-center study

• Functional Living Index–Emesis (FLI-E) questionnaire to record quality of life
• Daily diary with a 100 mm Visual Analog Scale (VAS) to record episodes and severity of nausea and vomiting

Patients receiving aprepitant plus standard antiemetic therapy were significantly more likely to achieve complete response (no emesis and no rescue therapy within 120 hours of melphalan administration) (p = 0.0042), were significantly more likely to be without major nausea (p = 0.026) and emesis (p = 0.0036) within 120 hours of melphalan administration, and had a higher quality of life (p < 0.001) compared to the placebo plus standard antiemetic therapy group.

The addition of aprepitant to standard antiemetic therapy resulted in significantly less CINV and a positive effect on quality of life.

The addition of aprepitant to standard antiemetic therapy not only reduced CINV but also improved quality of life for patients receiving ASCT.

IV palifermin 60 mcg/kg per day was given for three consecutive days before chemotherapy cycle A2 or B2 and then for three consecutive days after chemotherapy. All patients received granulocyte colony-stimulating factor (G-CSF). Prophylactic treatment consisted of a number of agents, including tetracaine, chamomile, oral hygiene, and amphotericin B suspensions. Authors used previous studies as historical controls.

This study used a retrospective series of 10 patients with B cell acute lymphocytic leukemia (ALL) or aggressive B cell lymphoma. Patients had World Health Organization (WHO) Oral Mucositis grades of 3 or 4 during cycle A1 or B1 of high-dose methotrexate (HDMTX).

Patients were selected retrospectively from September 2004 to March 2007.

• WHO mucositis grading was obtained daily.
• Opioid use was recorded.

• Sixteen episodes of grade 4 and one episode of grade 3 mucositis were observed without palifermin.
• One episode of grade 4, four episodes of grade 3, and four episodes of grade 2 mucositis were observed with palifermin (p < 0.05).
• IV opioids were reduced from 2,403 mg to 640 mg morphine (p < 0.05).
• Duration of higher grade mucositis was reduced slightly from 12.9 days to 11 days (not significant).

• The sample size was very small.
• Historical controls were used.
• Other prophylactic measures may have had effects.
• No discussion of cost was provided.

To study the safety and effectiveness of training with a mechanical arm crank on lymphedema development after axillary node dissection

Patients were randomized to usual care or supervised training sessions with an arm crank. The training group had exercises for strength and endurance for 60 minutes twice weekly for 12 weeks. The training involved either passive motorized training, motor supported self-training, or training by patient-generated power alone. The training modality used depended on patient performance. Study outcome measures were obtained before and after study-related training.

• N = 49   
• MEAN AGE = 57
• FEMALES: 100%
• CURRENT TREATMENT: Not applicable
• KEY DISEASE CHARACTERISTICS: Breast cancer. All underwent axillary node dissection, and the majority had postoperative radiotherapy.

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

PHASE OF CARE: Late effects and survivorship

Randomized, controlled trial

• Body mass index
• Bioelectric impedance analysis (BIA)
• Arm circumference measurement
• Muscular strength—isometric capacity testing for latissimus dorsi and pectoralis muscles 
• European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-20 (EORTC QLQ C-30)
• Borg scale for effort during training sessions

An increase in lean body mass was observed in patients in the training group (p = 0.017) and decrease in body fat (p = 0.009). Muscular strength increased in both groups. No significant differences existed between groups in arm volume changes. Both groups showed a significant reduction in arm volume from baseline to the end of the study (p < 0.01).

No increase in lymphedema volume was reported with the training provided with the arm crank. This training did not improve lymphedema management compared to usual care.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• No description of usual care

The findings showed no increase in lymphedema with arm training using a mechanical training device. The use of this device appeared to be safe but was no more effective for arm volume reduction than whatever was provided as usual care.

STUDY PURPOSE: To assess the effects and tolerability of buprenorphine for cancer-related pain in adults and children

• FINAL NUMBER STUDIES INCLUDED = 19 
• TOTAL PATIENTS INCLUDED IN REVIEW = 1,421
• SAMPLE RANGE ACROSS STUDIES: 10–189 patients
• KEY SAMPLE CHARACTERISTICS: Not provided

APPLICATIONS: Palliative care

Five studies looked at sublingual buprenorphine versus another formulation, tramadol (one), or pentazocine (two). Pain ratings did not differ significantly from those for tramadol. Buprenorphine was associated with better pain relief than pentazocine. Transdermal buprenorphine was compared to a placebo, controlled-release morphine, or transdermal fentanyl. Pain scores did not differ significantly from fentanyl and were lower in comparison to controlled-release morphine. Intramuscular, epidural, or IV buprenorphine was not substantially different in pain reduction compared to morphine given via the same routes.

Although buprenorphine evidence was limited and of low quality, the findings of this analysis suggested that buprenorphine was an effective pain reliever. The evidence was insufficient to suggest buprenorphine as a first-line treatment choice.

• Low quality studies
• Very few studies with the same comparisons for evaluation
• Very little evidence in children

Buprenorphine appeared to be an effective analgesic for cancer-related pain although the limited evidence for various formulations and comparisons suggested that it was not the most appropriate choice for first-line treatment. Buprenorphine may be useful in patients who receive opioid switching, or for whom alternatives to standard analgesic choices are needed.

To evaluate the effect of gentle strength training on endurance and psychological outcomes in patients with breast cancer.

Patients were randomized to the intervention or control study groups. Patients in the control group participated weekly in gymnastic exercises, such as chair or floor exercises with various sports equipment. Those in the intervention group were trained with strength endurance training, according to individualized training plans based on a training load of 50% of one repetition maximum on a weekly basis. Both groups continued the weekly training program for six months. Data were collected at baseline, after three months, and after six months.

• Thirty-three participants (100% female) were included. 
• Mean age was 56 years.
• All participants had breast cancer and had completed initial antitumor treatments. 
• Participants were an average of approximately nine months since diagnosis.

• Single site 
• Other setting
• Germany

Patients were undergoing the transition phase after active treatment.

This was a randomized, two-group prospective study.

• Endurance test using a bicycle ergometer
• European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-BR-23) module for quality of life (QOL) and fatigue
• Body mass index (BMI)

There was a significant reduction in BMI in both groups. QOL and fatigue scores showed a significant improvement in both groups at three and six months (p < 0.01). There were no significant differences between groups. The pattern of fatigue change showed decline in both groups by three months. At the six-month time point, the intervention group continued to experience a decline, whereas those in the control group showed increased fatigue, although this level was still below that at baseline.

Both conventional gymnastic exercise and gentle strength training were associated with weight reduction and improvement in fatigue and QOL in women with breast cancer.

• The study had a small sample size, with less than 100 participants.    
• Baseline sample/group differences were of import.
• The study had risks of bias due to no control group and no blinding.
• Measurement validity/reliability was questionable.*
• * Baseline QOL measures were higher in the intervention group.  There was no information provided regarding patient adherence to weekly sessions.  Fatigue was only measured with a single item from the instrument used.  It was not clear whether patients had relevant levels of fatigue at baseline or if all exercise was supervised or if individuals performed the sessions on their own.

Findings suggested that both types of exercise were beneficial to patients with breast cancer.  Further research in this area would be beneficial to determine those types of exercise and the timing of exercise related to cancer treatment that are most effective for the prevention and management of fatigue.

To evaluate the effects of a 12-week resistance training intervention in patients with breast cancer during adjuvant chemotherapy

Patients were randomly assigned to the intervention or attention control group. The control group received a supervised group muscle relaxation program with the same session schedule as the intervention group. The exercise intervention involved the use of eight different machine-based progressive resistance exercises without an aerobic component. Both interventions were provided in group settings for 60 minutes twice weekly. Study measures were obtained at baseline and at the end of the intervention period.

• N = 95
• MEAN AGE = 52.7 years (range = 30–71 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: All participants had breast cancer. The majority of participants had stage 1 or 2 disease. The mean number of days since surgery was 56. All participants were receiving adjuvant chemotherapy.
• OTHER KEY SAMPLE CHARACTERISTICS: 18% had baseline depression 

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

• PHASE OF CARE: Active antitumor treatment

Randomized, controlled trial

• Fatigue Assessment Questionnaire (FAQ)
• European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
• Center for Epidemiologic Studies (CES-D) for depression
• Trail Making Test (TMT)

The overall between-group difference in fatigue was –5.8. This difference was not statistically significant. There was no overall effect of the intervention on the affective or cognitive dimensions in the fatigue measure. In a subgroup analysis of women who were not depressed at baseline, the between-group difference was –8.1 (p = –0.039). Fatigue increased in the relaxation group. Cognitive performance on the TMT improved in the exercise group compared to the control group, but the difference was not significant. Depression remained unchanged in both groups.

The findings of this study show that resistance exercise can be helpful in reducing fatigue during adjuvant chemotherapy, particularly in patients who have depressive symptoms. There were no apparent effects of the resistance exercise program on fatigue or cognitive function.

• Small sample (< 100)
• Risk of bias (no blinding)
• Key sample group differences that could influence results
• Other limitations/explanation: A significantly larger proportion of patients in the exercise group had higher depression scores at baseline (p = 0.0098). This difference may have affected overall findings.

Findings showed that resistance exercise reduced fatigue during adjuvant chemotherapy. These effects were more pronounced in women who did not have depressive symptoms at baseline. This points to the potential influence of depression on fatigue and the efficacy of interventions for fatigue. These results suggest the need to ensure the effective management of depressive symptoms to manage fatigue during treatment. The interventions studied here did not show an effect on depression or cognitive function.

To assess the effects of oral B vitamin complex for the prevention of chemotherapy-induced peripheral neuropathy (CIPN)

Patients newly diagnosed with cancer who were to receive oxaliplatin, taxanes, or vincristine were randomly assigned to receive B complex vitamins or placebo. The intervention was begun about one week prior to the first cycle of chemotherapy and continued for 12 weeks after chemotherapy was completed. Vitamins or placebo were taken twice daily with or after meals. Evaluations were conducted at baseline, after chemotherapy (two to four weeks), and at 12 weeks after completion of chemotherapy.

• N = 50 at three months, 15 at nine months   
• MEDIAN AGE = 53.81 years (experimental), 55.18 years (control)
• AGE RANGE = 29–75 years
• MALES: 33.3%, FEMALES: 66.7%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Varied tumor types; breast and lymphoma were most common.
• OTHER KEY SAMPLE CHARACTERISTICS: Taxanes were the most frequent treatment in the sample.

• SITE: Single site   
• SETTING TYPE: Not specified    
• LOCATION: Australia

PHASE OF CARE: Active antitumor treatment

Placebo-controlled, blinded, randomized, controlled trial

• Brief Pain Inventory (BPI)
• European Organization for Research and Treatment in Cancer Quality of Life Questionnaire (EORTC QLQ) 
• Patient Neurotoxicity Questionnaire (PNQ)
• Blood assays for B vitamins
• Total neuropathy score (TNS)

No significant differences existed between groups in total neuropathy scores at any time. Significant differences existed between groups in PNQ results at baseline (for motor) and at 12, 24, and 36 weeks for sensory items (p < 0.05). Blood tests showed that B vitamin supplementation increased levels of thiamine, pyridoxine, cobalamin, and folate compared to placebo.

This study did not provide clear evidence regarding the potential role of B vitamin supplementation for the prevention of chemotherapy-induced neuroxicity.

• Small sample (< 100)
• Measurement validity/reliability questionable
• Subject withdrawals ≥ 10%  
• Assessment tools for CIPN have questionable validity and clinical utility.
• The study was underpowered.

The aim of this study was to assess the prophylactic use of B vitamin supplementation; however, the study sample was insufficient to provide a valid assessment.