Databases searched were the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, CINAHL, British Nursing Index, AMED, SIGLE, and Dissertation Abstracts International through July 2007.

Twenty-eight published randomized, controlled trials investigating the effect of exercise on cancer-related fatigue in adults were identified.

Outcomes

Fatigue was assessed using various self-report measures, including the Functional Assessment of Cancer Therapy-Fatigue (FACT-F), fatigue subscale of the POMS, the Piper Fatigue Scale, and the Brief Fatigue Inventory (BFI). Only three studies incorporated more than one fatigue outcome measure.

Treatment Evaluated

Mode, intensity, and timing of exercise differed across studies. Thirteen studies investigated home-based/unsupervised exercise programs, whereas 16 studies investigated supervised, institutionally-based exercise programs. Some studies investigating supervised exercise programs encouraged participants to undertake additional home-based exercise. The mode of aerobic exercise included walking, stationary cycling, or a range of modalities. Three studies included strength training as a component of the exercise program, and two studies investigated the outcomes of resistance training in isolation. Two studies included flexibility training as a component of the exercise program, although several studies incorporated routine stretching as part of the warm-up, cool-down, or both. Yoga was investigated in two trials and seated exercise in one. The intensity of exercise varied greatly across studies, with the comparison complicated by differences in the methods (e.g., heart rate monitoring, predicted oxygen uptake, and patient perceived effort) used to monitor intensity in each study. The length of the intervention also varied greatly, ranging from three to 32 weeks; the largest proportion of studies had an exercise intervention duration of 12 weeks.

• There were 2,083 participants. 
• Participants had various cancer diagnoses, although the majority of studies investigated breast cancer only.
• Nineteen of the 28 studies investigated participants with a specific cancer diagnosis and nine investigated participants with a range of diagnoses.
• The time since diagnosis and stage of treatment (active versus posttreatment) varied widely between studies and, in some cases, within studies.

Using posttest means and mean change scores from the pre- posttests, exercise was found to be statistically significantly more effective than the control intervention in the management of fatigue. In separate analyses, dividing studies based on whether the intervention was performed during or following cancer treatment, exercise was consistently statistically significantly found to be more effective for fatigue than the control intervention. Similarly, positive results concerning the effects of exercise for fatigue were also found when only those studies performed in women with breast cancer were examined. Quantitative comparison of fatigue intervention outcomes in other disease-specific groupings was not possible due to limitations in the available data. However, two studies of the effects of exercise on fatigue in prostate cancer populations reported mixed results. A four-week, home-based walking program had no significant effect on fatigue, whereas a 12-week supervised resistance training program produced a statistically significant improvement in the exercise group compared to the control group. No statistically significant improvements in fatigue were observed in patients with colorectal cancer who were prescribed a 16-week, home-based cardiovascular and flexibility program; in patients with lymphoma attending a weekly supervised yoga session; or in patients with multiple myeloma receiving an individualized 32-week, home-based strength and aerobic training program.  Follow-up assessment of long-term outcomes was limited, with 18 of 28 studies failing to assess outcomes beyond the end of the intervention period. From the remaining ten studies that included a follow-up assessment, three did not present the follow-up data in the original publication.

Methodologic quality of the studies was modest (the majority of the studies assigned an Oxford Quality Score of 2 or 3 on the 0–5 scale, with higher scores indicating better methodologic quality).

• All studies lost points in the scoring of methodologic quality due to the failure of the design to conceal group allocation of study participants to the exercise intervention.
• The authors also noted that observer blinding was rarely reported in the included studies.
• Several studies had methodologic flaws, such as providing incomplete descriptions of dropouts or inadequate descriptions of the methods of randomization.
• Although 20 of the 28 studies provided some data on adherence to the exercise interventions, methods for reporting adherence varied between studies, making it difficult to control for adherence when comparing results across studies.

To evaluate the effects of yoga on quality of life, anxiety, depression, and sleep in patients with colorectal cancer.

• N = 44  
• MEAN AGE = 68.26 years (range = 40-87)
• MALES: 61.1%, FEMALES: 38.9%
• KEY DISEASE CHARACTERISTICS: All had colorectal cancer and were an average of 23 months since surgery
• OTHER KEY SAMPLE CHARACTERISTICS: The majority of patients were retired and were married

• SITE: Multi-site  
• SETTING TYPE: Outpatient    
• LOCATION: Germany

• PHASE OF CARE: Late effects and survivorship

• Randomized, controlled trial

• Functional Assessment of Cancer Therapy (FACT) colorectal and fatigue scales
• Hospital Anxiety and Depression Scale (HADS)
• Pittsburgh Sleep Quality Index (PSQI)

At week 10, the yoga group had greater decline in anxiety (p = 0.043) and depression (p = 0.038) scores, but, at week 22, there was no difference between groups. At week 10, there were no differences between groups in PSQI scores, however, at week 22, those in the yoga group had better sleep quality (p = 0.043). There was no relationship between home practice time and outcomes. Only about half attended yoga sessions, and average home practice was about one hour per week. There were no significant differences between groups in overall quality of life scores.

Yoga may be helpful to some patients to reduce sleep disturbances.

• Small sample (less than 100)
• Baseline sample/group differences of import
• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Measurement validity/reliability questionable
• Subject withdrawals of 10% or greater 
• Other limitations/explanation: More than 20% were lost to follow up. Baseline anxiety and depression scores were very low, so it is not likely that reduction would be seen due to floor effects, and those reductions seen have questionable clinical relevance.

These results did not show meaningful impact of yoga on anxiety or depression. Yoga was beneficial in terms of improving sleep, although changes seen were small, and findings are limited due to study limitations. Further research in the potential role of yoga for sleep improvement is needed.

To evaluate the effects of a 12-week traditional Hatha yoga and meditation intervention on menopausal symptoms in survivors of breast cancer

• N = 40  
• MEAN AGE: 49.2 years (SD = 5.9 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: The study included survivors of breast cancer with no metastatic tumors after completing antineoplastic treatment, surgical chemotherapy, or radiotherapy. Women were aged 30-65 years, with or without antiestrogen medications.
• OTHER KEY SAMPLE CHARACTERISTICS: Patients scored 5 points or more, moderate score, on the Menopause Rating Scale (MRS). Antiestrogens, nonhormonal, and antidepressant medication were included if dose was fixed/stabilized and no changes in perspective were noted in 24 weeks.

• SITE: Single site    
• SETTING TYPE: Not specified    
• LOCATION: Department of Gynecology Certified Breast Cancer at Malteser Hospital St. Anna, Duisburg, Germany

• PHASE OF CARE: Transition phase after active treatment

Unicenter, open-labeled, randomized clinical trial with two groups: (a) the group with yoga and meditation intervention and (b) the control group with usual care

• Menopause Rating Scale (MRS)
• Quality of life was measured with Functional Assessment of Cancer Therapy-Breast (FACT-B)
• Fatigue measured with Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F)
• Depression and anxiety were measured with Hospital Anxiety and Depression Scale (HADS)

Primary outcome: At week 12 and week 24, total menopausal symptoms were lower in the yoga group than in the usual care group (week 12: p = 0.004; week 24: p = 0.023). Regarding quality of life, significant group differences were observed at week 12 for the FACT-B total score (p = 0.002), and for the social (p = 0.024), emotional (p = 0.005), and functional well-being subscales (p = 0.024). There were no group differences for anxiety or depression. Women who received antiestrogen medication (n = 36) presented total menopausal symptoms lower in yoga group at week 12 (p = 0.013) but not at week 24 (p = 0.084). At week 24, no group differences were observed for any of the MRS subscales in the subgroup analysis (p = 0.075–0.352).

Yoga combined with meditation appears to be an effective intervention to relieve menopausal symptoms in survivors of breast cancer for at least three months after the end of the active neoplastic treatments. It can help reduce fatigue, and, for women who are receiving antiestrogen medication, yoga can have at least short-lasting effects.

• Small sample (less than 100)
• Risk of bias (no blinding)
• Risk of bias (sample characteristics)
• Unintended interventions or applicable interventions not described that would influence results 
• Key sample group differences that could influence results
• Intervention expensive, impractical, or training needs
• Groups can be different, as well as anxiety and depression scores at the beginning. Groups also can be contaminated one to another if there is contact.
• Previous experience in yoga was not controlled, and interventions are supposed to be adapted to the individual, so there can be differences in interventions for group members.
• It is unclear if there were individual or group yoga sessions.

Yoga is a good recommendation for patients with breast cancer to manage menopausal symptoms and to decrease fatigue. Intervention is effective to improve quality of life. Yoga does not have serious adverse events, and minor adverse events could be related to other causes.

STUDY PURPOSE: To assess the evidence for effects of yoga on quality of life and psychological health in patients with breast cancer and survivors

TYPE OF STUDY:  Meta analysis and systematic review

DATABASES USED: Medline, PsycINFO, EMBASE, CAMBASE, and Cochrane Library through 2/2012

KEYWORDS: Yoga, quality of life, mental health, psychological health, anxiety, depressive disorder, stress, distress, and terms for breast cancer

INCLUSION CRITERIA: Randomized controlled trial (RCT) of patients older than 18 with history of breast cancer; assess health-related quality of life (QOL) or well-being; mental, physical, function, social, or spiritual well-being; and/or psychological health

EXCLUSION CRITERIA: Studies that included yoga as part of a larger intervention, such as mindfulness-based stress-reduction, were excluded.

TOTAL REFERENCES RETRIEVED = 156

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used, and study quality was evaluated using Cochrane risk of bias criteria.

• FINAL NUMBER STUDIES INCLUDED: N = 12
• TOTAL PATIENTS INCLUDED IN REVIEW: N = 742

PHASE OF CARE: Multiple phases of care

Program length and intensity varied from daily interventions for one week to interventions weekly for six months. Four studies included an attention-control condition. Risk of bias was generally high. Meta-analysis showed moderate short-term effects of yoga on global health-related QOL (SMD = 0.62, p = .04). Large short-term effects were found for anxiety (SMD = -1.51, p < .01), depression (SMD = -1.59, p < .01), and distress (SMD = -0.86, p < .01). None of these effects were maintained at long-term follow-up. There was significant heterogeneity in analysis of all outcomes except for overall mental, social, and spiritual well-being. Analysis showed that significant overall effects were only seen among studies involving yoga during active anticancer treatment.

Yoga may have short-term benefit for patients for overall QOL, anxiety, depression, and general distress; however, these effects do not appear to be maintained. It appears that benefit may be mainly seen during the active treatment phase of care.

• Small overall number of studies that could be included in various meta-analyses
• High risk of bias in studies
• High heterogeneity
• Highly varied interventions
• Samples limited to patients with breast cancer

Participation in activities such as yoga during treatment may help patients with anxiety, distress, and depression and overall quality of life during active treatment. The optimum frequency and duration of this type of intervention is unclear, and variability and study limitations make showing strong support of this intervention difficult. Yoga has been shown to be safe for patients with cancer; thus, for those patients who are interested in participating in yoga, there does not appear to be any reason to avoid it. Further well-designed research in this area is warranted to continue to explore the most effective timing, duration, and approaches for yoga interventions.

STUDY PURPOSE: To evaluate the effects of exercise on patients with colorectal cancer

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 5 studies, 2 in meta-analysis 
• TOTAL PATIENTS INCLUDED IN REVIEW = 238
• SAMPLE RANGE ACROSS STUDIES: 18–102
• KEY SAMPLE CHARACTERISTICS: All had colorectal cancer.

PHASE OF CARE: Not specified or not applicable

Meta-analysis of three studies showed no significant overall effect of exercise on fatigue or quality of life. Exercise was associated with improved physical fitness (p = 0.0006).

Exercise was shown to be effective in improving physical fitness; however, physical fitness did not have a significant effect on fatigue in patients with colorectal cancer in this study.

• Limited number of studies included
• High heterogeneity
• Low sample sizes

Exercise has been shown to improve fatigue in multiple patient groups. This review was limited by the small number of studies limiting samples to patients with colorectal cancer.

Evaluate the current literature on antidepressant effects of exercise in cancer survivors. Also to explore potential moderating variables related to participant, cancer and exercise characteristics.

TYPE OF STUDY Combined systematic review and meta analysis

DATABASES Medline, Medline in Process, Psycinfo, Embase, CINAHL, Cochrane database, Cochrane central register of controlled trials, Allied and Complementary Medicine, Biosis Previews, Sports Discus
   

KEYWORDS  terms related to cancer, exercise, and depression    

INCLUSION CRITERIA Studies were eligible if they were a RCT of adults with cancer, compared exercise program with usual care, exercise program was chronic in nature (at least 4 weeks), reported depression pre and post  intervention, used depression inventory or clinician interview to define depression symptom, English language

EXCLUSION CRITERIA studies that used quality of life or moods scales to measure depression
Study Aims Evaluate the current literature on antidepressant effects of exercise in cancer survivors. Also to explore potential moderating variables related to participant, cancer and exercise characteristics.  
 

TOTAL REFERENCES RETRIEVED : N =60

METHOD OF STUDY EVALUATION AND COMMENTS ON LITERATURE USED Two investigators independently reviewed articles with discrepancies resolved by consensus.

All studies included aerobic exercise with some also including strength training. Exercise programs were implemented prior to or during treatment in 47% of the studies. Interventions varied from unsupervised home based to supervised facility based with frew having mixed supervision. Intervention length ranged mostly from 4-14 weeks, with the longest being 52 weeks.  
 

FINAL NUMBER STUDIES INCLUDED: N = 14 articles describing 15 RCTS   TOTAL SAMPLE SIZE: N =  1371   SAMPLE RANGE ACROSS STUDIES : 18-209, including exercise and control groups combined

KEY SAMPLE CHARACTERISTICS 60% (9) studies included breast cancer survivors. The average age was 51.6 years. 76.9 of those who reported race/ethnicity were Caucasian. Of those reporting cancer stage, 75% were patients with non-metastatic disease.

PHASE OF CARE Active Treatment

APPLICATIONS Late Effects and Survivorship

Effect size of -.22(p=0.04) was found comparing exercise group to control groups. Home based exercise had increased depressive symptoms (effect size(ES)e 0.16) compared to exercise location and facilities, laboratories, gyms (ES= -0.45, -0.77, -.014). Supervised exercise had the greatest effect (ES=-0.67) compared to mixed supervision (ES=-0.32) and unsupervised activity showed a small increase in depression (ES=0.25). Duration of greater than 30 minutes had a larger effect (ES=-.57) compared to less than or equal to 30 minutes (ES=0.01)

Overall, exercise had a small to moderate impact on depression symptoms which varied based on location of exercise, supervision, and duration. 

Exercise at places where patients interact with others had a greater effect size associated with reduction of depression symptoms. It would be important to recognize this when intervening with exercise. Future research should measure the significance of social interaction during exercise and depression symptoms.  Also, more work is necessary to understand if the exercise intervention improves QOL.

STUDY PURPOSE: To synthesize the available literature to determine the role of honey in reducing oral mucositis, time to onset of mucositis, weight loss, and treatment interruptions among patients with head and neck cancers undergoing radiation with or without concomitant chemotherapy

TYPE OF STUDY: Meta analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 5 for meta-analysis and 8 for systematic review 
• TOTAL PATIENTS INCLUDED IN REVIEW = 244 (according to the authors)
• SAMPLE RANGE ACROSS STUDIES: Author did not report each sample size, but some numbers were found in the report and a figure. According to the figure, each study had 20–33 participants per group, and it was assumed that each study had approximately 40–60 participants. However, one study used in systematic review seemed to have 131 patients in the study. Sample sizes were not reported well in this study. 
• KEY SAMPLE CHARACTERISTICS: The authors included only randomized controlled trials with a honey intervention for patients with head and neck cancer who were receiving radiation therapy. The authors took appropriate screening procedures to select articles that met the criteria. This shrunk the sample size but resulted in more reliable results for meta-analysis.

PHASE OF CARE: Active antitumor treatment

Honey was significantly better in lowering the risk for treatment interruptions and probably less weight loss but did not decrease the rate of the peak mucositis score. The results for prolonged onset of mucositis is favorable with the honey intervention in two studies, but one study did not show a significant difference.

• Limited number of studies included
• No quality evaluation
• High heterogeneity
• Low sample sizes

The results showed that the honey intervention is effective in reducing treatment interruption. Other measures (weight loss, peak mucositis score, time to mucositis) need further meta-analysis to establish. Further well-designed research is needed to confirm the usefulness of honey preparations.

To evaluate the effectiveness of Scrambler therapy on cancer pain, chemotherapy-induced peripheral neuropathy, neuropathic pain, and quality of life

Scrambler therapy is cutaneous electrostimulation that blocks the effect of pain information on the cutaneous nerves. In this study, all participants received the intervention to the affected area for 45 minutes daily for 10 consecutive days (Monday–Friday). Pain was measured before and after each intervention session.

• N = 39  
• MEAN AGE = 56.5 years
• MALES: 41%, FEMALES: 59%
• KEY DISEASE CHARACTERISTICS: The majority of the study participants had chemotherapy-induced peripheral neuropathy (n = 33), followed by post-mastectomy pain (n = 3), postherpetic neuralgia (n = 2), and radiation-related pain (n = 1).
• OTHER KEY SAMPLE CHARACTERISTICS: Participants had to have pain or symptoms of peripheral neuropathy for longer than one month with an average daily pain rating of greater than 5 out of 10, or numbness that bothered the participant at least “a little bit.” Additionally, participants had to be adults with a life expectancy of longer than three months and an Eastern Cooperative Oncology Group performance status score of 0–2.

• Setting was not described.

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

• A repeated measures design with no control group was used to evaluate the intervention.

• Numerical Rating Scale (0–10) for pain
• Brief Pain Inventory (questions 2–5 and 9)
• Eastern Cooperative Oncology Group Chemotherapy-Induced Peripheral Neuropathy 20 scale
• All measurements were performed pre- and post-intervention.
• Comparisons were made between baseline day 1 and days 14, 30, 60, and 90.

Improvement in pain was found at all secondary endpoints (days 14, 30, 60, 90), with a statistically significant difference in pain between baseline and day 30 (p = 0.0049) and change over time (p = 0.0002). Sensory and motor components of the chemotherapy-induced peripheral neuropathy scale also were found to improve with statistically significant sensory improvement between baseline and day 30 (adjusted p = 0.0007) and change over time (p < 0.0001). For the motor component, significant findings included improvement between baseline and days 14, 30, and 60 (adjusted p = 0.0143, 0.1035, 0.0094, respectively) and change over time (p = 0.0019). Improvements in all components of the Brief Pain Inventory were found (i.e., “interference with normal life,” which were maintained for mood, sleep, relationships, etc). Pain interference with walking was improved significantly between baseline and day 30 (p = 0.0003). Use of opioids did not change.

Scrambler therapy improved acute and chronic pain among patients with cancer. Additionally, it had a lasting effect three months post-treatment. Quality of life also was improved with this pain treatment. Further study is needed to determine generalizability of these findings to other patients with cancer.

• Small sample (less than 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Risk of bias (no appropriate attentional control condition)
• Unintended interventions or applicable interventions not described that would influence results
• Findings not generalizable
• Intervention expensive, impractical, or training needs
• Other limitations/explanation: What opioids and dose the participants were taking during the study, who delivered the intervention, and the expense of the intervention or training needs were unclear. Additionally, findings are not generalizable to other patients with cancer because of the lack of a control group or attentional control condition and the small, heterogeneous sample.
• Questionable protocol fidelity

Scrambler therapy appears to be a promising intervention for cancer-related pain and has no adverse effects. Because who delivers this treatment and its expense are unclear from this article, the implications to nursing are unclear. However, nurses knowing about this treatment is important because it may become a common method for treating cancer-related pain in the future.

To test the theory:  \"Inhaled opioids usually are ineffective with report of respiratory depression; however, fentanyl may be more readily absorbed with less bronchospasm and thus relieve dyspnea.\"

Patients were given 25 mcg of fentanyl with 2 mL of saline via a nebulizer.

• The sample was comprised of 35 patients (20 women, 15 men) with terminal cancer who reported shortness of breath. 
• Average age was 56 years.
• Thirty-four patients were on oxygen. 

• Inpatient
• Oncology unit

The study used a convenience sample, uncontrolled design.

• Patients’ perceptions of breathing (same, worse, or improved) were measured one hour after treatment.
• Respiratory rate and oxygen saturation were measured at baseline and at 5 and 60 minutes following the intervention.

• Twenty-six of 32 patients (81%) reported improvement in breathing.
• Three of 32 (9%) patients were unsure of their results.
• Three of 32 (9%) patients reported no improvement.
• Mean oxygen saturation significantly improved from 94.6% to 96.8% (p < 0.001) at five minutes and to 96.7% (p < 0.006) at 60 minutes.
• Mean respiratory rate significantly decreased from 28.4 at baseline to 25.8 at five minutes (p < 0.03) and to 24.1 at 60 minutes (p < 0.02).

Fentanyl improved all three measures and may offer substantial relief of dyspnea. No significant side effects were reported.

• The study was not randomized and needs confirmation in a randomized, controlled trial.
• The impact of the carrier saline is unknown.
• Also unknown is the cause of attrition of three patients and whether patients were opioid tolerant or naïve.

Clinical questions about repeated dosing and method of administration (mask or mouthpiece) remain.

To examine the effectiveness of the use of a controlled-release transdermal patch preparation of mecamylamine (AG1004)

Patients who had received at least one cycle of chemotherapy and experienced grade 1 or 2 diarrhea were randomized to receive transdermal mecamylamine (AG1004) 4 mg every 24 hours or placebo using an identical-looking patch. The patch was applied 24 hours prior to chemotherapy and reapplied daily for the duration of the treatment cycle. Patients were allowed to use loperamide, codeine phosphate, or octreotide on a rescue basis for any active episodes of diarrhea. During the next cycle, the AG1004 dose was increased to 8 mg per day. Evaluation was done at the end of the first day of each cycle and at the end of the overall cycle of chemotherapy. Daily logs were used to record bowel movements and use of rescue medication.

• The study reported on 64 patients.
• Mean age was 61.2 years with a range of 35–88 years.
• The sample was 25% male and 75% female.
• Patients had various tumor types, with colon and breast cancer most common.
• All patients were receiving chemotherapy that has been associated with diarrhea, and all had experienced diarrhea in a previous cycle.
• Patients were being treated with fluorouracil (5-FU), capecitabine, or irinotecan.

This was a multisite, outpatient study conducted in the United Kingdom and Romania.

• All patients were undergoing the active treatment phase of care.
• This study has clinical applicability for elder care.

This was a double-blind, randomized, placebo-controlled study.

• The Bristol stool scale and the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) grading were used.
• Patients kept daily diaries of bowel movements and use of rescue medication.

• Overall compliance with treatment was an average of 90% in both study groups.
• Overall response (OR) was 1.26 in favor of the treatment, based on physician assessment, but this was not statistically significant.
• Based on patient reporting of four or fewer bowel movements per day from diaries, more patients were classified as responders in the treatment group (OR = 6.4, 95% confidence interval [CI] = 1.7–24.6, p = 0.05). 
• Use of rescue medication was low in both groups. 
• Overall use of loperamide was less in the treatment arm at both treatment dosages, with a greater trend observed with the 8-mg dose level (p = 0.05).
• No differences were found between groups in other associated gastrointestinal symptoms.

AG1004 was associated with less diarrhea compared to placebo on day one of chemotherapy cycles and did not appear to have significant adverse effects. AG1004 may be helpful in preventing chemotherapy-induced diarrhea.

The sample size was small with fewer than 100 participants.

This study demonstrated some promising results, suggesting that treatment with AG1004 may be useful in preventing chemotherapy-induced diarrhea in patients being treated for cancer with agents known to be associated with diarrhea. Further research is warranted to confirm these findings.