The 15-week, multidimensional rehabilitation program included aerobic bicycle training plus general muscle force training, supervised sports sessions, psychoeducational sessions, and informational classes.

• The sample was comprised of 72 patients (85% female) who were posttreatment.
• Mean age was 51.4 years (standard deviation = 9.6 years).
• Of the patients, 61% were women with breast cancer.
• Patients were included if they
  • Were 18 years or older
  • Had their last cancer treatment greater than three months previously
  • Had an estimated life expectancy of one year or greater 
  • Had an indication for rehabilitation.

• Outpatient
• Center for Rehabilitation in The Netherlands

The study used a pre-/posttest design with measures before and after completion of the program. No control group was used.

• Multidimensional Fatigue Inventory (MFI)
• Rotterdam Symptom Checklist (RSCL)
• Exercise capacity and muscle force
• Short Form 36 Health Survey (SF-36)

• Of the patients, 77.8% completed the program and were posttest drop-outs.
• Drop-outs had more recurrences.
• There was significant improvement in every dimension of the MFI.
• The greatest effect was on physical fatigue.
• Effect sizes ranged from –0.35 to –0.78.
• There were no differences based on time since treatment.

• The intervention was delivered by an interdisciplinary team, including physical therapists and a psychosocial specialist.
• The role of nursing is unclear and atheoretical.
• Consequences were used as predictors.
• There was no control for overlap in the tools.
• It is not possible to determine which aspects of the intervention were effective.

The study measured the efficacy and side effects of treatment with salvia officinalis for hot flashes in men with prostate cancer treated with androgen deprivation.

Salvia officinalis extract was provided in 150 mg tablets to be taken 3 times daily.  Thujone was confirmed to be absent from the product.  Patients were to complete a hot flash diary daily.  Patients were seen in clinic every 1-2 weeks for 10 weeks at which time they turned in diaries, received a new supply of the salvia tablets, and had a clinical examination and bloodwork.

Nine men, with a mean age of 68 years (range 62-73), were enrolled. All had prostate cancer, were receiving androgen deprivation therapy, and were experiencing hot flashes. Patients were excluded if they were unlikely to comply with the protocol or had an uncooperative attitude

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

PHASE OF CARE: Transition phase after active treatment

 This was a quasiexperimental feasibility study.

• Hot flash diary
• Moyad hot flash scale (rates as mild, mod or severe according to experience) calculated as total score
• Hot-flash related daily interference scale (HFRDIS)
• Hormone levels
   

Salvia use reduced hot flashes from a pretreatment mean Moyad score of 112 to a posttreatment mean of 54 (p = .002).  There was a decrease in LH and FSH levels.  There were no significant effects on testosterone, blood pressure, or cholesterol levels.  Hot flash reduction appeared within the first 3 weeks.  After this time, Moyad scores were essentially stable.  Sub-group analysis of  8 patients who had at least grade 2 hot flashes at baseline showed a substantial variability of responses.  One patient developed a skin rash that may have been associated with the use of salvia

 Salvia officinalis was associated with reduction in hot flash scores and minimal side effects in this small pilot study.

• Small sample (< 30)
• Risk of bias (no control group) 
• Risk of bias (no blinding)  
• Risk of bias (no random assignment)
• Measurement validity/reliability questionable*
• Subject withdrawals ≥ 10%  
• Use of total Moyad hot flash scores per week has not been tested for validity or reliability.    
   

This study provides little information to support use of salvia officinalis for hot flashes in these patients.  The sample size is too small and study design insufficient to examine potential efficacy and the actual side effect profile of this intervention.  Larger, well-designed clinical trials are needed.

To determine the efficacy of a low bacterial diet (LBD) versus a control diet in preventing the occurrence of infection and reducing related mortality in patients with cancer receiving immunosuppressive chemotherapy.

Databases searched were the Cochrane Central Register (CENTRAL), DARE, PubMed, EMBASE, and CINAHL, as were conference proceedings from multiple professional groups.

Included in the study were patients with cancer receiving chemotherapy causing episodes of neutropenia, use of an LBD versus a control diet, with an LBD defined as any diet intended to reduce the ingestion of bacterial and fungal contaminants by exclusion of uncooked fruits and vegetables, cold cuts, undercooked eggs and meat, unsterilized water, unpasteurized milk products, and soft cheeses. The control diet was any other diet.

Children younger than 1 year were excluded from the study.
 

Six hundred nineteen total references were retrieved.

Risk of study bias was evaluated using the Cochrane Handbook for Systematic Reviews of Interventions.

• After exclusion, the final number of studies examined was three.
• The sample range across studies was 19 to 153.
• Samples included patients treated with remission induction chemotherapy for acute myeloid leukemia, high-risk myelodysplastic disease, or acute lymphoblastic leukemia.
• One study had a pediatric population.

• Patients were undergoing the active antitumor treatment phase of care.
• The study has clinical applicability for pediatrics.

Included studies had different definitions of infection rate and different outcomes measured and defined. Blinding and selection bias were problems in the study design, and only one study provided explicit data on the use of empirical antibiotics and antimycotics. Data could not be pooled for meta-analysis. In all three studies, there was no significant difference in outcomes between groups.

There is currently no strong evidence demonstrating the need or effectiveness of LBDs, and due to differing outcome measures, diets used and cointerventions for prophylaxis pooling of results was not possible. No firm conclusions can be drawn, and no recommendations for clinical practice are made.

• Small number of studies
• Various study design limitations and risks of study bias

The results suggest that no firm conclusions can be made about the usefulness of an LBD and that there is no strong evidence to show the effect. Additional well-designed research in this area would be helpful.

To determine the effect of a combined rehabilitation program (physical training [PT] and cognitive-behavioral training [CBT]) and PT alone on cancer-related fatigue (CRF) compared with a control group receiving no intervention.

Two groups of cancer survivors were randomly assigned to 12 weeks of PT or to 12 weeks of PT plus CBT. The control group was not randomized. PT included aerobic training combined with progressive resistance exercise (twice weekly for two hours). CBT included self-management skills based on problem-solving (once weekly for two hours). In the analysis, fatigue scores were also compared to a general Dutch population of similar age.

• The sample was comprised of 147 patients (44% male, 56% female).   
• Mean age was 46 years.
• Breast cancer was predominant in all three groups.
• Patients were cancer survivors one to two years posttreatment.

• Multisite  
• Four rehabilitation centers in The Netherlands

The study was a randomized, controlled trial.

Multidimensional Fatigue Inventory (MFI) was used preintervention (Cronbach α range 0.73–0.83) and postintervention (Cronbach α range 0.84–0.88) to measure five domains:  general fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue.

Levels of fatigue significantly decreased in all domains in all groups (p < 0.05; effect size across domains range –0.38 to –1.36), except in mental fatigue in the control group. No significant differences were found in decline of fatigue between the intervention groups. Patients completed 82.4% of PT and CBT sessions and 83.5% of PT sessions. In the post hoc analysis, patients with lower educational levels reported less decline in physical fatigue, reduced motivation, and reduced activation.

PT combined with CBT was equally effective in reducing fatigue, suggesting that CBT had no benefit beyond PT. Patients in the control group also showed a significant decline in fatigue, suggesting that time alone is also effective related to fatigue reduction.

• The study lacked an appropriate control group.
• There was an overrepresentation of patients with breast cancer.
• The study lacked a group receiving CBT only.
• The study duration was limited (12 weeks). 

The study supported the effectiveness of PT in the treatment of CRF.

To evaluate the effects of low and moderate to high intensity exercise on fatigue, fitness, and treatment completion rates

Patients were randomized to usual care control, low-intensity, or moderate- to high-intensity exercise groups. Those in the low-intensity group did home-based self-managed activity for at least 30 minutes for five days a week. Those in the moderate- to high-intensity group participated in 50 minute sessions two times per week and were encouraged to also be physically active for 30 minutes per day for five days per week. Study measures were obtained at baseline, at completion of chemotherapy, and six months later. Exercise programs began with initiation of chemotherapy and continued until three weeks after completion of chemotherapy.

• N = 197
• MEAN AGE = 50.7 (SD = 9.1)
• FEMALES:  100%
• KEY DISEASE CHARACTERISTICS:  Breast cancer;  the majority were stage II or III; 78% had radiation therapy as well as chemotherapy
• OTHER KEY SAMPLE CHARACTERISTICS: 70% were working full or part time

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

Randomized, controlled trial

• Fatigue Quality List
• Multidimensional Fatigue Inventory
• EORTC-QLQ –C30
• Hospital Anxiety and Depression Scale
• Sleep Quality Inventory
• Physical Activity Scale for the Elderly
• Grip strength with dynamometer
• Exercise diary
• Steep ramp test fitness and endurance testing

Participants attended 71% of exercise sessions, and 55% of those on the low-intensity program followed recommendations at least 75% of the time. Those in the moderate- to high-intensity group had the best endurance and muscle strength results at the end of chemotherapy. Those in the higher-intensity exercise group also had the lowest physical fatigue levels at the end of chemotherapy (p < 0.001).  Those in the low-intensity group had slightly lower fatigue levels than controls. There were no significant differences between groups at three months. There were no significant differences between groups in anxiety or depression scores.

Results of this study showed the lowest physical fatigue scores during chemotherapy among those participating in moderate- to high-intensity sessions. It is unclear if this difference between exercise groups was related to exercise intensity or the overall difference in the amount of exercise done. Effects on fatigue were not maintained at three months postchemotherapy and there were no effects on measures of anxiety or depression

• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)

This study adds to the already extensive body of evidence showing the benefits of exercise in managing fatigue during cancer treatment. It is unclear if the amount, duration, or intensity of exercise are most important for deriving benefit from exercise. Group differences seen at the end of chemotherapy were not maintained three months later, and it is unclear what amount of physical activity was done between the end of treatment and final study measurements.

STUDY PURPOSE: To investigate the effects of exercise on physical and psychosocial dimensions of fatigue during adjuvant treatment for breast cancer

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 5 
• TOTAL PATIENTS INCLUDED IN REVIEW = 714
• SAMPLE RANGE ACROSS STUDIES: 70–206
• KEY SAMPLE CHARACTERISTICS: All had breast cancer and were receiving adjuvant chemotherapy. In two trials, women were also receiving radiation therapy and/or hormonal therapy.

PHASE OF CARE: Active antitumor treatment

Analysis showed that exercise had significant benefit for general fatigue (ES = –0.22), physical fatigue (ES = –0.35), reduced activity (ES = –0.22), and reduced motivation (ES = –0.18) (p = 0.05) but no effect on cognitive or affective dimensions of fatigue. Five studies included resistance exercises. Two studies compared resistance and aerobic exercise.

Exercise was shown to have beneficial effects on the physical dimensions of fatigue with low to moderate effect sizes. No apparent effects on emotional and cognitive components of fatigue were observed.

Limited number of studies included

This analysis adds to the large body of evidence showing the beneficial effects of exercise on fatigue. In this study, only the physical aspects of fatigue were affected. Additional interventions may be needed to address the psychosocial dimensions of fatigue.

Adult patients with acute leukemia receiving remission-induction chemotherapy.
Patients received either antibacterial prophylaxis (AP) and low-microbial diet (LBD) or AP and normal hospital diet (NHD) to prevent infections.

Patients were randomized into two groups.

• Patients receiving antibiotic prophylaxis (AP) and low-bacterial diet (LBD)
• Patients receiving AP and normal hospital diet (NHD).  

AP included ciprofloxacin 500 mg every 12 hours and oral fluconazole 50 mg every 24 hours and was started before initiation of chemotherapy and discontinued when leukocyte counts recovered to 1,000/mm³ or higher.

• The total sample size was 20 (15 men and 5 women).
• All were patients with acute leukemia undergoing remission-induction chemotherapy.

Randomized, controlled pilot study

• Infection was measured by gastrointestinal tract colonization with yeast or gram-negative bacilli or fever higher than 38ºC.
• Stool was measured daily for bacterial colonization.  
• A Student's t test compared degree of colonization between the two groups. Differences at cycle-specific points in time were evaluated with a multivariate analysis of variance (MANOVA). Differences in temperature were measured by the Fisher’s exact test.

No statistically significant differences were found between the two groups for rates of infection.

• The small pilot study and sample size were inadequate to observe significant differences between the study groups.
• The study did not measure whether patients were adherent to their assigned diets.  
• Randomization could not create two equal groups.  
• Patients received AP.
• Results cannot be generalized because of the small sample size.

To update the American Society of Clinical Oncology Guidelines regarding the role of bone-modifying agents (BMAs) in the treatment of metastatic breast cancer

Databases searched were MEDLINE and the Cochrane Library to July 2009. Investigators performed a supplemental search of items published through November 2010. Studies selected were those in which patients were randomly assigned to receive a BMA or placebo or alternative intervention. Subjects had metastatic breast cancer. Recommendations were developed by consensus following review of the evidence.

The clinical guideline update made the recommendations that follow.

• BMAs are recommended for patients with metastatic breast cancer who show evidence of bone destruction.
• No specific BMA is recommended over another. Dosage recommendations for specific agents follow.
  • Denosumab: 120 mg subcutaneously every four weeks.
  • IV pamidronate: 90 mg over at least two hours every 3–4 weeks.
  • IV zoledronic acid: 4 mg over at least 15 minutes every 3-4 weeks.
• The guideline recommends dosage, intervals, and monitoring in patients with reduced creatinine clearance levels.
• All patients should have a dental examination and preventive dental care prior to using a BMA.
• The standard of care for pain and a BMA should be provided at the onset of cancer bone pain.
• BMAs are an adjunctive therapy for cancer-related bone pain, not a first-line pain management

Bone-modifying agents are recommended for patients with metastatic breast cancer who have evidence of bone destruction as an adjunct to standard pain management.

The study examined the effect of soy phytoestrogens on hot flashes in postmenopausal women with breast cancer:

The study randomized 157 participants with a mean age of 55 years and who had been previously treated for breast cancer from August 1998 to February 2000. Nine women (6%) became ineligible after randomization, and 25 (16%) dropped out because of time commitment (n = 9), intolerance of the study beverage (n = 10, 7 in the soy group, 3 in the placebo group), or other reasons (n = 6). The remaining 123 women completed the study by June 2000.

•  Inclusion criteria:
  • Women had completed treatment for breast cancer more than four months prior to enrollment (tamoxifen use was allowed), were menopausal (12 or more months of amenorrhea), and had not used HRT for 4 or more months, were experiencing troubling hot flashes, defined as a score (frequency × intensity) of 10 or more per week.
  • Women using complementary therapies and prescription medications, including tamoxifen, were eligible if no change in therapy for four months or longer.
  • All participants were instructed to avoid soy-based foods and soy supplements during the study.
• Exclusion criteria:
  • Based primarily on factors that modify estrogen or phytoestrogen metabolism or that had the potential to require medical intervention: smokers, using antibiotics, inflammatory bowel disease, liver impairment (gamma-glutamyl transferase and alkaline phosphatase of ≥ 1.5 times normal), or recurrent breast cancer.
  • Also, soy allergy or regular consumption of soy foods.

In this randomized, placebo-controlled, double-blind clinical trial, participants were stratified for tamoxifen use and randomized to a soy beverage (n = 59) containing 90 mg of isoflavones or to a placebo rice beverage (n= 64).

Women recorded the number/severity of hot flashes with a daily diary for 4 weeks at baseline, then for 12 weeks while consuming 500 ml of a soy or placebo beverage daily. The primary outcome variable was the mean 24-hour hot flash score, created by summing the hot flash score (frequency × intensity) during the day and night. The main analysis, with Student’s t test, was a comparison between groups in the change in the mean 24-hour hot flash score during the 4 weeks of baseline compared with the last 4 weeks of treatment. This analysis was also conducted for the hot flash number and score during the day and night and the hot flash number per 24 hours. Secondary analyses included a comparison between groups of:

1. Consumption and acceptability ratings for each beverage
2. Frequency of side effects
3. Responses to the study exit questionnaire
4. Serum isoflavone concentrations

The average serum isoflavone concentration of the soy beverage was also calculated. All statistical tests were two-tailed and used a significance level of alpha = 0.05.

This trial does not support the use of a soy beverage containing phytoestrogens as a treatment for hot flashes in breast cancer survivors. The soy beverage did not alleviate hot flashes in women with breast cancer any more than did a placebo. Mild gastrointestinal side effects were experienced by both groups but occurred with greater frequency and severity with soy.

STUDY PURPOSE: To summarize and analyze the evidence provided by randomized, controlled trials (RCTs) on physical exercise interventions among patients with cancer undergoing HSCT

TYPE OF STUDY: Systematic review and meta-analysis

TOTAL REFERENCES RETRIEVED: 232 originally retrieved; 180 excluded by title and abstract

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Cochrane collaborative tool for assessing for risk of bias used for bias; two of the authors scored articles. If a disagreement occurred, a third author reviewed.

• FINAL NUMBER STUDIES INCLUDED = 11 (14 articles met criteria; three were reports of the same study looking at different outcomes and, therefore, excluded) used in qualitative systematic review; three studies used in the meta-analysis; for outcome of fatigue, six studies examined effect of exercise on fatigue and two of these were included in meta-analysis
• TOTAL PATIENTS INCLUDED IN REVIEW = 734; for meta-analysis, 148; for fatigue meta-analysis, 115
• SAMPLE RANGE ACROSS STUDIES: 18–135 for total, 33–81 for meta-analysis, and 34–81 for fatigue meta-analysis
• KEY SAMPLE CHARACTERISTICS: Several countries; allogeneic or autologous HSCT; multiple myeloma, any type of leukemia or lymphoma. No other demographic data provided

• PHASE OF CARE: Active treatment, post HSCT; intervention initiated either during hospitalization or after discharge
• APPLICATIONS: Elder care

Only six of the studies examined the effect of exercise on fatigue. In meta-analysis of 115 patients (two studies), exercise significantly reduced fatigue at discharge (n = 115; SMD = 0.53; 95% CI [0.16, 0.91], p = .005). The meta-analysis indicated that training during hospitalization has a positive effect on fatigue in patients receiving an allogeneic HSCT.

Results of meta-analysis could not be confirmed through individual review of the other four studies, as only two showed statistically significant effect for fatigue in favor of the exercise group.

Physical functioning could not be evaluated by meta-analysis due to differences in study design and outcomes, but the majority of the studies did suggest a positive effect of exercise on functioning.

Exercise intervention during hospitalization can have a positive effect on fatigue at discharge for patients undergoing HSCT.

• Literature search limited to English
• Heterogeneity of type and timing of exercise intervention

Best outcomes were seen at discharge, suggesting that starting interventions before or just after transplantation are most effective. Further research into the optimal exercise program is needed.