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.

STUDY PURPOSE: To determine the effectiveness of administering antibiotics prior to long-term central venous catheter (CVC) insertion, or flushing to prevent catheter-related infections

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 11
• TOTAL PATIENTS INCLUDED IN REVIEW = 828
• SAMPLE RANGE ACROSS STUDIES: 27–108 patients
• KEY SAMPLE CHARACTERISTICS: Patients with varied tumor types

PHASE OF CARE: Not specified or not applicable
 
APPLICATIONS: Pediatrics

Five studies evaluated prophylactic antibiotic administration prior to CVC insertion, and six studies evaluated flush or catheter lock solutions. Pooled analysis of evidence comparing antibiotic and heparin solution to heparin only solution showed that the combination of antibiotic was associated with less catheter-related sepsis than the heparin only solution (468 participants, relative risk [RR] = 0.47, 95% confidence interval [CI] [0.28, 0.8], p = 0.0051). The majority of these instances were in children, and low heterogeneity existed among these studies. Five of the six studies used vancomycin in the flush mixture. No difference existed in the risk of catheter-related infections between those who did and did not receive prophylactic antibiotics prior to CVC insertion.

This review did not demonstrate a beneficial effect of prophylactic antibiotics prior to long-term CVCD insertion. The findings suggest that the use of antimicrobial catheter flush or lock solutions may be helpful for infection reduction from gram-positive organisms; however, the majority of studies used vancomycin, which has been not recommended for standard use.

• Low sample sizes
• Lack of specificity and consistency in outcomes

The use of catheter flush and lock solutions that contain a combination of antibiotics and heparin may help prevent or reduce catheter-related infection in patients with long-term tunneled central venous catheters.

To determine whether lactulose or polyethylene glycol (PEG) effectively promotes bowel function in critically ill patients, and to identify whether one is superior to the other.

On day 3 in critical care, consenting patients who had no bowel movements were randomized to one of three arms: lactulose, PEG 3350, or placebo. The lactulose solution was 13 gm of lactulose in 100 ml of sterile water. The PEG 3350 solution was 13.125 gm of PEG 3350 in 100 ml of sterile water. Finally, the placebo was 100 ml of sterile water. Each patient was medicated with the study liquid every eight hours via a nasogastric tube and was to receive 11 doses of treatment medication.

• The study reported on a sample of 308 critically ill intensive care unit (ICU) patients who did not have cancer.
• Mean patient age was 35.3 years (SD = 16.5) in the PEG group, 65.5 years (SD = 15) in the lactulose group, and 68.8 years (SD = 13.8) in the placebo group.
• The sample comprised 118 women and 190 men.

Two ICUs in the Netherlands

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

• Acute Physiology and Chronic Health Evaluation II (APACHE II) 
• Sepsis-related organ failure assessment score
• Daily abdominal x-ray in patients with severe abdominal tenderness, abdominal distention, or suspected ileus
• Medication assessment
• Stool record

• Lactulose and PEG were more effective than placebo (69% versus 74% versus 31%, p = 0.001).
• No difference was found in the effectiveness of lactulose versus PEG (p = 0.27).
• Lactulose reduced length of stay (LOS) in the ICU compared with PEG or placebo. In addition, patients with earlier bowel movements had shorter LOS.
• Morphine affected defecation, but PEG may be better in this patient group. Neither cisapride nor erythromycin appeared to affect defecation.
• Adverse drug events were acute intestinal pseudo-obstruction, perforated ulcer, acute abdomen, death, and sinus bradycardia.

Both lactulose and PEG promoted bowel movements equally. In patients receiving morphine, PEG had a more significant effect.

The study lacked a lead-in period or data on patients’ prior bowel function and history of constipation.

Bowel function is promoted with the use of either lactulose or PEG. Lactulose may reduce LOS, and PEG may be better for patients who also are receiving morphine, but additional study is needed.

To investigate the effect of intensive home-based nurse-provided education on pain levels, pain knowledge, quality of life, anxiety, and depression in patients with cancer

Patients with cancer were randomized to receive either a pain education intervention or usual care. Pain, knowledge, quality of life, anxiety, and depression were measured at baseline and after four and eight weeks. In the intervention group, effects on symptom levels were communicated to the treating physician. The program included a brochure about pain management, instructions about how to record pain intensity in a diary, and simulation of help-seeking behavior. In the intervention group, palliative care nurses made three home visits. After these visits, nurses communicated with the physician, by means of a written report of pain control and recommendations regarding dose or medication changes. Home visits were at weeks 1, 3, and 6. Follow-up telephone calls to members of the intervention group occurred at weeks 4 and 8.

• The sample was composed of 20 patients age 18 or older.
• In the intervention group, 52.1% of patients were male and 47.9% were female. In the control group, 38.3% of patients were male and 61.7% were female.
• All patients
  • Had been diagnosed with cancer and informed of their diagnosis.
  • Were able to understand and complete the questionnaire.
  • Had a present pain score of 4 or higher on a 0–10 scale.
  • Agreed to participate in the study.
• Patients were excluded from the study if they had completed their curative anticancer treatment before the year 2000.

• Multisite
• Home
• Limburg, the Netherlands

• Phase of care: not stated
• Clinical applications: elder care, palliative care

Randomized controlled trial

• Brief Pain Inventory (selected questions)
• Translated version of the Family Pain Questionnaire (Ferrell, Rhiner, & Rivera, 1999), to measure patients’ knowledge about pain
• European Organization for Research and Treatment quality of life questionnaire (EORTC QLQ-C30 version 3.0), to measure quality of life and nonpain symptoms
• Dutch version of the Hospital Anxiety and Depression Scale (HADS)

At four weeks, the level of pain had decreased in the intervention group (p = 0.02) but not at eight weeks. Significant decreases in pain only persisted in those patients with a high pain score (7–10) at baseline (p = 0.00). Knowledge of pain was significantly increased in the intervention group at week 8 (p < 0.00). Authors found no correlation between increased pain knowledge and decreased pain levels. In 60% of cases, recommendations in nurses' reports were ignored.

In the short term, the nurse-administered pain-related education program lowered pain intensity in patients with cancer and increased patients' knowledge about pain.

• The study had a risk of bias due to no appropriate attentional control condition.
• The patients in the study knew that they were enrolled in pain research.
• Study design did not account for differing severities of illness and disease progression.
• Written communication with the treating physicians proved inadequate.
• Authors provided no information about any changes made in pain management regimens during the course of the study.

In regard to pain and pain management, additional attention must be paid to patient education and to communication between patients and healthcare professionals. The following components should be characteristic of patient education programs: involvement of the patient and family or caregivers, communication with the patient to reinforce information and monitor the plan, integration of medical care into the nursing education program, clear instructions regarding provider notification, and use of a pain diary. The components have the potential to reduce pain. Study findings showed that communications to physicians, written by palliative care nurses, were ignored 60% of the time, suggesting that this form of communication is ineffective. Educating the patient and helping patients to self-advocate in interactions with physicians are important goals.