To determine if the use of a human epidermal growth factor (EGF)-based cream can prevent radiation dermatitis in patients with breast cancer treated with radiation

Patients with breast cancer needing post-operative radiation randomly were assigned to use human recombinant EGF-based cream (intervention) or general supportive skin care (control). The intervention group applied study cream three times daily to the radiated area from start of treatment through two weeks post-completion of treatment. The control group washed gently with or without mild soap, patting to dry. No cosmetics, perfumes, creams, or lotions were allowed on the treated area in the control arm.

• N = 40
• MEAN AGE: Intervention group: 57.3 years (40.2–74.0 years); control group: 51.8 years (36.5–76.1 years)
• MALES: 0%, FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Unilateral breast cancer, no skin invasion by tumor, breast-conserving surgery, presence or absence of adjuvant chemotherapy, radiation to minimum dose of 45 cGy without use of bolus
• OTHER KEY SAMPLE CHARACTERISTICS: No concurrent chemotherapy, rashes, or unhealed wounds in treatment area. No history of previous radiation therapy (RT) to chest wall, connective tissue disorder.

• SITE: Single site  
• SETTING TYPE: Not specified  
• LOCATION: Department of Radiation Oncology, Kyung Hee University Medical Center, Seoul, Republic of Korea

• PHASE OF CARE: Active antitumor treatment

• Single-blind, randomized preliminary study

Examination of site was completed prior to RT, weekly during RT, and six weeks post-RT. Skin changes were scored using the Radiation Therapy Oncology Group (RTOG) criteria by a radiation oncologist blinded to group assignment. Pain was evaluated with a 10-point visual analog scale. Intervention patients completed a questionnaire regarding ease of cream application at the end of the study.

Although there was a difference in the intervention and control groups in terms of grade 3 dermatitis, (15% compared to 40%), there was no statistical difference between the intervention of human recombinant EGF-based cream and the control of supportive skin care. As with previous studies, total RT dose and lymph node radiation were prognostic factors for grade 3 radiation dermatitis. This study did not look at patient-related prognostic factors that potentially contribute to increased radiation dermatitis.

• Small sample (< 100)
• Risk of bias (no blinding)
• Measurement validity/reliability questionable
• Other limitations/explanation: As with other studies, the RTOG skin toxicity scoring, although utilized by many practices and clinical trials, has not been tested for validity and reliability.

There continues to be no “best practice” for prevention and treatment of radiation dermatitis. Practice varies worldwide. Further studies with a large sample size and inclusion of a double-blinding would be useful for this product as several studies have shown with EGF for wound healing.

To evaluate chemotherapy-induced nausea and vomiting and adverse events when dexamethasone is eliminated on days 2 and 3 of moderately emetogenic chemotherapy (not including anthracyclines or cyclophosphamide) in combination with palonosetron or another 5HT3 receptor antagonist

The control group received 9.9 mg of dexamethasone IV then 0.75 mg of palonosetron IV before moderately emetogenic chemotherapy then either 8 mg of oral dexamethasone or 6.6 mg of IV dexamethasone on days 2 and 3 of chemotherapy. The treatment group received only 9.9 mg of dexamethasone IV then 0.75 mg of palonosetron IV before moderately emetogenic chemotherapy and no additional prophylactic antiemetics. Rescue antiemetic drugs (excluding dexamethasone, NK1 receptor antagonists, serotonin reuptake inhibitors, and serotonin–norepinephrine reuptake inhibitors) were allowed for both the treatment and control groups. 

• N = 305 (151 in treatment group and 154 in control group)  
• MEAN AGE = 64 years (range = 23–88 years)
• MALES: 173 (57%), FEMALES: 132 (43%)
• KEY DISEASE CHARACTERISTICS: Not specified (inclusion criteria was just malignant tumor)
• OTHER KEY SAMPLE CHARACTERISTICS: Received primarily oxaliplatin-based chemotherapy then irinotecan- and carboplatin-based chemotherapy in a one-day administration; 45% (n = 138) consumed alcohol within 180 days of chemotherapy

• SITE: Multi-site    
• SETTING TYPE: Not specified    
• LOCATION: Hokkaido, Japan

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Elder care  

Open-label, noninferiority, randomized, comparative, phase 3 study

• Gastrointestinal symptom diary of number of vomiting events and nausea rated on a four-point Likert scale that was completed by patient every 24 hours for five days after chemotherapy administration.
• Adverse events were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE), but no indication of how the data were gathered was given.
• The exacerbation of symptoms by one grade level or higher compared to baseline was considered an adverse event.
• Complete control and complete response rates in acute and delayed phases 

The noninferiority of the experimental group in regard to complete response rate (acute and delayed phases) and complete control rate (overall, acute, and delayed phases) was demonstrated. There was no difference between the treatment and control groups. A subgroup analysis according to age, sex, and chemotherapy showed no statistical differences in complete response rates. No significant difference in adverse events was found between the treatment and control group with primary events in both groups being constipation, hiccups, anorexia, and elevated alanine transaminase.

There was no difference in chemotherapy-induced nausea and vomiting (acute and delayed) or adverse events between one-day dexamethasone plus palonosetron versus three-day dexamethasone plus palonosetron among patients receiving moderately emetogenic chemotherapy (not including anthracyclines or cyclophosphamide).

• Measurement/methods not well described
• Measurement validity/reliability questionable

The one-day administration of dexamethasone (with palonosetron) was adequate in controlling acute and delayed nausea and vomiting in patients receiving moderately emetogenic chemotherapy when the chemotherapy did not include anthracyclines or cyclophosphamide.

Evaluate the effects of a self-help program on depression and anxiety in women with breast cancer receiving chemotherapy

Patients were assigned to intervention or treatment groups by authors (not random assignment). The intervention was a self-learning package aimed at rehearsing the chemotherapy procedure, improving beliefs in managing side effects, and helping build problem-solving skills. This group also was given a professional-led support group that met two to three times during the study. The control group received usual care including a chemotherapy education leaflet. Nurses monitored patient progress from review of patient diaries in the intervention group that documented side effects and self management performed at the beginning of each cycle of chemotherapy. Nurses involved with the intervention were educated and demonstrated increased knowledge regarding improving coping processes in daily living. Data were collected at baseline, one week, three months, and six months.

• N = 65      
• MEAN AGE: Intervention = 47.7 years (SD = 8 years), control = 49.5 years (SD = 10.9 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: All had breast cancer at stages 1–3. All had previous surgery.
• OTHER KEY SAMPLE CHARACTERISTICS: Most had breast-conserving surgery. The majority had less than a bachelor’s degree education level.

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

PHASE OF CARE: Active antitumor treatment

Non-random, two-group comparison, quasi-experimental—historical control approach

• Center for Epidemiological Studies Depression Scale (CESD)
• State-Trait Anxiety Inventory (STAI)
• SF-36
• National Cancer Institute-Common Toxicity Criteria version 2.0

No significant differences were found in outcomes between study groups. Study measures improved over time in all patients.

This study did not find that the intervention tested here had an effect on depression or anxiety.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Risk of bias (no appropriate attentional control condition)
• Questionable protocol fidelity
• No information is provided about patient compliance with diaries and symptoms experienced. No method was used for determining intervention fidelity. No information is provided as to patients' actual attendance at support group sessions. If patients in both groups were being treated in the same location, whether group contamination could have occurred is unclear. The control comparison used was actually a historic control. How the program was designed is unclear, and no apparent theoretical foundation of the program design exists. Although not statistically significant, baseline anxiety and depression scores were lower in the control group, which may have affected the ability to detect differences. Analysis was the comparison of average scores at each study time point, but changes in these scores were not analyzed. Changes in anxiety and depression scores appeared to be greater in the intervention group—analysis of differences in the size of the improvement may have shown different significance. Data reporting is questionable—confidence intervals reported with F values do not appear to be actually related to those values.

This particular study did not demonstrate effectiveness of the intervention tested here. The study had several limitations. Anxiety and depression improved in all patients, suggesting that usual nursing education provided was just as effective as the expanded approach used here. Several study results have suggested that interventions aimed at improving anxiety and depression are most effective for patients who have clinically relevant anxiety and depression.

To evaluate the effectiveness of dexamethasone and pyridoxine on the frequency and severity of palmar-plantar erythrodysesthesia (PPE) in patients with solid tumors receiving pegylated liposomal doxorubicin (PLD).

Evaluable patients had at least two cycles of therapy. A total of 51 cycles of PLD was applied to the 19 patients. The maximum tolerated dose was 60 mg/m² every 28 days. In a second step, interval reductions at the highest four weekly doses from 28 to 21 to 14 days were planned. Patients received oral dexamethasone 8 mg BID on days 1 to 5 with vitamin B6 100 mg BID continuously along with PLD.

• The study reported on a sample of 19 patients who had solid tumors and were receiving PLD.
• PLD doses ranged from 40 to 60 mg/m².

• Department of Medicine at the University of Tuebingen Medical Center in Germany
• Department of Medicine at the University of Essen Medical Center in Germany

PPE was evaluated with a scale from grade 1 to 4. The specific grading scale was not discussed.

• Three of seven patients with 21-day PLD intervals developed grade 3 or 4 PPE.
• At the 28-day PLD interval, grade 3 PPE occurred in only in 1 of 12 patients who were receiving 60 mg/m² PLD during the third cycle. That patient discontinued dexamethasone on day 2.

Compared to reported frequencies of up to 25%, the incidence of PPE caused by PLD appeared to decrease with concomitant dexamethasone and vitamin B6.

• The sample size was small.
• This was not a randomized clinical trial, and no control or comparison group was used.
• The description of the measurement tool or method used to grade PPE symptoms was inadequate, and reliability and validity were unclear.

• Databases searched were MEDLINE, CINAHL, and the Cochrane Library (December 2007–November 2010).
• Authors used the same search terms as Bennett, Bagnall, and Jose Closs (2008), whose publication said that details of the search were available upon request.
• Studies were included if they
  • Were randomized controlled trials or controlled trials in which the control group received usual care or attention only.
  • Included adults with pain from active cancer and not pain from cancer treatment.
  • Used a patient-based educational intervention on an individual basis.
  • Assessed pain-related outcomes. 
• Studies were excluded if they used psychobehavioral methods in the intervention.

• The final number of studies included was 34.
• The sample range across studies included a total of 4,139 patients in 24 interventions. The number of patients in the 11 statistically significant studies was 1,041. The range of sample size was 30–1,256 patients.
• The range of mean patient age was 48–77 years.
• Of all patients, 57% were women and 43% were men.
• Cancer diagnoses in the sample were primarily lung, breast, prostate, gastrointestinal, gynecologic, hematologic, and head and neck cancers.
• The majority of studies (14) were conducted in the United States.

• Structural components of the intervention included the factors that follow.
  • How the intervention was delivered.
  • What materials were given to patients.
  • Receiver and provider of the intervention.
  • Whether interactions took place between providers and receivers.
  • Level of individualization (structured or tailored) for each patient.
  • Contact time between clinicians and patients or family caregivers.
  • Timing of the intervention
• The 16 content components of the intervention were divided into four categories:
  • Cognition.
  • Behavioral.
  • Goal setting.
  • Direct contact between research staff and clinicians.
• Authors found no apparent patterns, for any single component or any combination of components, with statistically significant and clinically meaningful effects. This may be due to the lack of homogeneity in study designs and the variability of the structure and content components.
• Other factors may play a role in an intervention's efficacy (e.g., provider’s empathy, setting of the intervention).
• Spending more time with patients did not always result in increased knowledge or changes in patients’ behaviors. Similarly, multiple interventions did not always result in increased knowledge or behavior changes.
• Optimal dose and timing of the intervention to improve cancer pain management are unknown.

Although the efficacy of various intervention components could not be clearly delineated, this systematic review provides an overview of the various structural and content components of intervention studies to improve cancer pain management and an evaluation of combinations of components.

• One limitation was the fact that authors included published studies only.
• The number of studies included was small, which may have led to overestimation of effect sizes.

Nurses need to be aware of the various structural and content components of interventions to support patients’ self-management of cancer pain. The interventions should be culturally appropriate and include written material; a face-to-face educational session of at least 15 minutes; and information about pain treatment, cognitive barriers to pain management, and implementation of self-management pain strategies.

To evaluate the PRO-SELF^© Plus Pain Control Program in a German population to determine effect sizes and feasibility

Participants received six visits and four phone calls from an intervention nurse, who taught them effective ways to self-manage their pain, including how to set pain goals, how to titrate prescribed analgesics, how to communicate with their physician, and how to identify management strategies to achieve their pain goals. They also received nurse coaching on their recent successes and failures, as well as individualized information about their medications during each visit and phone call.

• N = 39
• AVERAGE AGE = 59.5 years
• MALES: 51%, FEMALES: 49%
• KEY DISEASE CHARACTERISTICS: Lung, breast, and other cancers; also evaluated fatigue, cognition, anxiety, and depression

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

• PHASE OF CARE: Active antitumor treatment

• Single-center, pilot, randomized, controlled trial

• Numerical Pain Rating Scale for primary outcome measures
• Patient pain questionnaire to evaluate patients’ knowledge of how to manage cancer pain
• For additional symptoms (e.g., fatigue, cognition, anxiety):
  • Hospital Anxiety and Depression Scale
  • German Memorial Symptom Assessment Scale
  • Fatigue assessment questionnaire
  • DemTect
  • Eastern Cooperative Oncology Group performance status
  • Self-efficacy questionnaire

Neither average nor worst pain scores demonstrated statistically significant group-by-time interaction effects between the intervention and control group over the 10-week or 22-week period. The difference in the knowledge scores between the intervention and control groups was statistically significant. A large percentage of participants did not complete the study for various reasons.

This study was the first to adapt a U.S.-developed pain intervention for a German audience. It did increase pain self-management knowledge and determine effect sizes for pain intensity scores.

• Small sample (less than 100)
• Subject withdrawals 10% or more

The nursing intervention piece of this trial can have a great effect on the participants. In the U.S. and German trials, the nursing interventions were able to have an effect on fear of addiction, fear of tolerance, physical dependence, and the patients' understanding of taking their medications on a schedule.

A group exercise training (GET) intervention was delivered in a structured format three times per week for 16 weeks. The one-hour GET training sessions emphasized physical activities that promote aerobic fitness, strength, and flexibility. The warm-up period lasted 10–15 minutes, the aerobic training phase lasted 20 minutes, and the resistance training and cool-down phase lasted 20 minutes. Exercise intensity and duration were prescribed on an individual basis using the results from baseline fitness assessments. Two exercise physiologists provided each session. Data were collected at baseline, week 8, and week 16.

• The study reported on a sample of 40 sedentary women, aged 45 or older, who had been diagnosed and surgically treated for stage I, II, or III breast cancer.
• Most women were within 12 months of diagnosis, and all were postsurgery.
• Most women were concurrently undergoing adjuvant therapies.

A quasi-experimental design was used.

• Beck Depression Inventory (BDI)
• State-Trait Anxiety Inventory (STAI)
• Positive and Negative Affect Schedule (PANAS)
• Hamilton Rating Scale for Depression (HRSD)
• Functional Assessment of Cancer Therapy (FACT)
• Cancer Rehabilitation Evaluation System (CARES)
• Global Assessment Scale (GAS)
• Life Functioning Scales (LFS)
• Physiologic measures
  • Heart rate and blood pressure, height and weight
  • Body fat through skinfold fat thickness
  • Single-stage submaximal treadmill walking test
  • Sit-and-Reach Test to measure flexibility
  • Variable resistance equipment to measure body strength

BDI, PANAS, and HRSD were significantly improved from baseline to week 16. There was no statistically significant change in anxiety, as measured by STAI, after the exercise intervention. At baseline, participants were not experiencing high levels of distress.

Anxiety levels were not changed significantly from this exercise program, although other health benefits were reported.

• The study had a small sample.
• Outcomes were conceptualized and measured multidimensionally rather than unidimensionally (e.g., aerobic capacity or mood/distress only).
• The sample included patients with breast cancer only.
• The study had special costs or training due to use of exercise physiologists.
• The study required individual tailoring of intervention.

To assess effectiveness of a once-a-day fentanyl patch for patients receiving a 72-hour patch that does not last for 72 hours

Patients identified as having end-of-dose failure with a 72-hour fentanyl patch were identified and converted to the once-a-day patch according to manufacturer recommendations. In the evening of the switch day, the new patch was applied immediately after removing the 72-hour patch. Treatment for breakthrough pain was adjusted according to the fentanyl dose, and immediate-release morphine or oxycodone was used for breakthrough pain. If patients were on anti-inflammatories, they remained on this medication. Patients recorded study data daily. Of the patients, 15.6% had the 72-hour patch changed to use every 48 hours. Mean frequency of daily rescue doses for breakthrough pain were analyzed.

• N = 45   
• AGE RANGE: 60–69 years
• MALES: 54.8%, FEMALES: 45.2%
• CURRENT TREATMENT: Not applicable
• KEY DISEASE CHARACTERISTICS: Varied tumor types
• OTHER KEY SAMPLE CHARACTERISTICS: Most were on 25–50 mcg fentanyl per hour.

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

• PHASE OF CARE: Late effects and survivorship
• APPLICATIONS: Palliative care 

• Retrospective cross sectional

• Numeric pain rating scale from patient diaries

Of the patients with suspected end-of-dose failure, 84% were switched to the once-a-day patch. The rest had patches switched at 48 rather than 72 hours. On the last day of the 72-hour patch, mean daily dosing for breakthrough pain was 3.61; on the third day after the switch, the mean daily dosing was 1.18 (p < 0.05). Adverse events occurred in 18% of patients with the new patch, including local skin irritation and sensitivity. Of the patients with shortened interval to 48 hours, three showed a decrease in pain score, two showed no change, and two showed increased scores. After the switch to the once-a-day patch, 61% showed more than a 30% reduction in average pain.

Patients switched to the once-a-day fentanyl patch had a reduction in average pain scores and a reduction in rescue medications needed.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Measurement validity/reliability questionable
• Timing of pain measurement from diaries is not stated.

Differentiating between breakthrough pain and end-of-dose pain medication failure is important. This study suggests that these may not always be well determined. Study findings suggest that a once-a-day fentanyl citrate patch may be more effective for pain control than the usual 72-hour fentanyl matrix, particularly in patients with end-of-dose failure. This study is limited by its design and sample size. Further well-designed research is warranted.

To determine whether biofeedback improves outcomes for patients with pelvic floor dysfunction (PFD), and to assess the relative effectiveness of different types of biofeedback therapy.

Databases searched were CINAHL, Embase, Medline, PsycINFO, Evidence-Based Medicine Reviews (EBMR), and the Cochrane Database. References of retrieved articles also were hand searched.

Search keywords were constipation, anismus, dyssynergia, obstructive defecation, rectocele, rectal intussusception, rectal prolapse, ​and biofeedback.

Studies were included in the review if they

• Were randomized controlled trials (RCTs)
• Reported on adults with PFD
• Included biofeedback as at least one of the treatments studied.

Studies were excluded from the review if they reported on pediatric cases.

The initial searching provided 5,028 references. Study selection and screening for inclusion criteria provided a final set of seven studies. Study quality was evaluated by two reviewers.

• The final sample of seven RCTs included 413 patients.
• Sample sizes ranged from 26 to 109.
• Medical diagnostic information across studies was not provided.

• Three trials compared biofeedback with other interventions such as laxatives, diazepam, and placebo. Meta-analysis showed an odds ratio (OR) of 5.861 (95% confidence interval [CI] [2.175, 15.794], p < 0.001) in favor of biofeedback.
• Four trials compared differences in biofeedback techniques. A meta-analysis of the most widely used technique, electromyogram biofeedback, showed an OR of 6.738 (95% CI [2.194, 15.58], p < 0.001) in favor of biofeedback.

• Results suggest biofeedback is associated with symptomatic relief of constipation; however, the number of studies included was very small and substantial heterogeneity existed across studies.
• Study quality overall was poor.
• Findings are not specific to the oncology population, and whether any of the studies included patients with cancer is not known.

Additional, better-designed studies are needed in this area to determine efficacy. Future studies should compare different biofeedback modalities to identify the most effective approaches.

The study's primary aim was to examine the effect of modafinil on persistent fatigue after treatment. Its secondary aim was to examine the effect of modafinil on cognitive function of patients with breast cancer.

In phase 1, participants were given 200 mg of modafinil daily for four weeks. Participants with a positive response in phase 1 were randomized to phase 2. In phase 2, participants continued to receive 200 mg of modafinil orally once per day or a placebo for four weeks. Repeated measures were completed at baseline (week 0), week 4, and week 8. Participants were stratified by treatment type: chemotherapy, radiation, or both chemotherapy and radiation. 

• The total number of participants was 82, with 76 completing phase 1 and 68 completing phases 1 and 2.
• The median participant age was 54, with a range of 33–83.
• All participants were female.
• All participants had breast cancer and were being treated with surgery and chemotherapy; 87% also received radiation.
• 75% of participants had at least some college education.

The study took place at the University of Rochester Medical Oncology Clinic in New York. 

The study was a prospective, open-label clinical trial.

• The Cognitive Drug Research (CDR) assesses domains of attention and memory, including speed of memory, continuity of attention, quality of episodic and working memory, and power of attention.
• The Brief Fatigue Inventory (BFI) assess fatigue.

Approximately 70% of the participants in the active treatment group had an improvement in continuity of attention from baseline to after treatment (week 8), compared with 52% in the placebo group; however, this difference was not statistically significant (p = 0.19).

In phase 1, modafinil had a significant effect on speed of memory (p = 0.0073) and quality of episodic memory (p = 0.0001). No significant effect in continuity of attention, quality of working memory, or power of attention was observed during this phase.

In phase 2, those who continued modafinil demonstrated significantly greater improvement in cumulative speed of memory (p = 0.029), quality of episodic memory (p = 0.0151), and continuity of attention (p = 0.0101).

Modafinil significantly improved some cognitive functioning, including speed of memory and episodic memory, but failed to demonstrate improvement in working memory.

• Findings were a secondary analysis; cognitive functioning was not the study's primary outcome.
• The study was an open-label trial, and thus participants were not blinded to their assignment.
• The study had a relatively small sample size.
• The majority of participants were an educated group of Caucasian women, limiting generalizability.
• The study did not report if differences existed between the original enrolled sample (n = 82) and those who completed the entire study (n = 68).
• Although not statistically significant, the participants assigned to the modafinil group had a mean age which was five years younger than the placebo group.
• Although the Cognitive Drug Research has been used reliably in other populations, it does not indicate if it has been used in cancer populations.