STUDY PURPOSE: To systematically review and quantify research on the effect of psychosocial interventions on pain in patients with breast cancer

TYPE OF STUDY: Meta-analysis and systematic review

DATABASES USED: Cochrane, PubMed, PsycINFO, EMBASE, Web of Science

KEYWORDS: breast cancer; pain; cancer-related pain; intervention; psychosocial; yoga; mindfulness; meditation; hypnosis; psycho-education; therapy

INCLUSION CRITERIA: Data on a psychosocial intervention; baseline and post-intervention pain measures; data on breast cancer populations; quantitative research

EXCLUSION CRITERIA: Patients younger than 18 years; non-English speaking; non-peer reviewed

TOTAL REFERENCES RETRIEVED = 163

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Independently reviewed by two raters who disagreed on 13 (8.7%); 0.71 kappa statistic for inter-rater agreement

• FINAL NUMBER STUDIES INCLUDED = 26
• TOTAL PATIENTS INCLUDED IN REVIEW = 2,193 women; 1,786 in analysis
• KEY SAMPLE CHARACTERISTICS: Patients with stage I–IV breast cancer; majority had completed treatment
   

• PHASE OF CARE: Multiple phases of care     
• APPLICATIONS: Elder care, palliative care

Psychosocial interventions overall were found to be effective. Robust effect size was found (g = 0.37) [95% CI 0.2–0.4]) but was smaller (g = 0.21) when adjusted for publication bias. Patient education approaches yielded a larger effect (g = 0.64) than supportive group therapy (g = 0.17).

Psychosocial interventions are effective in reducing pain in patients with breast cancer. Patient education and supportive group therapy appear to be the most effective interventions.

• Quality of research papers varied.
• Pain was not the primary outcome in most studies.

Nurses should employ psychosocial interventions to help ameliorate pain in patients with breast cancer. Education and support group interventions should be used initially because they appear to yield the greatest benefit.

To evaluate the efficacy of optimizing hot flash (HF) treatment, as determined by sleep and quality of life (QOL) measurements, by combining the hypnotic agent zolpidem with a selective-serotonin reuptake inhibitor (SSRI)/serotonin-norepinephrine reuptake inhibitor (SNRI) in a randomized, placebo-controlled, double-blind clinical trial.

All women were evaluated for current use of SSRIs/SNRIs for the treatment of HFs. If currently on an SSRI/SNRI for HFs, they were instructed to continue use. If they were nonusers, they were started on venlafaxine 75 mg per day. They were then randomized to receive zolpidem 10 mg each evening or placebo each evening for five weeks. Patients were evaluated at baseline and at the end of the study.

• The study enrolled 53 women with a mean age of 51.1 years (range 29.6–65.3 years).
• The women were being treated for breast cancer or were being managed for increased risk of breast cancer. 
• Adjuvant endocrine therapies were used by 71% of the women, with 29 taking tamoxifen.
• The level of perceived sleep disturbance was high.
• Patients reported HFs and awakenings, part of a clinical insomnia syndrome that was attributed to the HFs.
• Median time since diagnosis was 27.2 months (interquartile range 13.7–49.9 months).
• Patients must have completed therapy more than three months prior to enrollment.
• Menopause status varied.
• Women with primary sleep disorders or psychiatric disorders were excluded.

• Multisite
• Outpatient clinics
• Boston, Massachusetts

Patients were undergoing the long-term follow-up phase of care.

The study was a randomized, placebo-controlled, double-blind clinical trial. 

• Objective and subjective sleep HF measures:  sleep questionnaire, sleep diary, actigraphy using an actigraphic watch (Actiwatch-Score, Mini Mitter  Co, Inc. Bend, Oregon), skin temperature using the sterna lskin-conductance monitor (Biolog ambulatory recorder, UFI, Morro Bay, California), 7-day North Central Cancer Treatment Group Daily Vasomotor Symptom Diary    
• Beck Depression Inventory (BDI)
• Period of time awake after sleep onset (WASO) as determined by the actigraphic watch
• Pittsburgh Sleep Quality Index (PSQI)
• Quality of Life Inventory (QOLI)

Due to the high percentage of drop-outs in the placebo arm, the investigators changed the way they evaluated the results.  First, they identified the number of people who completed the study and showed improvement in sleep scores. The proportion of women completing the study varied by treatment assignment; 88% (22/25) of those who received zolpidem completed the therapy, whereas 57% (16/28) of those receiving placebo did so. Responders were those who completed the study AND showed improvement in their sleep scores. Forty percent (10) of the women taking zolpidem responded, whereas 14% (4) of the placebo group responded. Sleep improved in more women in the zolpidem arm than the placebo arm. The investigators looked at the differences in outcome measures between the two groups that completed the therapy. Measurements of PSQI scores and WASO time were significantly worse in the placebo arm. PSQI scores improved by 15% in the zolpidem arm and worsened by 26% in the placebo arm. The same was true with WASO time, which improved by 9% in the zolpidem arm and worsened by 2% in the placebo arm. In addition, patients in the zolpidem arm showed improvement in their QOL scores, whereas those on placebo showed a decrease in QOL scores. No change occurred in depressive symptoms in either group.

Zolpidem appears to improve a patient’s perception of nighttime HFs, perhaps by allowing her to sleep through the HF. Sleep scores improved, as did QOL in patients who augmented SSRIs with zolpidem for HFs. No change occurred in objective measurements of the number of HFs. Treatments targeting sleep may be an important supplemental strategy to optimize well-being.

• The study had a small sample size.
• The study had a high drop-out rate.
• The study had a heterogeneous sample.

Sleep disturbances due to HFs are among the most commonly reported symptoms in patients with breast cancer.  Augmenting SSRIs/SNRIs with zolpidem may improve perception of nighttime HFs and, in turn, improve sleep and QOL. Further study is required.

To investigate the efficacy and safety of vitamin K1 cream for cetuximab-associated acneiform rash

All participants in the research arm were given vitamin K1 (phytomenadione 0.1%, Reconval^® K1, manufactured by DRODERM^® in Slovenia) before initiating cetuximab therapy. A participant was to apply vitamin K1 to his or her face, anterior, and posterior trunk twice daily on day 1 and throughout therapy. Concomitant oral antibiotics were allowed for grades ≥ 2 acneiform rashes. Evaluation of compliance and observance of rashes took place at each clinic visit. The study population was compared to a historical control group that had received cetuximab-containing chemotherapy with or without oral antibiotics but without topical K1 cream. A dermatologist graded rash severity.

• N = 101
• AVERAGE AGE = 56.5 years
• MALES: 62% in study arm and 75% in control arm, FEMALES: 38% in study arm and 25% in control arm
• KEY DISEASE CHARACTERISTICS: Metastatic colorectal cancer with metastases to liver, lymph nodes, peritoneum, and/or lung. All patients were KRAS wild-type. 
• OTHER KEY SAMPLE CHARACTERISTICS: Study arm participants were ECOG 0–1, 93%, (> 2, 7%); control patients were 0–1 ECOG, 100%; no one in the study arm had received an EGFR inhibitor or had received topical or oral treatment for dermatologic reasons.

• SITE: Single-site  
• SETTING TYPE: Not specified  
• LOCATION: Asan Medical Center, Seoul, Korea

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

Non-randomized, open-label, interventional study with historical control

• National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI, CTCAE) v3.0 to grade rash severity

In the historical control, acneiform rash of any grade occurred in 97.5% of patients. In the experimental group, 88.5% of patients experienced any grade of rash. No significant difference was found between the groups. There was no significant difference between groups for the median time to rashes grades ≥ 1 or time to rashes grades ≥ 2. There was no significant difference in the overall occurrence of rashes grades ≥ 2 between the groups at any point. There was no significant difference in the time to improvement from grades ≥ 2 to grades ≥ 1 rashes.

Vitamin K1 is not an effective prophylactic treatment of acneiform rash associated with cetuximab treatment.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Findings not generalizable
• Other limitations/explanation: Data do not support the comparison of results to any other disease sites also using cetuximab therapy. Non-randomized, non-blinded trial.

Nurses should be aware that using topical vitamin K1 for prophylaxis of cetuximab-associated acneiform rash is not an effective treatment. Other interventions should be considered for patients receiving EGFR therapy for the management of acneiform rash.

To compare the therapeutic efficacy and safety of a single-dose of 0.25 mg or 0.75 mg palonosetron with first generation 5-HT₃ RAs (32 mg ondansetron, 100 mg dolasetron, or 3 mg granisetron) in preventing chemotherapy-induced nausea and vomiting (CINV) with or without IV dexamethasone before initiation of chemotherapy

Databases searched were Medline (1966 to June 2011), EMBASE (1980 to June 2011), American Society of Clinical Oncology, and National Cancer Institute (403 in total).

Search keywords were palonosetron, ondansetron, granisetron, dolasetron, nausea and vomiting.

Studies were included in the review if they were

• Incorporated a parallel-group or crossover design.
• Reported on adult patients receiving moderately or highly emetogenic chemotherapy.
• Provided sufficient data for evaluation of acute antiemetic efficacy.
• Included sufficient details on the adverse effects associated with palonosetron.

Studies were excluded if they had insufficient data on polanestron safety or if the participants were applied more than once in the review.
 

• A total of 16 references were retrieved.
• Homogeneity of effects across studies was assessed by using c2 statistical review.
• Publication bias was evaluated by using a visual inspection of the funnel plot of the fixed or random effect relative risk (RR) of each study on the x-axis and the standard error of the variance of the log RR on the y-axis.
• No evaluation was performed on the trials' quality.

• The final number of studies included was nine. Of these, four used 0.75 mg IV palonosetron.
• The total sample size was 3,463, according to the author (although counting the studies listed in Table 1 yielded a total count of 3,698, and checking each study separately yielded 3,776).
• The sample range of participants across studies was 89–1,114.
• Key sample characteristics were adult patients receiving MEC or higher with various cancer diagnoses.

• Patients were in active treatment.
• This study has application to palliative care and elderly care.

• Complete response (CR) was defined as no emetic episodes and no rescue medication used during the acute, delayed, and overall time intervals after initiation of qualifying chemotherapy. Complete control (CC) was defined as no emetic episodes, no need for rescue medication, and no more than mild nausea for the 0–24 hours, 24–120 hours, and 0–120 hours intervals.
• Compared with the first-generation 5-HT₃ receptor antagonists, the cumulative incidences of emesis were significantly reduced in the patients treated with palonosetron (0.25 mg IV) on the first day (RR = 1.11, 95% confidence interval (CI): 1.05–1.17), from 2 to 5 days (RR = 1.26, 95% CI: 1.16–1.36) and the overall five days (RR = 1.23, 95% CI: 1.13–1.34).
• Regarding drug safety, no significant differences were found between the group treated with palonosetron and the group treated with first-generation 5-HT₃ receptor antagonists.

Results from the analysis suggest that palonosetron is highly effective in preventing nausea and vomiting in the days after administration of moderately or highly emetogenic chemotherapy agents.

To evaluate the therapeutic efficacy and safety of aprepitant for the treatment of chemotherapy-induced nausea and vomiting (CINV) during the first five days following highly or moderately emetogenic chemotherapy

Databases searched were MEDLINE and Embase. Abstracts were searched in the American Society of Clinical Oncology, Cochrane Library, and National Cancer Institute.

Search keywords were aprepitant, MK-869, substance P receptor antagonist, NK-1 receptor antagonist, and chemotherapy-induced nausea and vomiting.

Studies were included in the review if they

• Were randomized controlled trials.
• Compared the efficacy of aprepitant with placebo or no intervention for the prophylaxis of CINV.
• Contained information regarding the complete control of vomiting or nausea during the first 24 hours or the first 24 hours after chemotherapy administration.
• Had at least 80% follow up.

Studies were excluded if they

• Involved patients receiving radiotherapy treatment.
• Only provided pharmacokinetic information.
• Included healthy people or animals.
• Involved patients with depression and other nervous system diseases.
• Had insufficient data on efficacy of aprepitant.
• Had subjects who were applied more than once.
   

• The total number of references initially identified was 327; of these, 29 were retrieved for detailed evaluation.
• The evaluation method was not specified.
• When abstracts and published articles were found on the same population, only the articles were used for analysis.
• When studies used a crossover design, only data during the first cycle was used for analysis.

• The final number of studies included was 15 representing a total of 4,798 patients (2,419 experimental and 2,379 control).
• The sample range across all studies was 45–866.
• Key sample characteristics were not specified.

All patients were in active treatment.

• Incidence of emesis was significantly reduced in the aprepitant group on the first day of chemotherapy (relative response [RR] = 1.13, 95% CI = 1.10–1.16). 
• Incidence of delayed nausea and vomiting from days 2–5 after chemotherapy was also significantly reduced (RR = 1.35, 95% CI = 1.22–1.48). 
• Aprepitant and ondansetron or granisetron demonstrated superior nausea and vomiting control compared to nonaprepitant regimens; however, aprepitant plus palonosetron did not show any superiority. 
• No significant differences were found regarding the occurrence of adverse effects in aprepitant versus control groups.

Aprepitant is effective in the prevention of delayed CINV. Aprepitant improves the antiemetic effect of ondansetron and dexamethasone in patients receiving cisplatin-based chemotherapy.

Aprepitant is effective and safe for the prevention of CINV in the acute and delayed phases of treatment.

STUDY PURPOSE: To appraise the effectiveness of nonpharmacologic pain management approaches in children and young adults with cancer

• FINAL NUMBER STUDIES INCLUDED = 32
• TOTAL PATIENTS INCLUDED IN REVIEW = 1,117
• SAMPLE RANGE ACROSS STUDIES: 8–124 patients
• KEY SAMPLE CHARACTERISTICS: The studies included various tumor types, and the majority involved acute procedure-related pain.

PHASE OF CARE: Active antitumor treatment

Six studies examining distraction, including music and virtual reality, showed mixed results. Nine studies used hypnosis, seven of which showed a positive effect on procedure-related pain. Sample sizes in these studies ranged from 23–80 (357 total) patients. Four studies used touch therapy, including healing touch, massage, and acupressure, with mixed results. Nine studies provided multimodal cognitive behavioral interventions including relaxation, procedure preparation, deep breathing, and other approaches. These showed mixed results. Aromatherapy and art therapy were examined in one study each.

The findings of this study suggested that hypnosis had relatively consistent positive results for the management of acute pain in this patient population.

All studies were identified as low-quality with only fair or poor internal and external validity. The USPS grading system was only designed to grade the level of individual studies, and it was not appropriate for all the study designs included.

The findings of this study suggested that hypnosis may be an effective intervention to reduce procedure-related acute pain in children and young adults. Its findings for touch therapy also showed some promise. Additional well-designed research with larger samples is needed to provide stronger evidence in this area. These findings were limited by the low quality of evidence included.

To assess the effects of methylphenidate (MPH) in ameliorating fatigue in patients with advanced pancreatic cancer

Records of patients with stage 4 pancreatic cancer who were experiencing fatigue were retrospectively analyzed. The fatigue level was assessed at each visit prior to chemotherapy, and a trial of MPH was done for at least four weeks. MPH was begun at 5 mg by mouth daily and increased to 10 mg for those who did not benefit from the lower dose.

• N = 71   
• AGE RANGE = 38–76 years
• MALES: 57.7%, FEMALES: 42.3%
• CURRENT TREATMENT: Chemotherapy

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: United States

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

Retrospective

• Visual analog scale-fatigue (VAS-F)
• Numeric scale

Most patients continued MPH after four weeks, for up to 24 months. Fatigue improved at least from grade 3 to grade 2, or from grade 2 to grade 1 in 55%; and in 23%, fatigue resolved. Fourteen percent stopped MPH because of lack of benefit, and 13% stopped because of adverse effects. The most common adverse effects were weight loss, nausea, anorexia, and insomnia.

MPH appeared to provide some benefit in reducing fatigue for some patients but had important negative side effects in others.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Measurement/methods not well described
• Subject withdrawals ≥ 10% 
• States use of VAS, but data reported appear to be from a 10-point numeric scale.  
• No statistical analysis was conducted.

The findings regarding any potential benefit of psychostimulants, such as MPH, for the management of cancer-related fatigue have been mixed. MPH has also been associated with a number of adverse side effects. Nurses need to be aware of side effects and relevant monitoring if MPH is used.

STUDY PURPOSE: To evaluate the overall efficacy of pain education among patients with cancer by using a meta-analysis of randomized controlled trials (RCTs)

TYPE OF STUDY: Meta-analysis and systematic review

DATABASES USED: PubMed, EMBASE, Cochrane Library

KEYWORDS: cancer; pain; education; counseling

INCLUSION CRITERIA: RCTs that included patients with cancer with pain, used an education intervention for cancer pain management, and presented pain intensity at baseline and after intervention

EXCLUSION CRITERIA: Duplicated studies; same study in more than one publication

TOTAL REFERENCES RETRIEVED = 213 (36 thoroughly reviewed)

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Two investigators independently reviewed and then compared discrepancies. Studies were rated on a 1–5 quality scale for RCT evaluation.

• FINAL NUMBER STUDIES INCLUDED = 12
• TOTAL PATIENTS INCLUDED IN REVIEW = 2,169 total patients; 1,069 patients enrolled in an intervention and 1,100 in a control arm
• KEY SAMPLE CHARACTERISTICS: Mean age was 57.2 years; 59% women

• PHASE OF CARE: Multiple phases of care     
• APPLICATIONS: Elder care, palliative care

• Overall pain education for patients with cancer showed a small but insignificant effect (standardized mean difference -0.11).
• Pain education was more effective in inpatients than outpatients.
• Pain education was more effective within two weeks of a first follow-up.
• A difference existed in the efficacy of the pain education based on pain intensity.
• Pain education was effective when tailored to an individualized patient. No beneficial effect was observed in high-quality studies, but lower pain was found in low-quality studies.
• Overall, insufficient evidence exists to support the use of pain education in patients with cancer.

This study showed that overall pain education in patients with cancer showed a small efficacy on pain relief in the meta-analysis of these RCTs.

• Authors note that many studies were not included because of lack of data.
• Predictors of pain response were not evaluated (e.g., age, socioeconomic status, education).
• Attention control inconsistent within the studies
• Quality of life or distress of pain on the patient not examined

Further studies are needed regarding the use of pain education on patients with cancer and the relation to pain relief. Because some patients benefited from the interventions, nurses may focus on situations in which patients received the most benefits (e.g., inpatients, patients with the most severe pain, education within the first two weeks of follow-up).

To determine the impact of bethanechol administration concomitant to radiotherapy on oral mucositis, candidiasis, and taste loss

Patients were randomly assigned to one of two treatment groups. Group 1 received 25 mg oral bethanechol, 3 times a day; group 2 received artificial saliva (OralBalance). Patients who experienced severe mucositis were subject to daily laser applications until remission of the lesions.

• The mean age of participants in the bethanechol group was 59 years and in the artificial saliva group was 55 years.
• The sample was 25% female and 75% male in both groups.
• Patients had been diagnosed with malignant neoplasms of the head and neck region and were receiving external beam radiotherapy (RT) encompassing one or more major salivary glands for a minimum of 45 Gy.

This was an outpatient radiation study conducted in Brazil.

Secondary analysis, stratified, open-label, random allocation to one of two groups.

• Mucositis was scored weekly using the World Health Organization (WHO) grading scale.
• Patients were examined weekly for Candida.
• Taste loss was defined as the patient’s subjective report of absence of taste.
• Fisher exact tests were used for categorical variables.
• t-tests were used for continuous variables.
• The Kaplan-Meier method was used.
• Log-rank tests were performed.

No significant differences in frequency and severity of mucositis, candidiasis, or taste loss were found.

Bethanechol did not appear to reduce the incidence of mucositis, candidiasis, or taste loss when administered during RT.

• The sample size was small
• Differences in the anticancer treatment regimen existed between the two groups.
• A wide variety of treatment protocols were used (bethanechol, sucralfate, and laser therapy).
• No delineation was provided as to the type of chemotherapy that patients received. Possible implications exist (e.g., perhaps taste was a factor of chemotherapy).

Larger, randomized, double-blind, placebo-controlled studies are needed possibly to further test the hypothesis that bethanechol could minimize RT-induced mucositis incidence or severity.

The intervention was directed at patients and caregivers (primarily at patients). The standardized nursing intervention protocol included three home visits and six telephone calls over four weeks from an oncology clinical nurse specialist. Intervention activities included

• Problem assessment and monitoring
• Symptom management and teaching of self-care behaviors
• Coordination of resources.

• The sample was comprised of 161 family caregivers of patients older than 60 years.
• Patients
  • Were newly diagnosed (in the past two months) with solid-tumor cancers
  • Were currently hospitalized for surgical cancer treatment
  • Had a prognosis of six months or greater
  • Lived within 50 miles of the study center
  • Had a complex problem at the time of discharge.

Home setting

A controlled trial design was used, with a major limitation.

• Caregiver reaction assessment
• Center for Epidemiologic Studies–depression

No significant differences existed on any outcome measure. No effect on caregiver esteem was found. Among caregivers with physical problems, those in the treatment group had an increase in lack of family support between interviews 1 and 2 followed by a decrease between interviews 2 and 3. Control group subjects displayed the opposite pattern. Caregivers with physical problems had greater decreases in difficulty with finances than those with no physical problems. Caregivers in the control group had a decrease, whereas those in treatment group did not. No significant effect on depression was found. Caregivers in the control group had a decrease in the effect of providing care on physical health between interviews 1 and 2 and then remained constant between interviews 2 and 3. Caregivers in the treatment group displayed the opposite pattern. The analyses are based on some caregivers who had received nonprotocol home care and were dropped from analyses.

Little information is presented on the details of the intervention. The control group had some contamination (32.4% of the control group and 32.2% of the intervention group received referrals for home care that were not connected with the study). Findings were difficult to interpret.