STUDY PURPOSE: To evaluate the effectiveness of exercise interventions compared with usual care on physical fitness, fatigue, and quality of life in patients treated with hematopoietic stem cell transplantation (HSCT)

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 9
• TOTAL PATIENTS INCLUDED IN REVIEW = 472
• SAMPLE RANGE ACROSS STUDIES: 19-105
• KEY SAMPLE CHARACTERISTICS: All had HSCT. Mean ages ranged from 29.1-55 years.

PHASE OF CARE: Active antitumor treatment

Six studies showed a positive effect on cardiorespiratory fitness (effect size [ES] = 0.53, 95% confidence interval [CI] [0.13, 0.94]) compared to usual care. Positive effects were seen in muscle strength. Five studies showed positive effects on quality of life (QOL) in global QOL (ES = 0.41, p = 0.0005), cognitive functioning (ES = 0.36, 95% CI [0.13, 0.59], p = 0.002) from the European Organization of Research on Treatment and Cancer (EORTC) self-report instrument. Compared to usual care, exercise had a moderate and significant positive effect on fatigue (ES = 0.53, 95% CI [0.27, 0.79], p < 0.0001).

Exercise interventions were shown to have a positive effect on cardiorespiratory fitness and fatigue, and might show some benefit in terms of several aspects of health-related quality of life for patients undergoing HSCT.

• Limited number of studies included
• Mostly low quality/high risk of bias studies
• Low sample sizes
• Single-item scale data were used for outcome measurement in areas of cognitive function and quality of life, and in two of those related to fatigue.
• High variability in the content, timing, and duration of interventions

This review adds to the body of evidence showing the effectiveness of exercise interventions for fatigue among various types of patients with cancer. Exercise may also have an impact on various aspects of health-related quality of life; however, the evidence in this area is weak, and additional research is needed to determine efficacy in this area.

To evaluate the efficacy of cocculine (a complex homeopathic medicine) in the control of chemotherapy-induced nausea and vomiting (CINV) in patients with nonmetastatic breast cancer who are undergoing standard chemotherapy regimens

Participants were randomized to receive standard antiemetic treatment plus either a complex homeopathic remedy (cocculine) and or the matching placebo in addition to standard antiemetic prophylactic (8 mg ondansetron [or 3 mg granisetron] and 80 mg methylpredinosolone twice daily). Cocculine is a registered remedy in France for the treatment of nausea and travel sickness. It contains four homeopathic components: Cocculus indicus, tabacum, nux vomica, and petroleum.

Patients were stratified by participating center and type of chemotherapy regimen. Study treatments (cocculine and placebo) were given as two tablets on the evening before chemotherapy; two tablets three times on day 1, and two tablets on the morning and evening of day 2.

Nausea and vomiting were monitored for five days by completing the Functional Living Index-Emesis (FLIE) on day 6. The study regimen was repeated in cycles 2 and 3, and symptoms were monitored until cycle 6.

• The study consisted of 431 patients.
• The median age was 52.8 years with a range of 20–74 years.
• All of the patients were female.
• Patients were chemotherapy-naïve with non-metastatic breast cancer and scheduled to receive six adjuvant cycles of chemotherapy including at least three initial cycles of 500 mg/m 95-fluoruracil, 50 mg/m adriamycin, and 500 mg/m cyclophosphamide (FAC 50); 500 mg/m 5-fluoruracil, 100 mg/m epirubicin, and 500 mg/m cyclophosphamide (FEC 100), or 75 mg/m docetaxel, 50 mg/m adriamycine, and 500 mg/m cyclophosphamide (TAC).
• To be included patients must have had no previous malignancies (except those in complete remission for more than five years), no contraindications to corticoids or 5-HT₃ receptor antagonists, and no prior treatment with cocculine or other antiemetics within the previous 15 days. Patients had to be able to be followed up with by phone.
• Patients were excluded from the study if they were pregnant or lactating.

The study was conducted at multiple outpatient sites in France.

All patients were in active antitumor treatment.

This was a randomized, multi-centered, double-blind, longitudinal, placebo-controlled, phase III trial.

• Patients measured nausea and vomiting by using the Functional Living Index for Emesis (FLIE) with five days recall (on day six for the first three cycles).
• A patient self-evaluation (EVA) daily diary was used to record nausea occurrence and intensity and the number of vomiting episodes on days 1–5.
• Investigators recorded adverse events using the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 3.0 (NCI-CTC AE V3.0). They also measured treatment compliance by intake of study drugs and counting returned drug boxes.

No difference was found between the two arms.

Adding a complex homeopathic medicine (cocculine) to standard antiemetic prophylaxis does not improve the control of CINV in patients just diagnosed with breast cancer.

• A risk of bias exists because of the sample characteristics.
• The investigators did not measure or control for history of alcohol consumption, nausea and vomiting during pregnancy, or anxiety level about nausea and vomiting before randomization.
• Because the study began on the first cycle of chemotherapy, the investigators had no chance to determine prior CINV experience or anticipatory nausea and vomiting.

Nurses should advise patients who use any complementary interventions that some can be ineffective and costly.

To provide practical guidance regarding the use of transdermal buprenorphine to treat cancer pain, particularly in those who need high-dose treatment to achieve pain control

• Of 122 articles retrieved, 22 were reviewed and made available to panel members before the November 2007 panel conference. Panel members contributed case reports for review. Authors provide points of discussion regarding several cases.
• Database searched was PubMed.
• Search keywords were buprenorphine, transdermal buprenorphine, neuropathic pain, and cancer pain.
• Attendance at the panel conference was funded by Grünenthal GmbH, the license holder of branded transdermal buprenorphine. The company paid the meeting chair's and primary author's honoraria. The primary author is a member of that company’s advisory board. Peer reviewers received honoraria from the parent organization of the company. The report states that the views expressed in the consensus statement are those of the expert panel and not necessarily those of the meeting sponsor.

The report provides information regarding the pharmacology and safety profile of transdermal buprenorphine. In addition, authors present some information, from studies and case reports, regarding efficacy. Authors provide no comprehensive review of search result or appraisal method. They do not detail the panel’s process.

• In identifying the benefits of transdermal buprenorphine in managing cancer pain, the panel concluded that the treatment
  • Is reliable and predictably efficacious.
  • Has antihyperalgesic potential.
  • Is effective, in low doses, at treating neuropathic pain. (Authors note effectiveness of transdermal buprenorphine compared to morphine.)
  • Has a favorable safety profile.
  • Presents a low risk of respiratory depression.
  • Is easy to use and convenient, involving a twice-weekly dosing schema.  
• The consensus was that transdermal buprenorphine
  • Is valuable in the treatment of cancer pain.
  • Is usable in combination with other opioids. (Authors note that no problems involving combination were reported.)
  • Offers advantages over other opioids in regard to treating neuropathic pain and mixed pain. 
• Authors identified the need for more research to determine best dosages and dose ceilings.

• The search was limited, as was the information the panel reviewed.
• Recommendations were created by consensus rather than based on standard appraisal of available evidence.
• A company that produces transdermal buprenorphine supported the work of the consensus group.

Expert opinion suggests that, for the treatment of cancer pain, transdermal buprenorphine is a useful alternative or adjunct to other medication.

To evaluate the compliance to radiation treatment planning of patients with bone metastases who have been premedicated with transdermal fentanyl

Fentanyl was delivered at 25–50 mcg/hour starting a week before treatment planning and during simulation. Immobilization devices were not mandatory.

• The sample was composed of 42 enrolled patients.
• Mean patient age was 68.5 years.
• Of all patients, 16 were male and 26 were female.
• Patients had epithelial cancer with skeletal metastases and strong pain uncontrolled by FANS and/or steroids. The most common primary cancers were breast and prostate cancers. All patients had 1–4 metastatic bone sites.
• Median pain score at first evaluation was 12 (the range of scores was 4–36), mean Karnofsky Performance Status Score was 60 (range, 40–80). In the sample were 47 treated metastases: 27 vertebral bodies, 11 of the femur, 3 of the humerus, and one of the pelvis.
• Patients were excluded if they had bone fractures or spinal cord compression; if estimated life expectancy was longer than three months; or if they did not have brain metastases.

Italy

Prospective study

• Pretreatment measures included physical examination; bone scan; x-ray; CT and/or MR scan; and Karnofsky Performance Status Score, with special emphasis on pain
• Modified Radiation Therapy Oncology Group (RTOG) scale (including domains measuring severity and frequency of pain and use of analgesic drugs), to measure modified pain
• Spitzer Quality of Life Index, or QL-I (0–10, with 10 being best quality of life), to measure quality of life
• Primary endpoint: patients’ compliance to maintaining established position
• Secondary endpoint: quality of life at end and at 40 days after external-beam radiation therapy

• Median pain score at treatment planning was 8 (range, 3–36).
• During simulation, 39 of 42 patients maintained position throughout the entire treatment period.
• The day after first external-beam radiation therapy, median pain score was 8. Median QL-I of 35 of 42 patients was 5 (range, 2–9).
• At end of treatment, pain score median was 6 (range, 1–36), QL-I was 6 (range, 2–10).
• Two patients died within 40 days of the end of radiation therapy.
• At 40 days after radiation therapy, median pain score of 40 patients was 3.5 (range, 0–24) and median QL-I score of 33 patients was 7 (range, 2–10).
• Treatment with fentanyl was well tolerated. The most common adverse responses were nausea, vomiting, constipation, and dizziness.
• According to the treating physician, 95% of patients maintained best position. This result suggests that patients’ comfort was acceptable.
• The intervention resulted in amelioration of quality of life for all patiients at end of radiation therapy and at 40 days after completion of therapy.

Transdermal fentanyl is efficacious and associated with minimal side effects.

• The study had a small sample size.
• Other factors affecting pain, such as use of analgesics, were not clearly defined. The scale accounted for such use in a general way but not specifically.
• Authors did not identify the specific drug being studied.
• During pain assessment, what was the site of pain? Was it at the site of metastasis or elsewhere?
• The treating physician decided whether a patient maintained the position. The report mentioned no quantitative measure associated with compliance.
• Were patients mobile? Where they at home or in an inpatient or hospice setting?

Previous studies have shown that perception of improved quality of life positively influences duration of survival.

To measure healing (defined as complete re-epithelialization of the wound) and injury progression during radiation therapy (RT).

Data were collected daily from the onset of wet dermatitis until its resolution.

All patients received routine care, as described in the departmental protocol for the treatment of radiodermatitis.

The agent used was Mepilex Lite—a nonadhesive, thin, absorbent foam dressing with a soft silicone layer and film backing.

Participants were examined weekly based on Radiation Therapy Oncology Group (RTOG) Assessment Criteria 0 to 4

• Level 1 or 2 radiodermatitis:  topical chamomile or low-dose corticosteroid cream, twice daily
• Level 2 or 3 radiodermatitis with loss of tissue integrity and moist/wet desquamation:  daily cleansing with low dose (10%) chlorhexidine, antibacterial creams, and application of test dressing.

At onset of moist/wet desquamation, daily records were kept regarding the progression of lesions with photographs and a pain assessment until full healing was achieved.

• The sample was comprised of 20 consecutive patients (60% male, 40% female) with specified diagnoses.
• Mean age was 50.6 years (range 18–81).    
• Of the patients, eight had breast; four had ear, nose, and throat (ENT); two had rectum; three had sarcomas; and three had lung/chest cancer.
• Patients were excluded if they had (1) any tumor other than breast, ENT, lung, cervix, and sarcoma; (2) stopped treatment; or (3) died during treatment.
• Patients were undergoing RT for sarcomas, ENT, breast, cervix, and lung cancers (high risk of skin toxicity). Informed verbal consent was obtained.

• Single site
• Radiation oncology department  
• Malaga, Spain

• Patients were undergoing the active treatment phase of care.
• The study has clinical applicability for late effects and survivorship.

This was an observational study with no blinding.

• RTOG radiodermatitis assessment scale used to assess the grade of radiodermatitis
• Daily photographs through full healing

All wounds (20/20) progressed to full healing.

No infections occurred.

Mean total healing time was 9.5 days (range 3–22 days).

Patient rating of experience (scale from 1 to 10, with 1 being the worst and 10 being the best)

• Atraumatic dressing:  10
• Convenience:  9
• Patient’s aesthetic perception:  9
• Ease of use for health professionals/family:  10
• Adaptability:  9
• Length of time adhesive held:  7

Positive clinical and patient-centered outcomes were observed.

• The study had potential for bias in results because it was noncomparative in design, with no randomization or controls.
• The study had a small sample size, with less than 20 patients. 
• Confounding variables of chlorhexidine and application of antibiotic creams were not addressed; which variable was responsible for healing?

Although the observational study showed efficacy and safety in a small number of patients, further studies need to be developed that include blinding, randomization, controls, and potential for multicenter involvement.

Moist wound healing has been shown in numerous studies to be beneficial for healing, although there have been conflicting results with the use of hydrocolloidal dressings. Consideration as to cost-effectiveness and patient ability to access dressings without significant out-of-pocket costs must be determined.

To assess the efficacy of ReCharge ice cream in reducing the number of days with chemotherapy-induced diarrhea (CID)

Eligible patients were randomized 1:1 to ReCharge or placebo, administered as one 11 g placebo serving or ReCarge daily for 10–18 days prechemotherapy and continued for six weeks from the start of chemotherapy.

• N = 197  
• AGE = 47–71 years
• MALES: 63.7%, FEMALES: 47.3%
• KEY DISEASE CHARACTERISTICS: All cancers
• OTHER KEY SAMPLE CHARACTERISTICS: Four weeks or more since last chemotherapy; starting first-, second-, or third-line regimen with cycles of two or three weeks; includes at least one of capecitabine, docetaxel, paclitaxel, 5-FU, or irinotecan

• SITE: Multi-site    
• SETTING TYPE: Outpatient    
• LOCATION: New Zealand

• PHASE OF CARE: Active antitumor treatment

• Randomized, controlled trials

• Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
• Functional Assessment of Chronic Illness Therapy-diarrhea subscale (FACIT-D)
• Primary intention to treat analysis
• Poisson regression model
• Patient diary
• Clinic assessments

The mean number of days with CID was not statistically significant on ReCharge versus placebo. There were no statistically significant differences between the treatment arms.

The study did not demonstrate effectiveness of ReCharge in reducing diarrhea.

• Risk of bias (no blinding)
• Selective outcomes reporting
• Key sample group differences that could influence results 
• Measurement/methods not well described
• Measurement validity/reliability questionable
• Findings not generalizable
• Intervention expensive, impractical, or training needs
• Many patients accrued were not included in study

ReCharge is not effective in CID management.

PURPOSE: To review an article with associated continuing medical education on the management of bleeding in patients with advanced cancer. Local interventions include suggestions for wound management.

• Includes eight references specific to dressing interventions for bleeding

• Packing with or without pressure—nose, vagina, rectum; packing swabs can contain hemostatic agents (i.e., acetone in vagina or cocaine in nose)
• Use nonadherent dressings.
• Frequency of dressing changes minimized to prevent trauma
• Topical dressings/ interventions include thromboplastin to control bleeding topically; absorbable gelatin topically or in the nose, rectum, or vagina; fibrin sealants; and collagen
• Vasoconstricting or cauterizing agents: epinephrine, silver nitrate, formalin, and alum

• Peer-reviewed journal intended to disseminate practice interventions
• Acknowledges that interventions are based on case studies and there is an overall lack of evidence

To develop, implement, and evaluate a group education program to prepare family caregivers who assume primary care for a relative/friend receiving home-based palliative care

Participants attended three group educational sessions (1.5 hours each) held over a three-week period in one of six palliative care service settings. Educational sessions involved education on the caregiver role, identification of palliative care services, strategies for responding to patient needs, strategies to maintain caregiver well-being, and specific content related to preparing for death and dying care. Evaluation of the intervention included participant completion of seven validated instruments (producing nine outcomes) before program commencement, following program completion, and two weeks following the program. Qualitative assessments also occurred via semistructured interviews with at least one participant per program (16) within two weeks of program completion and via facilitator journals to reflect perceptions of the program.

• The sample included 44 participants.   
• Mean age was 59.8 years, with a range of 39–84 years.
• The sample was 25% male and 75% female.
• Of the patients, 96% had cancer and 30% had been recently hospitalized; other information about patient disease characteristics is unknown.
• Of the caregivers, 43% had less than high school education and most worked outside the home. Most caregivers believed their health to be moderately good, had limited financial concerns, and overwhelmingly served as caregivers predominately to their spouse or child because they “wanted to be.”

• Multisite  
• Home setting
• Rural and urban care services in Australia

• End-of-life care phase
• Elder care, palliative care

A quasi-experimental, time-series design was used.

• Caregiver Competence Scale
• Preparedness for Caregiving Scale
• Family Inventory of Need
• Rewards for Caregiving Scale
• Social Support Questionnaire
• Brief Assessment Scale for Caregivers
• Life Orientation Test

A repeated measures analysis of variance on all nine variables over three testing times found multivariate effects for time (p < 0.001), including moderate associations between time and combined dependent variables (effect size by eta² = 0.36). The intervention had significant effects (p < 0.01 or better) on caregiver preparedness, perceptions of rewards, competence, and having needs met, and this effect was sustained up to two weeks post-program. Caregiver burden showed a significant (p < 0.001) increase between time 2 (post-program) and time 3 (two weeks post-program) of assessment, a finding perhaps related to poor patient prognosis. Social support and optimism levels appeared stable. Qualitative findings demonstrated overall favorable program feedback and appreciation of practical advice on available resources and symptom management provided.

This study found that a conceptually based psychoeducational group intervention for caregivers caring for a dying patient had some positive effects on caregiver preparedness, competence, rewards, and unmet needs. However, the program did not improve caregiver optimism, burden, or social support.

• The sample was small, with less than 100 participants.
• Risk of bias existed due to no control group and sample characteristics.*
• The study findings are not generalizable.*
• Subject withdrawals were ≥ 10%.
• Other limitations/*explanation: The study had substantial incomplete data, with only 59% of the sample completing all study measures.

Findings from this study continue to support the need for oncology nurses to assess and intervene with evidence-based programs focused on meeting the needs of caregivers of terminally ill patients. Results did not show an effect of the intervention to reduce caregiver burden; however, qualitative results desmonstrated caregiver appreciation of information on available resources and symptom management, pointing to the value of provision of this type of information to caregivers.

To evaluate whether buspirone alleviates dyspnea in patients with cancer and, secondary, whether it improves anxiety.

Patients with grade 2 or higher dyspnea per OCD tool were randomized to receive buspirone or placebo for a 28-day intervention on a fixed-dose titration. Treatment was discontinued after day 28. Baseline information was obtained including demographic info and MMRCDS. Assessments were then completed using OCD and STAI-S prior to starting protocol, within 5-7 days starting protocol, and after 28 days.

• N = 432  
• MEAN AGE = 64
• MALES: 46.5% drug/50.5% placebo, FEMALES: 53.5% drug/49.5% placebo 
• KEY DISEASE CHARACTERISTICS: Outpatient; any cancer diagnosis; receiving chemotherapy; have a screening score of grade 2 or higher per MMRCDS
• OTHER KEY SAMPLE CHARACTERISTICS: Older than age 18; had adequate renal, hepatic, and cardiac function; Hgb greater than 8; no transfusions in the past 15 days; pleural effusions drained or treated 

• SITE: Multi-site    
• SETTING TYPE: Outpatient  
• LOCATION: 16 sites in the United States

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

• Multicenter
• Randomized
• Double-blind
• Placebo-controlled

• Modified Medical Research Council Dyspnea Scale (MMRCDS)
• Oxygen Cost Diagram (OCD)
• Spielberger State-Trait Anxiety Inventory (STAI-S)

Buspirone did not significantly improve dyspnea or anxiety in patients with cancer.

Buspirone was not an effective treatment option for dyspnea in patients with cancer.

Buspirone should not be used as a treatment option for dyspnea in patients with cancer.

To summarize available literature on lymphatic microsurgery for breast cancer-related lymphedema

• Databases searched were PubMed and MEDLINE (2000–2012).
• Search keywords were lymphedema, microsurgery, surgical treatment, breast cancer, lymph node transfer, lymphovenous anastomosis, and lymph vessel transplantation.
• Studies were included in the review if they involved breast cancer treatment examining the effectiveness of microsurgical intervention.
• Studies were excluded if they involved primary lymphedema, lower extremity lymphedema, or mixed upper and lower extremity lymphedema.

• The total number of references retrieved were not reported.
• The checklist from the American Society of Plastic Surgery for therapeutic studies was used for quality assessment.

• The final number of studies included was 19 case reports involving a total of 191 patients.
• The sample range across all studies was 6–127.
• All patients had a breast cancer diagnosis.

Patients were undergoing the active antitumor treatment phase of care.

• Four retrospective case series (n = 52) reported results of composite tissue transfer. Findings were rate of reduction in circumference, reduction in pain, reduced incidence of cellulitis, and improvement in quantitative lymph flow.
• Two studies (n = 139) reported on lymph vessel transplantation. Outcomes included volume reduction and a case of donor site edema.
• Four prospective case series evaluated microsurgery. Findings from these studies were mixed. Studies differed in terms of including patients with early nonfibrotic lymphedema or chronic lymphedema. A number of significant methodological limitations in the evidence were reviewed. 
• Derivative microsurgery was associated with relief of neuropathic pain in two studies for 50%–100% of patients. 
• Three studies of inguinal lymph node transfer reported discontinuation of postoperative conservative therapy of variable rates for 3–24 months. Results were better with shorter duration of lymphedema. Minimal adverse effects were reported overall.

Very limited evidence exists regarding the efficacy of microsurgical techniques for the prevention and management of upper extremity lymphedema in patients with breast cancer who had axillary lymph node excision. The best findings were seen with inguinal lymph node transfer. Consistent positive findings and minimal reported adverse effects were reported. However, high quality-evidence is lacking.

Findings are limited because of the low number of studies, small samples, and lack of high-quality research. Additionally, follow-up duration varied, and most studies did not report rates related to the ability to discontinue conservative management for lymphedema.

Microsurgical techniques for the prevention of lymphedema are promising; however, further high-quality research studies with long-term follow-up are needed.