To review the effect of low-level laser therapy (LLLT) in the management of breast cancer-related lymphedema

Databases searched were MEDLINE, EMBASE, CINAHL, Center for Reviews and Dissemination, PEDro, and Cochrane Database of Systematic Reviews. Search keywords were breast cancer, lymphedema, and low level laser therapy. Studies were included in the review if they

• Were randomized controlled and uncontrolled trials. 
• Had a sample of women with unilateral lymphedema secondary to breast cancer surgery
• Had a sample that experienced a limb volume increase greater than or equal to 100 ml compared to the contralateral limb. 
• Compared LLLT  to no treatment, placebo, or another therapy.

The total references retrieved was 10. Literature was evaluated using Sackett''s levels of evidence. The PEDro Scale was used to rate the methodological quality of trials.

• The final number of studies included was eight. 
• The total sample across studies was 210 patients, with a range of 10–64.

The study has clinical applicability for late effects and survivorship.

A variety of doses and laser wavelengths were studied with different definitions for lymphedema.  3b dual wavelength scanning was used in three studies with favorable results. Hand-held 3b lasers were used in five studies where the laser was applied directly over fibrotic or congested areas. All doses were within the therapeutic window. In most studies, treatment was three times weekly with up to 18 total sessions over three to four months. Various methods were used to measure outcomes and reliability of measures was not discussed. Sometimes laser was used in combination with other co-interventions that could have influenced results.

There is moderate to strong evidence for effectiveness of LLLT for the management of breast cancer-related lymphedema.

• The review had a limited number of studies. 
• The variation of methods of outcome measurement and variability of LLLT treatment regimens makes comparison across studies difficult. 
• Co-interventions used in studies could intervene to affect results. 
• There were substantial baseline differences in study sample groups (the duration and severity of lymphedema varied greatly).

Findings suggest moderate to strong support for use of LLLT to manage lymphedema among patients with breast cancer. Research in this area needs to incorporate reliability of lymphedema measurement and common definitions of lymphedema

To review the Multinational Association of Supportive Care in Cancer (MASCC) guidelines for low- or minimal-emetic potential anticancer agents

Experts from MASCC met in Perugia in 2009 to revise the MASCC consensus guideline.

Searched keywords were antiemetic, low, minimal, guidelines, chemotherapy, dexamethasone, 5-HT₃ receptor antagonists, and dopamine receptor antagonists

Studies were included in the review if they involved chemotherapeutic agents with low or minimal emetic potential.

Studies were excluded from the review if they involved agents with moderate or high emetic potential.

The guidelines apply to multiple phases of care.

This review has applications for elderly and palliative care.

For chemotherapy with minimal emetic potential, the following is recommended.

• No antiemetic prophylaxis should be given in patients with no prior history of nausea and vomiting.
• Single-agent dexamethasone, 5-HT₃, or dopamine receptor antagonists should be given for nausea and vomiting.

For chemotherapy with low emetic potential, single-agent dexamethasone, 5-HT₃, or dopamine receptor antagonists should be administered.

More data is needed on the emetic potential and outcomes related to newer agents in oncology. A lack of clinical data is available on the emetic potential of some agents (e.g., cytotoxics, newer targeted agents), and the emetic potential has not been divided into acute or delayed.

To determine the effectiveness of the addition of a seven-day aprepitant dose to standard triple-drug antiemetic therapy for patients receiving multiday, highly emetogenic chemotherapy (HEC)

Patients were given 125 mg of oral apreipitant on day 1 and 80 mg of apreipitant on days 2-7, a 5-HT₃ on days 1-5, and 8 mg of dexamethasone on 1-8 for each cycle of chemotherapy.  Assessment of efficacy was performed via daily diaries, and analysis of outcomes was done for each chemotherapy cycle.  Rescue medication was lorazepam, metoclopramide, haloperideol, or prochlorperazine.

• The study consisted of 50 participants.
• The median age was 30 with a range of 19-60.
• The sample was 96% male and 4% female.
• All patients had germ cell cancer.

The study was conducted at a single outpatient site in Austalia.

This was a prospective, observational trial.

Patients recorded the number of vomiting episodes and severity of nausea and an 11-point numeric scale in diaries.

• The majority of patients (96%) reported no emesis on day 1, and an average of 82% (95% CI 68-91) had no emesis on days 1-7 in cycle 1.  This was maintained over 4 cycles, with more than 80% reporting no emesis on any day.
• Nausea was not as well controlled. In cycle 1, 71% of patients experienced no nausea on day one but only 27% reported no nausea days 1-7.  The pattern of nausea was similar for all cycles.
• Authors stated that adherence was good, but they did not report actual adherence to the medications.

This study adds to the current evidence for effectiveness of triple-drug antiemetic therapy for patients receiving HEC. The findings suggested that additional days of neurokinin 1 (NK1) may improve outcomes. The findings showed that nausea continues to be poorly controlled with current regimens.

• The sample size was small with fewer than 100 participants.
• A risk of bias exists because no control group, blinding, or random assignment was included in the study design.
• The outcomes reporting was selective.
• The measurement validity and reliability was questionable.
• No information on nausea severity or use of rescue medications was provided, so it was not clear how use may have varied and influenced results. 
• No data was provided on adherence or compliance with diary documentation of symptoms and episodes of vomiting.
• Findings cannot be directly compared to others because this study did not evaluate and define outcomes in terms of complete control per phase of chemotherapy administration.

Triple-drug antiemetic therapy for patients receiving HEC is the current established recommendation for management of chemotherapy-induced nausea and vomiting (CINV).  The addition of further NK1 may improve control. Although current therapies appear to control vomiting well, nausea continues to be a problem for patients.  Ongoing research aimed at nausea control is needed.

To determine if the use of aloe and mild soap versus mild soap (Dove) alone would decrease the incidence of skin reactions. Aloe gel included aloe vera, triethanolamine, d-α tocopherol (natural Vitamin E), carbomer, tetrasodium ethylenediaminetetraacetic acid (EDTA), methylparaben, and imdazolidinyl urea.

Participants were randomized to use aloe vera gel and mild soap or mild soap alone. The skin care regimen began on the first day of treatment. Aloe was to be applied liberally after treatment each day, reapplied throughout the day, and rinsed off prior to treatment (no time frame identified). Assessments were performed on day 1 and in weekly reviews. Clinicians could order supplemental skin products as they deemed necessary.

• The sample was comprised of 70 patients (34% male, 48% female).
• Age was: 45 years (18% in each study group), 45–59 years (55% aloe/soap; 32% soap alone), and older than 59 years (27% aloe/soap; 50% soap alone).
• Patients had cancer of the head and neck (39%), chest (58%), and extremities (3%).
• Mean cumulative dose was 2,700 cGy (range 900–7,209 cGy) for aloe/soap and 2,838 cGy (range 1,080–5,580 cGy) for soap.

Comprehensive Cancer Centre, University of Miami

The study was a prospective, randomized, blinded clinical trial.

• Weekly skin scoring was performed with Radiation Therapy Oncology Group (RTOG) acute criteria. 
• Other skin changes, such as texture, were recorded; there was no description of how these were assessed or measured.

The only significant difference found was delayed time to observation of a skin change with aloe in those with a cumulative dose greater than 2,700 cGy (p = 0.01).

No clear benefit of aloe vera was demonstrated.

• It was unclear if all assessments were made at the same dose intervals or only once weekly.
• Clinicians could order supplemental skin products as needed based on scoring severity of skin reactions. It was not possible to determine if the effect was related to aloe or other products.
• There was no documentation of skin reactions other than erythema or start to skin changes.
• No measures were described for the only significant finding.
• Patients were assessed weekly using RTOG, but no RTOG scores data were provided.
• The research question was “would aloe/soap decrease the incidence of skin reactions,” but the study was designed to assess delay to erythema. Data were not provided regarding overall incidence.
• There was a wide range of doses.
• Study conclusions stated were not supported by any data.
• The author stated the study was double-blind; however no control product was identified or discussed.

To evaluate the efficacy of Paullinia cupana in decreasing the number and severity of hot flashes in breast cancer survivors

The intervention consisted of 50 mg of dry extract of Paullinia cupana taken orally twice per day for six weeks. If patients presented unacceptable side effects, the intervention was stopped or the patient was removed from the study. All patients were trained to record each hot flash from a week before the initiation of the study until the sixth week. Severity was classified using published reports. The moments that were recorded took place at beginning of week 2 and then weekly until week 6. During each visit, patients' diaries were reviewed to check the severity of symptoms.

• N = 15  
• AGE RANGE = 36–65 years
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Breast cancer survivors undergoing hormonal treatment at least three months after chemotherapy or radiotherapy treatment
• OTHER KEY SAMPLE CHARACTERISTICS: May be on aromatase inhibitors or tamoxifen; must be having > 14 hot flashes per week

• SITE: Not specified
• SETTING TYPE: Not specified
• LOCATION: Brazil

• PHASE OF CARE: Transition phase after active treatment

Phase-II pilot study without a control group

• Diaries with self-reported scores were used by patients.
• The number and severity of hot flashes was scored from 1 (mild) to 4 (severe).

Of the 15 patients, 10 had a significant decrease greater than 50% in hot flash severity scores (p < .0001). The results demonstrated a statistically significant decrease in the number of hot flashes experienced by participants (p = .0009).

Although the authors reported a statistically significant decrease in the number and severity of hot flashes with the intervention of Paullinia cupana, there are many concerns regarding this study. The safety and purity of Paullinia cupana need to be established prior to recommendations of use.

• Small sample (< 30)
• Baseline sample/group differences of import
• Risk of bias (no control group) 
• Risk of bias (sample characteristics)
• Unintended interventions or applicable interventions not described that would influence results 
• Measurement/methods not well described
• Measurement validity/reliability questionable 
• Findings not generalizable
• Other limitations/explanation: In using a supplement that is not tested for purity and safety, many variables cannot be proven. Adherence to interventions could be compromised.

It is important to be aware of a supplement (Paullinia cupana) that has been reported to decrease hot flashes in women after breast cancer treatment. Nurses also need to understand that this supplement has not been tested by the U.S. Food and Drug Administration, so the contents of this supplement cannot be proven. This study does not report any adverse effects from the agent; however, caffeine is known to be associated with adverse side effects.

Databases searched were PubMed, PsycINFO, CANCERLIT, and Cochrane Library through May 2003.

Twelve randomized trials were included. Nonrandomized trials, pilot studies, and studies in which exercise was combined with other therapies, such as cognitive therapy or diet, were excluded.  Outcomes were fatigue, health-related quality of life, physical exercise capacity (maximal oxygen consumption), and other physical performance measures.  Treatment evaluated aerobic exercise training (10 studies) and resistance exercise (two studies).

• Sample sizes ranged from 21 to 155 patients.
• Nine studies included breast cancer patients, most of whom were stages I or II. The remaining studies included samples with mixed diagnoses, prostate cancer, and acute leukemia.
• In 10 of 12 studies, the intervention was conducted when patients were undergoing radiation therapy and/or chemotherapy treatment; two trials implemented exercise after the treatment was finished.
• Eleven of 12 studies were performed in patients receiving treatment with curative intent, and one study included a mix of patients receiving treatment with either curative or palliative intent.

Three studies reported a significant reduction in fatigue. One study observed a significant reduction in fatigue, although this did not reach statistical significance. In another study, no statistical analyses were performed to examine between-group differences.

The reviewed studies indicated promising effects on both physiological and psychological outcomes. However, the reviewed studies differed widely in the length of the exercise program, its intensity, content, and frequency, and the timing of the interventions in relation to the patient’s disease and treatment.

• In many of the studies reporting data on quality of life, too many outcomes were listed (range 2–12), and only four of the trials defined which variables were the primary endpoints.
• Randomized clinical studies are few, small in scope, and focus mainly on patients with breast cancer.
• Complete knowledge about the type of physical exercise most beneficial for patients at different stages of disease is lacking.

Future exercise intervention studies should also identify fewer and more specific endpoints.

To test the hypothesis that physical exercise reduces fatigue and improves physical performance in patients with advanced cancer.

Patients were randomly assigned to physical exercise (PE) or usual care (UC) groups. The PE group had two exercise sessions per week that lasted 50 to 60 minutes after a 10-minute warm-up. Exercise was performed in groups of two to eight and was supervised by a physiotherapist. Sessions included circuit training and stretching/relaxation. Focus was on muscle strength, balance, and aerobic endurance. Pre- and postintervention were performed at baseline at immediately after the intervention period.

• In total, 231 patients (62.3% female, 37.7% male) were included. 
• Mean age was 62.4 years (range 24–86). 
• Multiple types of cancer in advanced stage were included.
• Of the patients, 55% were receiving chemotherapy and 75% had a Karnofsky Performance Status score of 80 or greater.
• Of the patients, 65% had a baseline low level of activity of less than one hour per week.

• Multi-site
• Norway

• Patients were undergoing the end of life phase of care.
• The study has clinical applicability for palliative care.

This was a randomized, controlled trial.

• Fatigue questionnaire
• Physical activity prior to the study (none, <1 hour/week, 1-2 or 3 hours/week)
• Motivation (0-10 numerical scale)
• Physical performance tests: sit-to-stand, grip strength, maximal step length (balance), and shuttle walk (how far and fast one can walk) tests

Median survival times for all included patients were 11.1 months in the PE group and 12.3 months in the UC group. In the PE group, exercise adherence was 69% on average (11 of 16 sessions).  Regression analysis showed no significant between-group effect in physical fatigue (estimated mean difference = -0.3; confidence interval [-1, 1.0]; p = 0.62).  There were significant differences between groups in shuttle walk test (p = 0.008) and grip strength (p = 0.01) results. There were no apparent effects of the exercise intervention on mental or total fatigue, including mental and physical fatigue.

Findings showed that such an exercise program is feasible in patients with advanced disease and limited life expectancy. Findings did not provide support for the hypothesis that exercise reduces fatigue in this group of patients.

• The study lacked an appropriate control group.
• In the PE group, 35.5% of patients were lost to follow-up predominantly due to disease progression.

Exercise programs are feasible for patients with advanced disease. Study findings did not show that the intervention improved the symptom of fatigue, but it did improve some physical performance.

To test the effect, on pain severity and interference with daily life, of standard care versus care supplemented with pain education

Patients were referred by primary care providers and randomly assigned to the pain education program or standard care. The education intervention was provided in clinics and by telephone. Intervention included enhancing knowledge about pain and pain treatment.  Patients were contacted weekly by telephone. During each call they reviewed pain outcomes and side effects and received reinforcement education as necessary. In the report of the study, authors did not described standard care. The study was conducted over eight weeks. The study was originally designed to evaluate three groups; however, because of low recruitment the study compared only two interventions.

• The sample was composed of 59 patients. 
• Mean patient age was 59 years (SD = 11 years).
• Of all patients, 35% were male and 65% were female.
• The sample included patients with various tumor types; 82% of patients had metastatic disease.
• Average duration of pain was five months. All patients had nociceptive pain.
   

• Single site
• Outpatient
• Rotterdam, the Netherlands

Phases of care: multiple phases of care

Randomized controlled trial

• Brief Pain Inventory
• World Health Organization analgesic ladder (step scale)
• Pain management index
• Medication Event Monitoring Systems (MEMSs)
   

Average reduction in pain intensity declined in both groups. The decline was 0.8 (20%) greater in those receiving the intervention program (p = 0.03) than in those receiving standard care. Pain-related interference declined more in the intervention group (p < 0.01).  In the group that received the intervention, the percentage of patients who received both round-the-clock and as-needed medication increased: Of those receiving the intervention, 88% changed to this approach. In the group receiving standard care, 50% changed to the approach (p = 0.003). Adherence was initially the same across both groups. In the last two weeks, however, adherence was 74% in the standard-care group and 85% in the intervention group (p = 0.028).

The educational and support intervention was associated with greater decline in pain severity and pain-related interference, more aggressive pharmacologic management, and slightly better patient adherence over an eight-week period.

• The study had a small sample, with fewer than 100 participants.
• The study had a risk of bias due to no blinding.
• Authors noted that the study was underpowered.

Findings from this study support evidence that psychoeducational interventions can improve pain management and pain outcomes in patients with cancer-related pain. Incorporating such interventions and related follow-up programs into nursing practice can greatly benefit patients with chronic pain.

To describe the analgesic efficacy and side effects of parenteral hydromorphone among patients with severe cancer-related pain

Medical records were reviewed and data were collected retrospectively for patients admitted to a palliative care unit for pain management because of uncontrolled pain or severe side effects from their current pain regimens. Patients were started on parenteral hydromorphone. After starting the intervention, pain intensity and side effects were recorded twice daily. All patients had previously received opioids.

• N = 104      
• MEAN AGE = 57 years (SD = 13.5 years)
• MALES: 55%, FEMALES: 45%
• KEY DISEASE CHARACTERISTICS: 88% had metastatic disease and nociceptive pain
• OTHER KEY SAMPLE CHARACTERISTICS: Some patients were receiving chemotherapy or palliative radiation therapy. Some patients also were receiving ketamine during the study. Eighty-eight percent had had two or more previous opioid rotations. Median effective dose was 600 mg per day (range = 72–2592 mg per day).

• SITE: Single site    
• SETTING TYPE: Inpatient    
• LOCATION: Netherlands

• PHASE OF CARE: End-of-life care
• APPLICATIONS: Palliative care

• Retrospective, descriptive

• Numeric rating scale for pain
• Effectiveness determined as change in mean pain intensity at rest and with movement
• Time of adequate control was defined as first of at least two consecutive days with mean pain score of 4 or less, or physician was satisfied that pain was controlled

Adequate pain control was reported for 83% of patients, and among those who had improvement, the decline in mean pain score was significant (p < .001), ranging from a 2.7–3.1-point reduction. Seventeen percent had no response. Survival analysis showed continued effect of hydromorphone for 150 days for those who continued on the study (35 patients).

Switching to parenteral hydromorphone was effective for pain control in some patients who had either uncontrolled pain or severe side effects with previous pain medication regimens.

• Baseline sample/group differences of import
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Risk of bias(sample characteristics) 
• Unintended interventions or applicable interventions not described that would influence results
• Key sample group differences that could influence results
• Measurement/methods not well described
• Measurement validity/reliability questionable
• Other limitations/explanation: Differences in pain scores were used to show statistical significance, but the timing of measures used is not described, and authors state that where measurements were not available, physician satisfaction with control was used to show efficacy. It was stated that some patients were on ketamine, but it was not clear how much, who, or the potential impact on findings. A variety of coanalgesics were used, with no relevant subgroup analysis. There was extreme variability in baseline opioid dosages, suggesting highly varied baseline pain levels as well–range of baseline levels is not provided. Some patients also were receiving other palliative therapies, and analysis did not consider this.

Findings suggest that opioid rotation to parenteral hydromorphone was effective for some patients who had either uncontrolled pain or unacceptable opioid side effects. This study provides rather weak evidence because of numerous study limitations, but, for those patients at the end of life with intractable pain or significant adverse effects on current pain regimens, alternative approaches that may be effective are important to consider. Parenteral hydromorphone may be an appropriate alternative for these patients.

STUDY PURPOSE: To review the safety and efficacy associated with triple therapy (aprepitant, ondansetron, and dexamethasone) when given to children and adolescents receiving moderately emetogenic chemotherapy (MEC) and highly emetogenic chemotherapy (HEC)

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 3
• TOTAL PATIENTS INCLUDED IN REVIEW = 451
• SAMPLE RANGE ACROSS STUDIES: Unknown
• KEY SAMPLE CHARACTERISTICS: Aged 0.5–19 years; common diagnoses included bone cancers (Ewing sarcoma, rhabdomyosarcoma, and Hodgkin lymphoma).

Triple therapy with aprepitant, dexamethasone, and ondansetron had a 52% relative risk reduction in the development of chemotherapy-induced vomiting, and febrile neutropenia was not significantly different in patients receiving triple therapy compared to patients receiving dual therapy.

Triple therapy may reduce chemotherapy-induced vomiting in pediatric patients receiving MEC and HEC.

Pediatric patients receiving MEC and HEC may benefit from receiving triple therapy (aprepitant, ondansetron, and dexamethasone) for the prevention of chemotherapy-induced vomiting.