STUDY PURPOSE: To compare clinical trials examining outcomes with use of oral antifungal agents for prophylaxis in patients undergoing hematopoietic cell transplantation

• FINAL NUMBER STUDIES INCLUDED = 5
• TOTAL PATIENTS INCLUDED IN REVIEW = 2,147
• SAMPLE RANGE ACROSS STUDIES: 140–600 patients
• KEY SAMPLE CHARACTERISTICS: Not provided.

PHASE OF CARE: Transition phase after active treatment

Network meta-analysis using Bayesian statistical techniques were used. Results showed that voriconazole was the agent most likely to reduce incidence of overall probable or proven invasive fungal infection at 180 days post-transplantation. Mold-active agents voriconazole, itraconazole, and posaconazole were overall more likely to be effective than fluconazole as primary antifungal prophylaxis.

Findings suggest that primary antifungal prophylaxis with mold-active agents are more effective for patients undergoing allogeneic HCT.

• Few studies included

Primary antifungal prophylaxis with mold-active agents may be preferred to reduce probable or proven invasive fungal infections. Aspergillus tends to predominate invasive fungal infections in this group of patients. There is limited data directly comparing the various mold-active agents.

The evaluated treatment was antifungal prophylaxis with azoles (fluconazole, itraconazole, ketoconazole, and miconazole) or an amphotericin B formulation compared with placebo or no prophylaxis controls.

The search used MEDLINE and EMBASE (1966–2000); additional studies were identified from bibliographies/reference lists of articles, topical reviews, and information from the pharmaceutical industry and investigators in the field.

38 randomized, controlled trials

7,014 patients who received cytotoxic therapy for acute leukemia or hematopoietic stem cell transplantation (HSCT) sufficient to result in neutropenia (an absolute neutrophil count [ANC] of less than 1,000) lasting one week or more.

In severely neutropenic patients (ANC less than 1,000 for a week or more), antifungal prophylaxis reduced the use of:

• Parenteral antifungal therapy by 43% (prophylaxis success).
• Superficial fungal infection by 71%.
• Invasive fungal infection by 56%.
• Fungal infection-related mortality by 42%.

In subgroup analyses, superficial fungal infections were not reduced for:

• HSCT recipients overall.
• Patients receiving low-dose amphotericin B formulations.
• Patients in a single, small miconazole trial.

However, superficial fungal infections were reduced in HSCT recipients on azoles.

In subgroup analyses, fluconazole was more effective than itraconazole or low-dose amphotericin B formulations to prevent superficial fungal infections.

In subgroup analyses, a reduction in fungal infection-related mortality was not observed in:

• Pediatric trials.
• Non-HSCT trials.
• Trials comparing azoles with polyene controls.
• Trials comparing low-dose amphotericin B formulations with placebo.
• Trials with itraconzaole, ketoconazole, or miconazole.

There was a reduction in fungal infection-related mortality in trials using fluconazole for antifungal prophylaxis.
Antifungal prophylaxis did not affect:

• Overall mortality, except in subsets of HSCT recipients or patients in which the mean duration of neutropenia was longer than two weeks.
• The incidence of aspergillosis, perhaps because the overall incidence was low (1%) in both groups; therefore, a treatment effect could not be detected.

To investigate the feasibility of an intervention aimed at increasing exercise participation and improving dietary behavior in survivors of colon cancer and obtain preliminary data on the effect of the intervention on fatigue, exercise, and dietary outcomes.

Patients were randomly assigned to intervention or standard care control groups. The 12-week intervention included supervised and home-based exercise and dietary advice. During the first six weeks, the experimental group attended two group supervised exercise sessions of 30 minutes of aerobic exercise. Participants were asked to continue the same time of activities at home once a week during the same period and were asked to keep an exercise log. During the last six weeks, participants attended a supervised session once a week and were to perform two weekly home-based exercise sessions. Participants were given a dietary advice information pack and periodically attended healthy eating seminars encouraging reduction in saturated fat, increased fiber intake, reduction in refined carbohydrates, and limited alcohol intake.

• The sample was comprised of 18 survivors of colon cancer.
• Mean age was 69 years (range 52–80); 66.6% of patients were female and 33.3% were male.
• Of the patients, 83.3% had undergone surgery and one-third had received chemotherapy.
• Average time from the end of treatment was slightly greater than 16 months.

• Single site
• Outpatient
• United Kingdom

Patients were undergoing the transition phase after initial treatment.

This was a randomized, controlled trial that was single-blinded for some outcome measures.

• Godin Leisure Score Index for exercise behavior
• Functional Assessment of Cancer Treatment–Fatigue scale (FACT-F)
• Functional Assessment of Cancer Treatment–Colorectal scale (FACT-C) for quality of life
• Skeletal muscle fatigability assessed via electromyogram (EMG) signal analysis

There was an overall 90% attendance rate at supervised exercise sessions and a 77% attendance rate at dietary seminars. Of those in the intervention group, 66.6% returned exercise logs, and among these, there was a 94% rate of adherence to independent aerobic exercise for 25 to 30 minutes. There was no significant difference between groups in exercise behavior. Fatigue scores improved significantly in the intervention group (p = 0.005) compared to controls. There was a significant increase in dietary fiber intake (p = 0.044), with no other differences in dietary habits. Compared to controls, there were significant improvements in chair sit to stand performance (p = 0.003) and aerobic exercise tolerance (p = 0.01).

Combined supervised group and home-based individual exercise with dietary education was shown to be feasible and demonstrated preliminary positive effects on fatigue and dietary fiber intake.

• The study had a small sample size, with less than 30 participants.
• Standard care was not described.
• There is no information about other interventions or symptoms that might affect outcomes.
• The study design lacked an attentional control.
• There was a 6% dropout rate.
• There was a relatively limited time frame of follow-up.
• Given no difference between groups in exercise behavior overall, findings suggested that the group aspect with seminars and supervised exercise sessions may have been the important difference.

Findings suggested that an intervention combining some group supervised exercise and some home-based exercise is feasible and can be effective in reducing fatigue. Further research in this area is warranted as researchers attempt to determine the most effective ways to provide exercise interventions that patients will adhere to. The combination of some group periodic supervised sessions may improve patient motivations to adhere to a program, given the relatively low dropout rate seen here. This study was performed after completion of cancer treatment.

To analyze randomized, controlled trials (RCTs) comparing a single IV palonosetron dose to other serotonin antagonists for prevention of chemotherapy-induced nausea and vomiting (CINV)

Databases searched were Embase, LILACS, MEDLINE, SCI, CENTRAL, National Cancer Institute Clinical Trials service, Clinical Trials Register of Trials Central, American Society of Clinical Oncology, and American Society of Hematology and European Society for Medical Oncology abstracts.

Search keywords were palonosetron, random, chemotherapy, clinical trial, meta-analysis, practice guideline, randomized controlled trial, and review.

Studies were included in the review if they

• Were RCTs with parallel design that compared a single IV dose of palonosetron with other 5-HT₃ receptor antagonists (RAs) in patients receiving chemotherapy.
• Reported on patients receiving moderately or highly emetogenic chemotherapy regimens.

Initially, 324 references were identified. Five trials were used for final analysis. Two independent reviewers extracted study data and evaluated study quality and risk of bias. No specific methodology for this was described.

• The final sample was five studies involving 2,057 patients.
• Study sample sizes ranged from 50 to 667 participants.
• In three studies, use of corticosteroids was not allowed, and, in one study, corticosteroids were used concomitantly in a few patients.
• In all but one study, the primary endpoint was complete response during the acute phase.

• Overall from 0 to 120 hours, palonosetron was superior in the prevention of vomiting (relative risk [RR] = 0.79; confidence interval [CI] = 95%, 0.72–0.88; p < 0.00001).
• Palonosetron was more effective than other 5-HT₃ RAs in preventing acute vomiting (RR = 0.76; CI = 95%, 0.66–0.88, p = 0.0002) as well as late vomiting (RR = 0 0.76; CI = 95%, 0.68–0.85; p < 0.00001).
• Substantial heterogeneity was found (p < 0.05); however the superiority of palonosetron remained when one trial was removed from analysis with reduction in heterogeneity.
• In the study that used corticosteroids, no difference was found between palonosetron and other 5-HT₃ RAs.

• Palonosetron was more effective than other 5-HT₃ RAs for the prevention of acute and delayed CINV, when the drug regimen did not include corticosteroids.
• No difference in efficacy was found when other 5-HT₃ RAs were used in combination with a corticosteroid.

• Despite guidelines and recommendations that include the use of steroids, four out of the five trials included did not incorporate these.
• No subgroup analysis could be done between moderately and highly emetogenic chemotherapy regimens; therefore, it is not known if different CINV prevention regimens have different efficacy based on this factor.

To determine if use of mometasone furoate (MMF), a corticosteroid cream could reduce intensity of erythema in acute radiation dermatitis

Patients were randomized to receive tubes of either MMF cream 0.1%  or an emollient cream as a placebo control. Patients were instructed to apply the cream on the irradiated area twice a week up to 24 Gy and then once daily for the rest of treatment and three weeks after completion of radiation therapy. All patients in both study groups also applied the emollient cream over the radiated area once daily throughout the entire study period.

• The study sample (N = 50) was comprised of female patients with breast cancer who had undergone breast-conserving surgery.
• Mean age was 58 years for the MMF group and 60 years for the control group.
• All had a World Health Organization performance status of 0.
• A 5 MV photon beam was delivered in 2 Gy fractions for a total dose of 54 Gy.

The study took place in Uppsala, Sweden.

The study used a randomized double-blind controlled design.

• Skin reaction was measured with a seven-point grading scale, from 0 (no reaction) to 6 (moist desquamation) evaluated in five defined skin regions at each visit. Maximum scores were used in analysis.
• Patients’ subjective experiences of itching, burning, and pain were measured using a visual analogue scale.
• The Mann Whitney U test was used for all statistical comparisons.
• A reflectance spectrophotometer was used to rate erythema. The device emits various light colors corresponding to absorption peaks of hemoglobin and melanin.
• The intensity of emitted light as measured by a photo detector was used to provide a patient erythema index and a patient melanin index. These indexes were calculated as the mean of three assessments in each of five skin regions identified for each patient.

• The two-photon excitation was lower in the MMF group (p = 0.033)
• The maximal skin reaction grade was lower in the MMF treated group (p = 0.011).
• Six patients in the control group required further topical treatment because of severe subjective symptoms. Three patients in the MMF group needed further treatment of severe moist desquamation in the axilla.
• Patients in the MMF group reported less itching and burning, but the differences were not statistically significant.

MMF patients showed less pronounced erythema, less itching and less burning than emollient group. MMF may provide a benefit.

• The study had a small sample size, with less than 100 participants.
• Reliability of the seven-point scale was not stated, and it was not clear who was making observations.
• There was no log for application of the creams, so compliance with the planned regimen was not clear. The study did show that two patients did forget to apply the MMF during the treatment period.
• The study did not report if other skin regimens, such as washing, were allowed.
• Both groups applied the control emollient cream, so it is unclear what effect this had on skin reactions

To determine the effectiveness of using fentanyl buccal tablets (FBT) to reduce pain related to placing indwelling vascular access ports in opioid-naïve patients with cancer

Patients were assessed on anxiety and pain preoperatively. Ten minutes prior to the procedure, 100 mcg FBT was administered. Patients were assessed postoperatively on pain during the procedure. Side effects and symptoms were monitored during, after, and four hours after the procedure. Those with anesthesia-related nausea received one metoclopramide tablet one hour prior to the procedure, and those with extreme pain during the procedure received rescue therapy of 30 mg ketorolac or 20 drops of tramadol if allergic to NSAIDS/ASA.

• N = 65   
• AGE = 18 years and older
• MALES: 29.2%, FEMALES: 70.8%
• CURRENT TREATMENT: Not applicable
• KEY DISEASE CHARACTERISTICS: Histologically confirmed diagnosis of cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Participants were 18 years or older, had indication for port as an inpatient, were cognitively intact, and had written informed consent. Exclusion factors: xerostomia; treatment for chronic cancer pain with opioids; history of nausea and vomiting to opioids or intolerance to fentanyl or FBT; chronic respiratory insufficiency; hepatic or renal function impairment.

• SITE: Not stated/unknown   
• SETTING TYPE: Inpatient    
• LOCATION: Inpatient

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

• Phase II pre-/poststudy design

• Four-point Likert-type scale for pain
• State-Trait Anxiety Inventory Form Y (STAI-Y)

• Significantly lower perception of pain in those treated with FBT than those not treated with FBT (p = 0.0018)
• Drowsiness reduced from after procedure to four hours post-procedure (p < 0.01)
• Vertigo reduced from after procedure to four hours post-procedure (p < 0.02)
• No significant findings with respect to nausea, vomiting, vital signs, and other side effects

Use of FBT pre-procedure to reduce pain perception is a plausible intervention for pain control in those receiving a port but is not without side effects. Further consideration to prevent or ameliorate side effects and further studies with a larger population should be considered.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Risk of bias (no appropriate attentional control condition)  
• Risk of bias (sample characteristics)
• Unintended interventions or applicable interventions not described that would influence results
• Key sample group differences that could influence results
• Findings not generalizable
• These patients were compared to 2010–2011 patients, and so retrospective report and not knowing potential conditions impacting reporting is a weak area of this study

Nursing would need to be prepared for management of side effects and potential fall risk post-procedure. Side effects could require restructuring the postoperative environment to meet the needs of the patients or require follow-up beyond four hours.

To evaluate the relationship between antiemetic effect and well being over four different antiemetic treatment strategies

• The study consisted of a total of 162 chemotherapy-naive patients with ovarian cancer.
• All patients received similar combination chemotherapy, including cisplatin (50 mg/m²).

This study was conducted in the greater Stockholm, Sweden, area, with two gynecologic oncology wards.

Patients were randomly admitted to one of the two hospital wards for the study. Study II was a randomized, double-blind trial on the same hospital wards.

• Patients completed self-assessment questionnaires the day after and two weeks after chemotherapy.
• Presence, frequency, and intensity (on a 0–100 visual analog scale [VAS]) of nausea and vomiting was recorded. 
• Duration of acute nausea, including time of onset and number of hours until relieved, were recorded.
• Delayed nausea, including the number of days with any symptoms, was recorded for two weeks after chemotherapy.
• Questionnaires were administered regarding well-being before, during, and after chemotherapy.
• A 0–100 VAS was used to measure aspects of quality of life and well-being.

• Relief from delayed symptoms was highest in the group that received high-dose metoclopramide (2.5 mg/kg x 2), dexamethasone (20 mg x 1), lorazepam (1 mg x 2), and biperiden (1-2 mg x 3) followed by low-dose metoclopramide (20 mg x 3) orally for three days after chemotherapy.
• Nausea intensity was lowest in the group that received ondansetron (8 mg x 3) and dexamethasone (20 mg x 1) IV during the chemotherapy day and ondansetron orally (8 mg x 3) for five days after chemotherapy.
• Duration of acute nausea was shortest in the high-dose metoclopramide group. The high-dose metoclopramide and the ondansetron and dexamethasone groups reported better well-being.
• Duration of acute nausea was the only variable that was significantly related to well-being in both samples.
• Relaxation training was offered to 20 patients in the ondansetron and placebo group and 18 patients in the ondansetron and dexamethasone group; no differences were found in the studied variables.

• Some patients received a benzodiazepine, but no comparison regarding effect can be made.
• All patients had ovarian cancer, were in the same department, and were treated with similar chemotherapy.

To provide information about organizational experience with use of pegfilgrastim following dose intensive chemotherapy for solid tumors in pediatric patients with cancer.

Medical records of patients receiving myelosuppressive therapy supported with pegfilgrastim were reviewed (cases from 2007–2008). By protocol, pegfilgrastim was given in the outpatient clinic by subcutaneous injection at 0.1 mg/kg to a maximum does of 6 mg 24–48 hours after completion of chemotherapy. Complete blood counts (CBCs) were routinely monitored  every 7–10 days during therapy cycles, then every 2–5 days until neutrophil recovery. Analysis was limited to the first four courses of chemotherapy.

• 47 patients completed 176 courses of chemotherapy.
• Median age was 13 years, with a range of 2 months to 23 years.
• Females made up 53% of the sample; males made up 47%
• Key disease characteristics included Hodgkins disease, rhabdo myosarcoma, neuroblastoma, osteosarcoma, and Ewing sarcoma.
   

• Single site
• Outpatient
• Seattle, WA

• The phase of care was active antitumor treatment.
• The application was for pediatrics.

Retrospective descriptive

• Severe neutropenia was classified as an absolute neutrophil count (ANC) of less than 200 mm³
• Neutrophil recovery was an ANC greater than 200 mm³
• Febrile neutropenia was defined as severe neutropenia with temperature of 38.3ºC or higher with hospitalization and parenteral antibiotic therapy.
   

There were no significant adverse effects observed with pegfilgrastim. Leukocytosis was observed in 73% of patients, with no adverse sequelae. Severe neutropenia occurred in 57% of chemotherapy courses, and febrile neutropenia was seen in 28% of courses. Course delay occurred in 9% of courses, with a mean duration of two days of delay.

 This report provides evidence regarding the safety and efficacy of pegfilgrastim among a pediatric cancer population.

• Risk of bias (no control group) 
• Risk of bias (no blinding)  
• Risk of bias (no random assignment)
• Unintended interventions or applicable interventions not described that would influence results
• Key sample group differences that could influence results
• Retrospective study design with associated risk of bias in results. 
• No information is provided regarding any other prophylactic medications for prevention of infection in this population.

Findings suggest that pegfilgrastim is effective and can be safety given to pediatric patients.

To evaluate a method of mechanical lymphatic drainage using the RAGodoy apparatus

Lymphedema was confirmed with lymphoscintigraph and volumetry and defined as a difference in arm volumes of more than 200 ml. Patients had a one-hour session with the RAGodoy mechanical apparatus, which provides 15–25 elbow bending and stretching exercises per minute. Pre- and post-treatment volumetry was taken.

• The study sample was comprised of female patients with breast cancer who were experiencing arm lymphedema.
• The sample age range was 42–86 years.

The study took place at a single outpatient site in Brazil.

The study used a prospective trial design.

The reduction in the volume was an average of 59.2 ml (p < 0.001). In two cases, there was an increase in volume with the intervention. In the remaining 23, there was a decrease in volume. It appeared that for those where there was an increase, the patients did not fully allow the device to passively work.

Passive mechanical exercise for lymphatic drainage may be helpful in the management of lymphedema

• The sample size was small, with less than 30 participants.
• The report was brief with limited data and sample characteristics provided.
• The apparatus appeared to have been developed by the authors, so potential for bias must be considered.
• The study reported on single use only; repeated or longer-term use of the approach is unknown.

Use of a device for provision of passive limb exercise in the management of lymphedema requires further study.

STUDY PURPOSE: To explore the effectiveness of pharmalogic and nonpharmalogic agents in treating hot flashes in breast cancer survivors

TYPE OF STUDY: Systematic review

• FINAL NUMBER STUDIES INCLUDED = 4 nonpharmacologic and 22 pharmacologic
• TOTAL PATIENTS INCLUDED IN REVIEW = 1,930 patients (779 nonpharmacologic; 1,151 pharmacologic) 
• SAMPLE RANGE ACROSS STUDIES: 47–347
• KEY SAMPLE CHARACTERISTICS: Breast cancer survivors, clinical characteristics not specified and length of follow-up not described

PHASE OF CARE: Transition phase after active treatment
 
APPLICATIONS: Elder care

CAM therapies and vitamin E appear to have some effect, but data are limited. Gabapentin and some of the newer antidepressants were the most effective, with some side effects. These studies had small to moderate sample sizes, which makes overall effectiveness difficult to establish.

• Limited search
• No quality evaluation
• High heterogeneity
• Older article (2007)
• Hormone replacement therapy was not accepted by women

Nurses need to know the negative effects of hormonal agents on safety. Nonpharmacologic agents, such as soy phytoestrogens, black cohosh, and vitamin E, appear to be ineffective and limited because of the methodological limitations of studies. Gabapentin and some of the newer antidepressants were the most effective but still have side effects.