• FINAL NUMBER STUDIES INCLUDED = 10 
• TOTAL PATIENTS INCLUDED IN REVIEW = 2,534
• SAMPLE RANGE ACROSS STUDIES: 30–282 patients
• KEY SAMPLE CHARACTERISTICS: Multiple types of cancer were represented across studies.

Interventions included exercise in eight studies, sleep hygiene in seven, relaxation training in six, and nutritional guidance in six. Six studies included the use of a booklet as supplement material. Four studies included telephone follow-up, and one was provided via an Internet-based program. The program duration ranged from 1 week to 12 weeks. Attrition rates ranged from 7%–46.7%. Two studies demonstrated significant reduction of fatigue with ES ranging from –0.76 to –1.41 (p < 0.001). Six studies concluded achieving a limited positive effect, with a small effect size and no statistical significance. One study showed no effect, and one showed worse outcomes in the intervention group. High heterogeneity existed across trials, so no meta-analysis was deemed appropriate.

Inconsistent evidence of effects of patient education programs on cancer-related fatigue existed across all 10 studies.

• Variability of cancer types, stages, treatments, and phases of care across studies
• Various types of control conditions could contribute to bias.
• Variability existed in program duration, methods of delivery, and follow-ups.
• High attrition existed in some studies.
• Many studies included exercise, which alone has been shown to be of benefit for fatigue.

Some mixed evidence exists regarding the effects of patient education programs on cancer-related fatigue, which are related to the variability in interventions that have been studied. More rigorous research is needed to sort out those program characteristics and populations of patients who can benefit most from educational interventions.

The purpose of this study was to determine if guideline-based antiemetic therapy would improve chemotherapy-induced nausea and vomiting (CINV) in patients with multiple risk factors for CINV

• N = 152 
• AGE RANGE = 26–76 years
• MEDIAN AGE = 54 years
• MALES (%): Not provided, FEMALES (%): Not provided
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Early-stage breast cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Anthracycline-based chemotherapy

• SITE: Multi-site   
• SETTING TYPE: Multiple settings    
• LOCATION: Canada

• PHASE OF CARE: Active antitumor treatment

• Randomized controlled trial (RCT)

• The Functional Living Index-Emesis (FLIE) was used to measure the impact of CINV on the patients' quality of life. This assessment was given to patients on day 5.
• Patients used a diary daily to record the frequency, intensity, and duration of CINV. This diary was used for the first five days post administration of chemotherapy. The research nurse called the patient on days 1 and 5.

Patients from all risk levels had similar rates of acute and delayed vomiting; however, acute and delayed nausea remained higher in the high-risk patients.

• Findings not generalizable
• No report of comparison of outcomes across study groups

By assessing patient risk factors for CINV and prescribing antiemetic therapy based on patient risk stratification, acute and delayed vomiting may be managed; however, acute and delayed nausea remained significantly higher in the highest risk patients.

To evaluate the effectiveness of oral dexamethasone in attenuating or eliminating ​palmar-plantar erythrodysesthesias (PPE) induced by pegylated liposomal doxorubicin (PLD) (Doxil^®) in patients with recurrent gynecologic malignancies.

Patients were initially treated with PLD without dexamethasone (median number of cycles = 5). Patients who experienced grade 2 to 4 PPE had treatment delayed until symptom resolution, and then were retreated without dose reduction.

Patients in group 1 received a tapering oral dexamethasone regimen (8 mg BID) starting one day before infusion for five days, 4 mg BID on day 6, and 4 mg on day 7.

In group 2, patients who were not receiving dexamethasone and experienced grade 2 to 4 PPE had a weekly dose delay for up to two weeks until symptom resolution. If resolution occurred within three weeks of the delay, a 25% dose reduction was made. Patients who had persistent grade 3 or 4 PPE had PLD withdrawn.

• The study reported on a sample of 23 patients with recurrent gynecologic malignancies who received PLD 50 mg/m² on a 28-day cycle from January 1998 to December 2000.
• Sixteen patients had ovarian cancer, and seven had uterine cancer.

University of Texas Southwestern Medical Center in Dallas

This was a prospective, observational trial.

National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) was used to assess PPE (grades 1–4).

• Nine patients (39%) who received more than five cycles of PLD (50 mg/m²) developed grade 2 to 4 PPE. Median time to PPE was three cycles, and drug treatment was withheld until PPE symptoms resolved.
• On restarting treatment, six of nine patients who developed PPE received a scheduled tapering dose of oral dexamethasone. All six had complete or near complete resolution of PPE, and all continued treatment without subsequent dose modification or delay for an average of seven cycles.
• In group 2, three of the nine patients with PPE who did not receive dexamethasone required treatment delays, and doses were reduced.

Oral dexamethasone appears to be effective in attenuating or eliminating PLD-induced PPE in patients with recurrent gynecologic malignancies.

The sample size was small.

PHASE OF CARE: Active antitumor treatment

883 patients across studies did not receive G-CSFs, of which 21.97% developed FN (adjusted rate 23.2%). Compared to patients who did not receive G-CSFs, patients who received G-CSFs had an OR of 0.077 (95% CI [0.013, 0.460]), a 92.3% lower incidence rate. Patients younger than age 65 also had a lower rate of FN (4.2%–66.7%) compared to patients 65 and older (7.7%–88.2%).

Use of G-CSFpp significantly reduces the risk of FN in patients with early-stage breast cancer receiving TC therapy. Patients younger than age 65 also have a reduced risk of FN compared to patients 65 years and older.

The reporting of findings differed between use of G-CSF (OR) and no use (%). They did report a 93% lower risk with use of G-CSF. The reporting of age differences did not differentiate between use or no use of G-CSF.

Aside from the limitations noted above, use of G-CSF as primary prophylaxis reduces the risk of FN in this patient population. Oncology nurses should be aware of the risks of FN in patients being treated with TC for early-stage breast cancer and promote use of G-CSFpp.

To evaluate the effectiveness of foot massage on pain in patients with cancer 

This research was a nonrandomized, two-group, quasi-experimental time series design conducted among 60 patients with cancer. The experimental group received a 30-minute foot massage over a three-day period. Pain was assessed using the Numeric Rating Scale for pain, which used a 0–10 range. Pain was assessed prior to the intervention and after the intervention for three days.

• N = 60  
• AGE RANGE = 39–58 years
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Diagnosis of cancer within last one to three years with chronic-type pain in the second stage of cancer
• OTHER KEY SAMPLE CHARACTERISTICS: All were Hindu

• SITE: Single site    
• SETTING TYPE: Inpatient    
• LOCATION: Devaki Cancer Hospital and Research Institute in Madurai, India

• PHASE OF CARE: Transition phase after active treatment

Nonrandomized, two-group, quasi-experimental, time series trail

• Numeric Rating Scale (NRS) for pain

On day 1, all patients in both groups reported severe pain. On day 2, most of the patients reported moderate pain with no measurable differences between the two groups. On day 3, the experimental group reported mild to no pain, and there was no change in the control group from day 2. The intervention group experienced a significant reduction in pain (p < 0.001).

This study shows the need to understand the purpose of foot massage techniques on pain levels in patients with cancer. The researcher assumed that with a decrease in pain, there would be an increase in patients' quality of life including stability in physiologic, psychological, sexual, vocational, and lifestyle aspects. These areas were not measured, and additional research is needed.

• Small sample (< 100)
• Baseline sample/group differences of import: Did not identify types of cancer
• 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: Did not identify any medications given for pain
• Key sample group differences that could influence results: Cancer diagnoses not identified
• Measurement/methods not well described: Unclear when intervention was done in response to pain assessment  
• Findings not generalizable
• Other limitations/explanation: The use of the NRS for pain is very subjective. It is unclear when or where the assessment was done in relation to the intervention. Although all the patients were female, the types of cancer studied were not reported. Different types of cancer can cause many different types of pain in different locations. The second stage of cancer was not defined. The types of pain medications used were not defined. The positions of those providing the intervention and their training were not identified. It is unclear if the foot massages were done consistently between patients using similar techniques.

Foot massage is an easy and cost-effective nursing intervention that could be used to help ease patient pain. This research article identified the need to continue research in this area. The patient parameters need to be more specific in future research designs.

To evaluate the overall effectiveness and safety of neurokinin 1 (NK1) receptor antagonists (RAs) in the prevention of chemotherapy-induced nausea and vomiting (CINV) when compared to standard antiemetic regimens including a 5-HT₃ RA plus dexamethasone

Databases searched were MEDLINE, Embase, Cochrane Central Register of Controlled Trials (Central), and Latin American and Carribean Health Sciences Literature (LILACS).

Search keywords were neurokinin, aprepitant, casopitant, ezlopitant, netupitant, vestipitant, chemotherapy-induced nausea and vomiting, nausea in cancer patients, vomiting in cancer patients, and randomized trials.

Studies were included in the review if they

• Were randomized controlled trials (RCTs) that addressed the addition of an NK1 RAs to standard antiemetic therapy (dexamethasone plus 5-HT₃ RA) for the prevention of CINV.
• Provided an adequate description of outcomes that could be pooled in the meta-analysis.
• Used adequate antiemetic therapy in the control arm.

No specific exclusion criteria were identified.

A total of 4,034 references were retrieved.

Two reviewers assessed the quality of each study. Items from Delphi list and Jadad score were utilized for data extraction; however, the authors did not describe if any specific scoring system was used for quality assessment.

• The final number of studies included was 17.
• The sample range across all studies was 36–1,933.
• The total number of patients included in the review was 8,740. Data from 8,173 patients in 13 studies were used for analysis about complete response (CR), which is defined as no vomiting, no retching, and no use of rescue medication. Data from 8,376 patients from 15 studies were used for acute and delayed phase analysis.
• All patients were diagnosed with cancer and receiving either highly or moderately emetogenic chemotherapy.

All patients were in active antitumor treatment.

• The use of an NK1 RA increased the CR rate in the overall phase from 54% to 72% (overall response [OR] = 0.51, 95% confidence interval (CI) = 0.46–0.57, p < 0.001), in the acute phase (OR = 0.56, 95% CI = 0.48–0.65, p < 0.001), and in the delayed phase (OR = 0.48, 95% CI = 0.42–0.56, p < 0.001).
• The addition of an NK1 RA to standard antiemetic therapy improved CR rates in the overall phase for patients who received highly emetegenic chemotherapy (OR = 0.46, 95% CI = 0.40–0.53, p < 0.001) or moderately emetogenic chemotherapy (OR = 0.59, 95% CI = 0.51–0.67, p < 0.001).
• The addition of an NK1 RA increased CR rates in the overall phase independently depending on if ondansetron was used in the control arm beyond day 1 or not (ondansetron: OR = 0.64, 95% CI = 0.54–0.76, p < 0.001; no ondansetron: OR = 0.47, 95% CI = 0.41–0.53, p < 0.001). CR in the acute phase and delayed phase demonstrated a strong correlation (r = 0.91, p < 0.001).
• Three trials (n = 1,480) suggested a statistically significant increase (from 2% to 6%) in the risk of severe infection among patients receiving NK1 RAs (OR = 3.10. 95% CI = 1.69–5.67, p < 0.001).

The addition of an NK1 RA increased CINV control in the acute, delayed, and overall phases.

The use of an NK1 RA may be associated with a statistically significant increase in the risk of severe infection. A more comprehensive evaluation of the safety profile of NK1 RAs and additional appraisal of specific data from RCTs is needed.

• Subgroup analysis requires careful scrutinization. In this review, most patients in the moderately emetogenic chemotherapy group received an AC regimen, which is now considered highly emetogenic chemotherapy.
• Favorable ondansetron use for the delayed phase was suggested after comparing its effect with placebo control. However, current guidelines suggest the use of dexamethasone rather than ondansetron as a combination regimen for delayed CINV control. Comparison should have been between an NK1 RA plus dexamethasone versus NK1 plus ondansetron.
• Toxicity analysis was based on reports  of 3 studies (out of 17 studies included) which reported on the most prevalent adverse events. NK1 RA use did not increase the risk of febrile neutropenia or any other hematologic toxicity. OR findings are not clearly interpretable.

• This systematic review summarized the results from RCTs which investigated the effect of an NK1 RA for CINV control. Overall, the use of an NK1 RA improved the CR in acute, delayed, and overall phases.
• Further studies are warranted to determine whether adding an NK1 RA to standard antiemetics could improve CINV control in non-AC, moderately emetogenic chemotherapy as most NK1 RA RCTs were based on cases receiving highly emetogenic chemotherapy (including an AC regimen).
• Although further study is warranted, occurrence of infection with NK1 use requires special attention.

To determine if the use of guarana extract affects fatigue or quality of life in patients with head and neck cancer undergoing chemoradiotherapy

Patients were randomized to receive either guarana or placebo, with both given twice daily before meals for six weeks while they were undergoing chemoradiotherapy. The patients receiving guarana took 50 mg twice daily. The patients were assessed three times throughout treatment at day 1, day 21, and day 42, and once three weeks after the completion of treatment on day 63. The three assessments during treatment corresponded with cisplatin administration. Each assessment included fatigue and quality of life questionnaires, evaluation for guarana toxicity according to the World Health Organization scale, as well as weight and renal function.

• N = 52   
• AGE = Not specified
• MALES (%): Not specified, FEMALES (%): Not specified
• CURRENT TREATMENT: Combination radiation and chemotherapy
• KEY DISEASE CHARACTERISTICS: Stage I–IV head and neck cancer, mainly squamous cell carcinoma. Patients underwent 30 sessions of radiotherapy and three cycles of cisplatin.

• SITE: Not stated/unknown   
• SETTING TYPE: Not specified    
• LOCATION: Brazil

PHASE OF CARE: Active antitumor treatment

Phase II, placebo-controlled, double-blind, randomized study

• General questionnaire
• Guarana Toxicity Assessment 
• Functional Assessment of Cancer Therapy-Fatigue (FACT-F)
• Functional Assessment of Cancer Therapy-Head and Neck (FACIT-HN), version 4.0
• European Organization of Research and Treatment of Cancer Core Quality of Life (EORTC QLQ-30) questionnaire
• EORTC QLQ-H&N-35 questionnaire

No statistically significant reduction in fatigue or improvement in quality of life was identified in either group using any questionnaire. Some initial or transient improvements were noted but were not statistically significant or did not last the length of treatment. The authors do not recommend the use of guarana in this patient population.

This intervention was not successful for this patient population. Although the authors reported some positive benefits, based upon the description of the results, it is unclear if this is related to the guarana or other factors that could influence quality of life in the patient population.

• Small sample (< 100)
• Measurement/methods not well described
• Subject withdrawals ≥ 10%

In terms of nursing practice, this study highlights the significance of malnutrition, weight loss, and mucositis in this patient population, and addressing these complications of chemotherapy and radiation in this patient population seems like a promising area for nursing attention and research.

Proteolytic enzymes comprised of papain (100 mg), trypsin (40 mg), and chymotrypsin (40 mg) were administered orally 3 x 4 tablets per day.

The study reported on 69 patients with tumors of the oropharynx or oral cavity undergoing a radiation dose higher than 40 Gy.

The study was conducted at a multicenter site from June 1996 to May 2000.

This was a prospective, randomized, triple-blind, placebo-controlled, parallel group study.

• Maximum grade of mucositis was recorded.
• The Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) toxicity criteria were used.

No statistically significant difference was found in analysis. Treatment with Wobe-Mugos E resulted in an earlier onset of mucositis and increased average scores for treatment duration.

The sample was not sufficient according to power analysis.

The primary objective was to evaluate the safety of caspofungin (CAS) in pediatric patients following allogeneic hematopoietic stem cell transplantation (HSCT) when compared with intravenous (IV) liposomal amphotericin B (L-AmB).  The secondary objectives evaluated the incidence of aspergillosis, candidiasis, and other fungal infections in pediatric patients following allogeneic HSCT.

This was a retrospective analysis of pediatric patients receiving either CAS or L-AmB after allogeneic HSCT between January 2006 and June 2010.  All patients received L-AmB (1 mg/kg/day) during conditioning from day –8 through day 0.  Patients who underwent transplantation between January 2006 and August 2008 were continued on L-AmB until oral antimycotic therapy was started prior to discharge (group 1).  All patients undergoing transplantation between September 2008 and June 2010 were switched to CAS starting on day 1 until oral antimycotic therapy was started prior to discharge (group 2).  The observation period was defined as the time from the start of IV antimycotic prophylaxis until three weeks after switching to oral antimycotic prophylaxis three to four days before inpatient discharge.  Patients were observed for tolerability, safety, and efficacy of caspofungin, and infection rates were compared between the two groups.

• One hundred twenty patients were included.
• Patients were younger than 18 years.  Twenty patients were younger than 6 years in the L-AmB arm and 17 were in the CAS arm; 24 patients were aged 6 to 11 years in L-AmB arm and 20 were in the CAS arm; and 16 patients were aged 12 to 18 years in the L-AmB arm and 23 were in the CAS arm.
• In the L-AmB arm, 55% of patients were male and 45% were female.  In the CAS arm, 63.3% of patients were male and 36.7% were female.
• Key disease characteristics were patients with hematologic malignancies.  Nonmalignant hematologic disorders and inborn errors of metabolism undergoing allogeneic HSCT were evaluated. The L-AmB arm included patients with acute lymphoblastic leukemia (ALL) (30%), acute myeloid leukemia (AML) (11.7%), juvenile myelomonocytic leukemia (JMML) (5%), chronic myelogenous leukemia (CML) (5%), myelodysplastic syndromes (MDS) (10%), non-Hodgkin Lymphoma (NHL) (1.7%), solid tumors (15%), aplastic anemia (1.7%), neurometabolic diseases (8.3%), immunodeficiency (6.7%), Chediak-Higashi syndrome (3.3%), and Morbus Kostmann (1.7%).  The CAS arm included patients with ALL (28.3%), AML (1.7%), JMML (3.3%), MDS (8.3%), NHL (5%), solid tumors (16.7%), aplastic anemia (16.7%), neurometabolic diseases (8.3%), and immunodeficiency (11.7%).
• In the L-AmB arm, 53.4% of patients had some degree of graft-versus-host disease; in the CAS arm, 61.9% of patients had any degree of graft-versus-host disease.

• Single site 
• Inpatient 
• University Children’s Hospital Tubingen, Germany

• Patients were undergoing the active antitumor treatment phase of care.
• The study has clinical applicability for pediatrics.

This was a single-center, retrospective study.

Biochemical laboratory results were measured.

Leukopenia was observed for a median duration of 12 days in both groups.  Median duration of therapy was 23 days (range 9–72) in group 1 (L-AmB) and 24 days (range 14–49) in group 2 (CAS).  There was no incidence of proven aspergillosis or another invasive fungal infection in either group.  No proven fungal breakthrough infections were observed in either group three weeks after the conclusion of IV fungal therapy.  No patient died of an invasive fungal infection. Clinical side effects related to treatment were observed in 8.3% of patients in group 1 and 3.3% in group 2, with four patients in the L-AmB arm being switched to CAS due to side effects.  There was a statistically significant but transient increase in alanine aminotransferase (ALT)/aspartate aminotransferase (AST) in both groups, and hypokalemia occurred significantly (p = 0.006) in the L-AmB arm (group 1).

This study retrospectively showed that the efficacy of the two antifungal agents used for prophylaxis was good with no proven invasive fungal infection noted in either group.  This could be an option to limit the side effects and potential nephrotoxicity noted in L-AmB administration.  Larger, prospective studies are needed for true recommendations.

• Risk of bias (no control group, no blinding, no random assignment, no appropriate attentional control condition)
• Findings not generalizable*

* Findings may not be generalizable to adult patients, but they could be generally applied to pediatric patients undergoing allogeneic HSCT, which is a small group.

Nursing is imperative in the monitoring and administration of medications in this setting.  The need for monitoring, especially for infusion reactions, hypokalemia, and nephrotoxicity, is higher in those receiving L-AmB.  The use of CAS may reduce this need, but nurses must still be vigilant to identify fever or other symptoms in these patients.

To explore the efficacy of itraconazole, voriconazole, and posaconazole for breakthrough fungal infections with a secondary objective of analyzing the safety and feasibility of these three different regimens in a pediatric hematopoietic stem cell transplantation (HSCT) population

This study consisted of the observation of 150 pediatric patients split into three groups between the ages of 0.6–17.7 years with hematologic malignancies undergoing allogeneic HSCT. All patients received one of the azoles as primary oral antifungal prophylaxis following HSCT. Fifty consecutive patients from 2006 to 2007 were in the itraconazole group, 50 consecutive patients from 2006 and 2010 in the voriconazole group, and 50 consecutive patients from 2010 to 2011 were in the posaconazole group when the center switched to posaconazole for prophylaxis. The observation period lasted from the start of oral prophylactic treatment till two weeks after the withdrawal of therapy.

• N = 150  
• AGE: All patients were aged less than 18 years
• MALES: 54%, FEMALES: 46%
• KEY DISEASE CHARACTERISTICS: Majority were hematological malignancies, but also included some solid tumors, neurometabolic disease, and immunodeficiency syndromes; all underwent HSCT 
• OTHER KEY SAMPLE CHARACTERISTICS: Conditioning regimens and transplant type (MUD, MMUD, MMFD, and MFD)

• SITE: Single site  
• SETTING TYPE: Inpatient    
• LOCATION: University Children’s Hospital Tübingen

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Pediatrics

Retrospective, single-center survey; one sample t-test used the Wilcoxon matched-pairs signed-rank test

• Proven probable and possible invasive fungal infections classified according to the National Institute of Allergy and Infectious Disease Mycoses Study Group
• Galactomannan antigen testing

Possible invasive fungal infections occurred in 4% of the itraconazole group, 6% of the voriconazole group, and 0% of the posaconazole group. There were no significant differences comparing all three. Adverse events occurred in 12% of the itraconazole group, 14% of the voriconazole group and 8% of the posaconazole group (no significant difference). All three groups showed a significant increase in ALT and AST as well as a significant difference between baseline and maximum levels of ALT and AST without clinical symptoms. Bilirubin also was increased during all three drug regimens but remained within the upper limits of normal. The kidney parameters (BUN/Cr) also showed an increase in all three groups but were not above reference values. Other adverse effects included hyponatremia. Cyclosporine (CsA) levels were evaluated in select patients in all three groups requiring dosage adjustments with a 12% dose reduction of CsA in the itraconazole and voriconazole group and as much as a 25% dose reduction in the posaconazole group.

Current guidelines for the use of oral antifungal prophylaxis in pediatric patients after HSCT are based on insufficient data. Despite the positive results, showing efficacy of all three drugs, it was comparable with no proven or probable fungal invasive infections. The analysis of a larger number of patients is required.

• Risk of bias (no control group)
• Risk of bias (no blinding)
• Other limitations/explanation: The majority of patient’s received IV liposomal amphotericin or IV caspofungin prior to the switch to oral monoprophylaxis, and this may have been a positive contributing factor to prevent invasive fungal infections. The interpretation that there was no significant difference in side effects – due to a few occurrences in the posaconazole arm the power was low at 16.2% – urges caution when interpreting the difference.

Because of the small number of current trials, larger trials are needed to compare each of the azoles as monoprophylaxis. Additional studies are needed to better understand the side effect profiles of the azoles and their interactions with antibiotics or immunosuppressants.