To assess the efficacy and safety of oral formulations of aprepitant for the prevention of chemotherapy-induced nausea and vomiting in pediatric patients aged six months to 17 years scheduled to be treated with moderately or highly emetogenic chemotherapy

Patients were randomly assigned (but stratified by age) to the aprepitant or control regimen and were divided into two age groups: less than 12 and 12–17 years. All patients received ondansetron. Patients over 12 received a 125 mg aprepitant capsule on day 1 and 80 mg on days 2 and 3 in the aprepitant arm. The control arm received a placebo daily plus ondansetron on day 1. Patients under 12 in the aprepitant arm received powder for suspension at 3 mg/kg on day 1 with ondansetron and 2 mg/kg of aprepitant on days 2 and 3. The control regimen again received a placebo daily plus Zofran on day 1. Investigators were able to add dexamethasone at their discretion with dose reductions of 50% based on adult pharmacokinetic data.

• N = 302  
• MEDIAN AGE = 7.5 years (range = six months to 17.8 years)
• MALES: 84 (55%) aprepitant group, 79 (53%) control group, FEMALES: 68 (45%) aprepitant group, 71 (47%) control group
• KEY DISEASE CHARACTERISTICS: Patients with a documented malignancy (original or relapse) who were scheduled to receive chemotherapy with at least a moderate risk of emesis and who were expected to receive ondansetron as part of their chemotherapy-induced nausea and vomiting (CINV) regimen
• OTHER KEY SAMPLE CHARACTERISTICS: Exclusion criteria: Vomiting 24 hours before day 1 of treatment, symptomatic primary or metastatic central nervous system malignancy causing nausea or vomiting, abdominal or pelvic external radiation therapy one week prior to treatment, use of antiemetics 48 hours before treatment, or any CYP3A4 substrates or inhibitors within seven days or inducers within 30 days of treatment

• SITE: Multi-site    
• SETTING TYPE: Not specified    
• LOCATION: Twenty-four countries

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

Phase 3, multicenter, randomized, double-blinded, active-comparator, controlled, parallel-group trial

• Patient diaries recorded episodes of vomiting, retching, or use of rescue medication.
• National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE v.4)
• Laboratory tests (complete blook count, chemistries, and urinalysis) and electrocardiogram

Fifty-one percent of patients in the aprepitant group achieved a complete response in the delayed phase versus 26% in the control group (p < 0.0001). The number of patients with no vomiting or rescue medication use was greater in the aprepitant group than the control group in all phases (47% versus 21% for no vomiting and 66% versus 49% for no rescue medication). The median time till the first vomiting episode was greater in the aprepitant group (96.3 hours versus 27.5 hours), and the time to first rescue medication use also was significantly longer in the aprepitant group compared to the control group. The number of patients who achieved a complete response was similar for patients aged less than 12 years receiving a powder suspension and those who received capsules. Adverse events were reported equally between groups. Serious adverse events were reported in 30% of the aprepitant group and 27% of the control group (most commonly febrile neutropenia).

A three-day age and weight adjusted oral aprepitant regimen given in combination with ondansetron with or without dexamethasone safely provided a significant benefit in preventing CINV in moderately to highly emetogenic chemotherapy in a pediatric population.

• Investigators added dexamethasone at their own discretion in a population that may have had a potential bias toward poorer outcomes and patients who may have had a greater history of emesis or more emetogenic chemotherapy.
• The study was funded by Merck and Co, Inc., who determined the study design, conduct, data collection, and analysis.

The addition of aprepitant to ondansetron with or without dexamethasone was safe and may be effective in the prevention of CINV in pediatric patients receiving moderately to highly emetogenic chemotherapy.

To evaluate the efficacy of fluconazole prophylaxis during chemotherapy-induced neutropenia.

Databases searched were MEDLINE, CancerLit, and the Pfizer company database through April 1999 (no start date was provided). The search was not restricted to the English language or published trials.

Sixteen trials were evaluated.

Studies were included if they

• Were prospective and randomized.
• Compared oral fluconazole with placebo, no treatment, or oral polyenes (nystatin, oral amphotericin B).
• Used a neutropenia definition of less than 1000/mcl and did not use intravenous (IV) antifungals.
• Reported the incidence of fungal infection.

Data from the meta-analyses reported the combined population, bone marrow transplant (BMT) recipients only, and non-BMT recipients only.

A total of 3,734 patients were evaluated. Some studies exclusively examined BMT recipients, others studied non-BMT recipients, and others evaluated a combined population.

Prophylactic fluconazole was not effective in

• Reducing fungal-related death in non-BMT recipients (although it was effective in BMT recipients).
• Reducing proven systemic fungal infections in non-BMT recipients (although it was effective in BMT recipients).

Prophylactic fluconazole was effective in

• Reducing superficial fungal infections in non-BMT and BMT recipients.
• Reducing the use of amphotericin B for persistent neutropenic fever in the BMT population (this could not be concluded for the non-BMT group).

Prophylactic fluconazole did not increase rates of proven systemic infection with resistant strains in the non-BMT or BMT populations.

Colonization of fluconazole-resistant fungi increased with prophylactic treatment in BMT recipients; however, information about non-BMT recipients is inconclusive because of lack of power and paucity of data.

To investigate the effects of low-dose aspirin on some adverse effects of gefitinib

Patients were recruited when admitted to the hospital for assessment of lung cancer. For the first two years, patients did not receive aspirin. In 2003, patients were started on aspirin 100 mg/day along with gefitinib treatment. Nonsteroidal anti-inflammatory drugs (NSAIDs) and steroids were continued in all patients.

• The study reported on 40 patients.  
• Median age was 67 years, with a range of 42–82 years.
• The sample was 60% male and 40% female.
• All patients had lung cancer, with approximately 60% having stage IV disease.
• Some patients who did not receive aspirin also were getting concurrent chemotherapy in addition to the EGFRI.

• Single site
• Inpatient setting
• Japan

Patients were undergoing active antitumor treatment.

The study was a retrospective analysis of treated versus untreated cases.

No instruments or methods were described for toxicity rating.

Overall frequency of EGFRI-related adverse events was 77.8% in those not treated with aspirin and 58.3% in those who received aspirin. Skin rash incidence was 33.3% in those on aspirin and 74.1% of those not on aspirin. There was no apparent difference in gefinitib response between groups.

Findings suggest that aspirin may help to reduce the incidence of some gefinitib toxicities, however, no clear conclusions can be made due to study limitations.

• The study had a small sample, with less than 100 participants.
• The study had baseline sample/group differences of import.
• The study had risk of bias due to lack of control group, blinding, and random assignment.
• Measurement/methods were not described.
• Definition of toxicities and skin rash were not stated, and no statistical analysis was done to determine any difference in incidence reported.
• Historical group not on aspirin was stated to also be receiving other chemotherapy, which could have affected toxicity development.
• Concomitant use of steroids and NSAIDs was stated but not described.

This study aimed to report the effects of low-dose aspirin for prevention of toxicities with gefinitib. The study does not provide strong support for this intervention; however, results suggest that further research in the use of low-dose aspirin could be beneficial.

To evaluate the effectiveness of a high-intensity (HI) and low-to-moderate–intensity (LMI) resistance and endurance exercise program compared with a wait-list control (WLC) group on physical fitness and fatigue in a mixed group of cancer survivors who completed primary cancer treatment, including chemotherapy

• N = 277  
• MEAN AGE = 50s
• MALES: 18%, FEMALES: 82%
• KEY DISEASE CHARACTERISTICS: Patients with lymphoma and breast, ovarian, colon, cervix, and testis cancer from stage I to Stage IV
• OTHER KEY SAMPLE CHARACTERISTICS: Patients who completed primary cancer treatment

• SITE: Single site    
• SETTING TYPE: Not specified    
• LOCATION: Patients recruited from nine Dutch hospitals

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

• Randomized, controlled trials including three study arms: HI exercise, LMI exercise, and WLC
• Double-blinded study

• Cardiorespiratory fitness was measured during a maximal exercise test on an electronically braked cycle ergometer.
• Upper body muscle strength was assessed using a Jamar hand-grip dynamometer.
• Fatigue was assessed using the Multidimensional Fatigue Inventory (MFI).
• Health-related quality of life (HRQOL) was measured using the European Organization Research and Treatment of Cancer Core Quality of Life (EORTC QLQ-C30)

The HI (β = 2.2, 95% confidence interval [CI] [1.2, 3.1]) and LMI (β = 1.3, 95% CI [0.3, 2.3]) groups showed significantly larger improvements in peak VO₂ compared to the WLC group. Improvement in peak VO₂ was larger for the HI group than the LMI group (β = 0.9, 95% CI [−0.1, 1.9]), but the difference was not statistically significant (p = 0.08). Relative improvements in peak VO₂ were 20% and 15% for the HI and LMI groups, respectively, which is in line with the relative improvements in healthy adults after a 12-week exercise program. No significant intervention effects were found for grip strength and 30-second chair-stand tests. Compared to the WLC group, both the HI and LMI groups showed significant improvements in general fatigue (HI: β = −1.3, 95% CI [−2.2, −0.4] and LMI: β = −1.1, 95% CI [−2, −0.2]), physical fatigue (HI: β = −2, 95% CI [−2.9, −1.1] and LMI: β = −1.4, 95% CI [−2.3, −0.5]), and reduced activity (HI: β = −1.1, 95% CI [−1.9, −0.2] and LMI: β = −1.2, 95% CI [−2.1, −0.3]), with no significant differences between both interventions. The HI group showed a beneficial effect on motivation compared to the LMI group (β = −0.8, 95% CI [−1.5, −0.03]) and WLC group (β = −1.2, 95% CI [−1.9, −0.4]), with no significant differences between the LMI and WLC groups. Furthermore, the HI group showed a significant reduction in mental fatigue compared to the WLC group (β = −0.9, 95% CI [−1.7, −0.2]). The effects on peak VO₂ were modified by age (HI: β_interaction = −0.2, 95% CI [−0.3, −0.1], p = 0 and LMI: β_interaction = −0.1, 95% CI [−0.2, −0.01], p = 0.03), indicating larger effects for younger participants. No significant interaction effects for gender or diagnosis were found for physical fitness or fatigue.

Supervised HI exercise can be safely recommended to cancer survivors shortly after their completion of cancer treatment. HI and LMI exercise were equally beneficial in counteracting general and physical fatigue.

Advising patients to exercise or referring them to exercise specialists to exercise under supervision is beneficial when possible.

To assess clinical equivalence pain at rest of 20 mg controlled-release oxycodone and 200 mg controlled-release tramadol over 24 hours

Patients were premedicated with midazolam 7.5 mg and continuous-release oxycodone 20 mg or tramadol 200 mg. Patients received the same medication 12 hours later. After surgery, patients had access to rescue medications (paracetamol [acetaminophen]). Postoperative assessments were performed at 8, 16, and 24 hours after premedication.

• The sample was composed of 53 patients.
• In the oxycodone group, mean patient age was 56.3 years; in the tramadol group, 54.9 years.
• All the patients were female.
• All patients underwent surgery for breast cancer ASA I–III.

• One site
• Inpatient
• University of Cologne, Germany

Randomized double-blinded study

• Measures of blood pressure, heart rate, respiration rate, sedation, and adverse effects
• Visual analog scale (VAS), 100 mm, to assess pain
• Measure of patient satisfaction

There was no significant difference between treatment groups with regard to adverse effects. The cumulative amount of IV paracetamol given during the first 24 hours after the operation did not differ significantly between the two groups. Postoperative pain management and patient satisfaction were equal in both groups.

There were no significant differences in pain control or incidence of adverse effects between the two groups.

• The study had a small sample size, with fewer than 100 patients.
• Pre-emptive analgesia may have confounded results.

Findings suggest effectiveness of continuous-release tramadol for the treatment of acute pain.

To evaluate the impact of the routine use of a passive disinfection cap for catheter hub decontamination

Prior to the use of disinfection caps, the organization followed Centers for Disease Control and Prevention (CDC) recommendations for catheter care and routinely used chlorhexidine-impregnated dressings. The intervention was the routine use of disinfection caps with each central venous catheter (CVC) access rather than manual scrubbing of catheter hubs. The caps were changed after each access or every seven days on high-risk units. After implementation on high-risk units for six months, disinfection caps were introduced for routine use in general oncology units. Central line–associated bloodstream infection (CLABSI) rates were compared across all phases, preimplementation to full implementation. Data were compared to that from clinical units that did not use disinfection caps.

• N = 691 patients with 806 CLABSI episodes. Total patients with central lines was not reported.
• AGE = Not provided
• MALES: Not provided, FEMALES: Not provided
• CURRENT TREATMENT: Other
• KEY DISEASE CHARACTERISTICS: Not provided
• OTHER KEY SAMPLE CHARACTERISTICS: Not provided

• SITE: Single site   
• SETTING TYPE: Inpatient    
• LOCATION: New York

• Prospective observational

• Device utilization ratio—number of catheter days to patient days
• Standardized incidence ratio—ratio of observed infections to expected number of infections, assuming incidence rates were the same as those for the reference period

No significant decrease in CLABSI rates occurred when disinfection caps were used in high-risk units. CLABSI rates declined significantly when the caps were introduced among general oncology units that were at high-risk (p < 0.001); however, CLABSI rates did not change significantly within general oncology units that were not high-risk. The proportion of contaminated blood cultures from high-risk units declined after introducing the disinfection caps (p < 0.01). Substantial cost savings with reduction in CLABSI rates and contaminated specimens was estimated, assuming hospitalwide implementation results.

The use of catheter disinfection caps may help reduce CLABSI rates in high-risk patient groups and reduce the contamination of blood culture specimens obtained via catheters.

• 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
• No patient demographic information was provided, and whether patients were being actively treated in all areas was uknown; high-risk units included general medical-surgical intensive care, not oncology-specific populations
• No information was provided on other relevant practices, such as antibiotic prophylaxis.
• Whether all catheters were long-term indwelling catheters is unclear, particularly because general intensive care units were included.
• No information regarding other factors that could influence results
• Cost reduction estimates assumed hospitalwide implementation of disinfection caps; why this was done is unclear, because changes in CLABSI rates were seen only on high-risk units.

The findings suggest that the routine use of disinfection caps for CVCs may be helpful in reducing CLABSI rates among patients undergoing hematopoietic cell transplantation (HCT) and those with hematologic malignancies deemed to be at high-risk for infection. This is a relatively low-cost intervention that may be beneficial; however, this study does not provide strong evidence in support of this effect. Given the findings here, further research on the effects of this approach is warranted.

To evaluate the efficacy and safety of thyrotropin-releasing hormone (TRH) compared with placebo to treat idiopathic cancer-related fatigue (CRF).

Patients received four study medication bolus infusions, once a week, over a four-week period. The infusions were separated by one week (plus/minus one day). Two of the infusions were TRH at doses of 0.5 and 1.5 mg (lower dose given first), and the other two infusions were placebo. Fatigue assessments were obtained at baseline.

• The sample was comprised of eight patients (one man, seven women). 
• Mean age was 58 years (SD = 9.4 years).
• Patients scored less than 34 on the Functional Assessment of Cancer Therapy–Fatigue (FACT-F) subscale and met the International Classification of Diseases, Tenth Revision (ICD-10) criteria.
• All patients were at least 18 years of age and at least one month postchemotherapy.

• Single site
• Outpatient
• University of Connecticut Health Center

Patients were undergoing the transition phase after active treatment.

The study used a pilot, phase II trial, double-blind, placebo-controlled, crossover design with two randomizations.

• Visual analog scale for energy level (VAS-E)
• Profile of Mood States (POMS) scale 
• Hospital Anxiety and Depression Scale (HADS)
• 6-minute walk test (6MWT)
• Leeds Sleep Evaluation Questionnaire (LSEQ)
• Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F)

Improvements in energy level (p = 0.004 for 0.5 mg TRH and p = 0.002 for 1.5 mg TRH), vigor and fatigue, and sleep disturbance were markedly higher for both TRH doses compared with placebo (saline infusion) throughout the interval from baseline through 72 hours postinfusion. No significant difference existed in energy level between the two doses. The walking test scores and the anxiety and depression symptoms showed no statistically significant difference between TRH and placebo. Side effects included modest increases in blood pressure, heart rate, nausea, flushing, and bladder sensation or urge to urinate.

TRH was safe and well tolerated by the patients. The results suggested significant beneficial effects of intravenous TRH in the treatment of CRF.

• The study had a small sample size, with less than 30 patients.
• The study had a risk of bias due to the sample characteristics.
• Key sample group differences could have influenced the results.
• The findings were not generalizable.
• Patient withdrawals were 10% or greater. 

More data are needed to confirm these findings with a larger population. Nurses can encourage patients with prominent fatigue symptoms to enter a clinical trial testing the efficacy of TRH.

STUDY PURPOSE: To survey literature focused on social, psychological, financial, technology, and nursing topics for evidence supporting web-based informational and supportive interventions to improve the health of the caregivers of patients with cancer

TYPE OF STUDY: Systematic review

• FINAL NUMBER STUDIES INCLUDED = 6 
• SAMPLE RANGE ACROSS STUDIES: 13–285 patients
• KEY SAMPLE CHARACTERISTICS: Greater than half were females caring for a family member with cancer; half of caregivers focused on family member with lung cancer; included studies that addressed diverse types of patient cancers (early stage to stage 4); the majority of caregivers attended some college and believed they possessed intermediate computer and Internet experience; unknown caregiver ethnicity in four of six studies 

PHASE OF CARE: Early-stage (breast cancer) to stage 4 (lung cancer)

Three of the five articles used in the systematic review showed that web-based interventions decreased caregiver negative mood. One of the three studies showed that a multifaceted CHESS intervention had a moderate effect size (d = 0.387) to decrease caregiver burden and negative mood (d = 0.436) at six months. Another study using CHESS with a clinical report showed small to moderate effect reducing caregiver negative mood at six months and at one year (d = -0.592). A third study describing an informational intervention showed a large effect size (d = 0.88) on this variable. Two multifaceted interventions and one single-faceted intervention supported lower levels of caregiver stress and perceptions of broad social support. Only two of six studies presented usability score outcomes, and only one study addressed the feasibility of the web-based intervention.

Although only six of 581 initial literacy citations met the systematic review study criteria, those six indicated the successful use of web-based cancer caregiver interventions to meet social and psychological needs. The effect sizes of the six studies compared favorably to traditional interventions focused on caregiver burden, self-efficacy, and quality of life. The limited numbers of articles on web-based interventions that positively affected diverse groups of caregivers’ social, financial, and psychological outcomes support future exploration of the usefulness and feasibility of such interventions for cancer caregiver health.

Studies showing significant effects of web-based cancer caregiver interventions may appear more often in the literature to affect article capturing for this systematic review. The lack of identification of caregiver ethnicity in 80% of the cited studies leaves a gap in understanding how non-Caucasian samples or male caregivers may respond to web-based interventions. Published studies after February 1, 2014 were absent from the review. Only six studies met the criteria for the review.

Increasing the use and success of technology to deliver health-related consumer interventions currently support initial evidence for web-based programs, aligned with traditional cancer care, to improve quality of life of patients with cancer and their caregivers. Additional research identify the dosing of Internet interventions and evidence of the efficacy of various forms of interventions is needed.

To evaluate the optimal application time for pegfilgrastim in autologous hematopoietic stem cell transplant (AHSCT) recipients.

Within two institutions, patients were assigned to either receive pefilgrastim 6 mg subcutaneously on day 1 (Peg1) or pegfilgrastim 6 mg subcutaneously on day 4 (Peg4). Primary study endpoint was time between transplant and neutrophil recovery to greater than 500/µl.  A difference of less than 1 day was not considered clinically significant.

• Fifty-three patients (45.3% male, 54.7% female) were included.      
• Mean age was 56.5 years (range 25–69).
• The most common diagnosis was multiple myeloma.  
• Most patients received high-dose melphalan.

• Multi-site  
• Inpatient

Patients were undergoing the active antitumor treatment phase of care.  

This was an open-label, phase II study.

• Neutrophil engraftment >500 µl
• Granulocyte greater than1,000 µl
• Platelet recovery greater than 20,00 and greater than 50,000 Gpt/l
• Incidence and duration of neutropenic fever
• Incidence and duration of intravenous (IV) antibiotics
• Transfusion requirement

Both groups had a median of 10 days to neutrophil engraftment >500 µl and granulocyte engraftment greater than 1,000 µl, with no difference between groups.  There were no differences between groups in time to platelet engraftment, incidence of febrile neutropenia, incidence or duration of IV antibiotics, or transfusion requirements.

 Early administration of pegfilgrastim demonstrated no benefit versus administration on day 4 after AHSCT. No clear recommendation can be made with respect to an optimal time for pegfilgrastim use.

• Small sample (<100)
• Risk of bias (no blinding)

The study findings suggest that early and late administration of pegfilgrastim are equally effective in terms of time to neutrophil, granulocyte, and platelet recovery after AHSCT, need for IV antibiotics, transfusion, and incidence of febrile neutropenia.

RESOURCE TYPE: Expert opinion  

PROCESS OF DEVELOPMENT: Clinical review

This article provides an overview of the mechanisms of action of immune checkpoint blockade and clinical effects in metastatic melanoma. The focus is the adverse effect profile and therapeutic management. The side effect profile includes a review of a meta-analysis of 1,265 patients from 22 clinical trials who received ipilimumab. Eighty-two to ninety-five percent of patients experienced treatment-related side effects. Incidence tables are provided as well as a checklist for important questions during patient visits, blood test recommendations, and organ-specific side effects. Diarrhea and colitis are described with a table of trade, treatment, and follow-up. Other organ-specific side effects are also reviewed. Recommendations for management algorithms are discussed.

Comprehensive clinical studies have shown a major benefit of anti-CTLA-4 antibody ipilimumab and two anti-PD-1 antibodies nivolumab and pembrolizumab in various tumors, including melanoma. These agents enhance an autoimmune phenomenon that affects various organs. Persistent diarrhea and colitis are evidenced early in treatment and can be serious adverse effects. The clinical significance is the debilitating effect they have on patients, with electrolyte disturbances and protracted weight loss. Intestinal perforation is a serious risk. Grade 1–2 diarrhea is treated with loperamide and electrolyte replacement. An endoscopy should be considered with persistent low-grade diarrhea because it diagnoses the true extent of the colitis. For grade 3–4 diarrhea/colitis, immunotherapy should be discontinued and high-dose corticosteroids initiated. Symptoms improve markedly with this regimen. Treatment with infliximab (5 mg/kg) is used in rare cases in which steroids do not induce a response. Colitis is associated with ocular inflammation, and observing for this side effect is imperative. Comprehensive study data identify that the timely and consistent use of corticosteroids allows for control and regression of symptoms in the majority of cases.

This is an overview of a complex multidisciplinary side-effect management concern with new checkpoint inhibitors. Further study would be necessary for a nurse to acquire in-depth knowledge for patient care.

Immuno-oncology is becoming a mainstay of pharmacological cancer treatment. Knowledge of side effects of these checkpoint inhibitors, especially diarrhea and colitis, is essential to their prevention, treatment, and management. Early recognition and intervention can reduce sequelae for patients.