RESOURCE TYPE: Evidence-based guideline

Best approach to control ANV is to control acute and delayed nausea and vomiting (level of evidence: MASCC moderate, high consensus; ESMO: III, grade of recommendation A). Benzodiazepines can reduce the occurrence of ANV (level of evidence: MASCC moderate, moderate consensus; ESMO: II, grade of recommendation A). Behavioral therapies (progressive muscle relaxation training, systematic desensitization, and hypnosis) (level of evidence: MASCC moderate, moderate consensus; ESMO: II, grade of recommendation B).

Limitation of the pediatric studies; the behavioral therapies methods applied in the studies differ in their methods.

The best approach to controlling ANV is by controlling acute and delayed nausea and vomiting. Some pharmaceutical and non-pharmaceutical treatment modalities are used for the prevention and treatment of ANV.

Table of antiemetic recommendations and strength of evidence of recommendations

1. Children ≥ 12 years, high emetogenicity, no known interaction with aprepitant-ondansetron or granisetron and dexamethasone and aprepitant, if interaction with aprepitant–ondansetron or granisetron and dexamethasone 
2. Children < 12 years, high emetogenicity: Ondansetron or granisetron and dexamethasone
3. No age restriction, moderate emetogenicity: Ondansetron or granisetron and dexamethasone
4. No age restriction, low emetogenicity: Ondansetron or granisetron
5. No age restriction,  minimal emetogenic risk: No routine prophylaxis
6. Aprepitant should be restricted to children 12 years of age and older who are about to receive highly emetogenic chemotherapy, which is not known to interact with aprepitant. There is no evidence to support the safe and effective use of aprepitant in younger children.
7. Aprepitant dose recommendations: Day 1, 125 mg PO x 1; Days 2 and 3, 80 mg PO once daily
8. Chlorpromazine dose recommendations: 0.5 mg/kg/dose IV q6h
9. Dexamethasone dose recommendations: ≤ 0.6 m2, 2 mg/dose IV/PO q12h; > 0.6 m2, 4 mg/dose IV/PO q12h. If given concurrently with aprepitant, reduce dexamethasone dose by half. 
10. Granisetron dose recommendations: High emetogenicity, 40 mcg/kg/dose IV as a single daily dose; moderate emetogenicity, 40 mcg/kg/dose IV as a single daily dose; low emetogenicity, 40 mcg/kg/dose IV as a single daily dose 
11. Metoclopramide dose recommendations: Moderate emetogenicity, 1 mg/kg/dose IV pretherapy x 1 and then 0.0375 mg/kg/dose PO q6h. Give diphenhydramine or benztropine concurrently. 
12. Ondansetron dose recommendations: High emetogenicity, 5 mg/m2/dose (0.15 mg/kg/dose) IV/PO pretherapy x 1 and then q8h; moderate emetogenicity, 5 mg/m2/dose (0.15 mg/kg/dose, maximum 8 mg/dose) IV/PO pre-therapy x 1 and then q12h; low emetogenicity, 10 mg/m2/dose (0.3 mg/kg/dose, maximum 16 mg/dose IV or 24 mg/dose PO) pretherapy x 1   

Limited evidence exists for the prevention of CINV in pediatric populations making conclusions and guidelines difficult to establish.

When managing acute CINV in pediatric patients, nurses can make informed decisions by consulting evidence-based guidelines.

PURPOSE: To provide evidence to optimize the control of anticipatory chemotherapy-induced nausea and vomiting (CINV) in children receiving chemotherapy

TYPES OF PATIENTS ADDRESSED: Pediatric patients

• DATABASES USED: MEDLINE, EMBASE, Cochrane collaboration, AMED, CINAHL, ProQuest Dissertation Abstracts, and Health and Psychosocial Instruments
• KEYWORDS: Appendices were provided for detailed search terms per database.
• INCLUSION CRITERIA: Full-text publication, evaluated an intervention for anticipatory CINV, and patients per study arm were at least 10 cases
• EXCLUSION CRITERIA: Language other than English

693 practice guideline publications were retrieved. Nine guidelines were included and scored, including those from the American Society of Clinical Oncology, Multinational Association of Supportive Care in Cancer, European Society for Medical Oncology, and National Comprehensive Cancer Network. None were directly adapted because they were aimed at adult patients. 1,586 references were retrieved from database searches, and 11 studies met the inclusion criteria.

• Control of acute and delayed CINV should be optimized to minimize the risk of developing anticipatory CINV.
• Psychological interventions such as hypnosis or desensitization may be offered to children.
• Lorazepam at 0.04–0.08 mg/kg at bedtime the night before chemotherapy and once the next day prior to chemotherapy administration may be used for prevention or treatment.

Evidence was weak, and the optimal dosing of medications for pediatric patients was not clear.

The strongest recommendation for anticipatory CINV was prevention, which necessitated maximum prevention and control of CINV when first initiated. Although newer antiemetics improved CINV outcomes, anticipatory nausea remains a problem. In general, the timeframe for evaluating anticipatory CINV is prior to the first chemotherapy administration although it also may occur daily with multiday treatment. The authors pointed to evidence from longitudinal studies that with administration of 5HT3 and dexamethasone, about a third of adults had anticipatory nausea and 6%–11% had anticipatory vomiting. Maximum CINV control initially needs to be the goal, and patients should be evaluated on an ongoing basis for anticipatory nausea prior to each chemotherapy administration as part of the assessment of adequate CINV control. More studies of pediatric patients for CINV are needed.

STUDY PURPOSE: To examine the effects of behavioral techniques (e.g., behavioral therapy, cognitive therapy, mind-body and relaxation techniques, counseling, social support, hypnosis, biofeedback, exercise, physical exercise (PhysEx), aerobic exercise, physical activity, motor activity) on psychosocial functioning outcome measures, such as fatigue, depression, anxiety, body image, and stress, and on health-related quality of life

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED =  56 studies: 39 studies of behavioral techniques; 14 studies of physical exercise; 3 studies of both 
• TOTAL PATIENTS INCLUDED IN REVIEW = Not reported. This meta-analysis reported the number of patients by each randomized, controlled trial: 5,462 (behavioral intervention patients), 1,457 (PhysEx patients), 6,919 (total)
• SAMPLE RANGE ACROSS STUDIES: 28–558 (behavioral intervention), 22–242 (PhysEx)
• KEY SAMPLE CHARACTERISTICS: 33 studies of patients with nonmetastatic cancer, 4 studies of patients with metastatic cancer, 5 studies with a mix of patients

PHASE OF CARE: Multiple phases of care
 
APPLICATIONS: Elder care, palliative care

Behavioral techniques affect specific aspects of psychosocial functioning but have a minor, insignificant effect on health-related quality of life. PhysEx has a positive effect on health-related quality of life. Behavioral techniques demonstrated a moderately significant effect on anxiety and depression and showed a significant but small effect on fatigue. PhysEx was effective for fatigue and showed a positive effect for depression.

• No quality evaluation
• High heterogeneity
• The variety of behavioral interventions made it challenging to select which was more effective than others (e.g., telephone counseling, telephone support, education, body-mind social support self-help, therapeutic groups by telephone, nurse self-efficacy).
• Studies were included only through 2008—more recent evidence has shown some different findings.
• High heterogeneity in behavioral technique analysis
• The studies used a wide range of different measurements and interventions.

A range of behavioral techniques may be effective for patients with breast cancer and fatigue, depression, and depressed body image. PhysEx was shown to improve health-related quality of life, fatigue, anxiety, and depression. Recognizing the symptoms of patients with breast cancer was emphasized as having positive effects (e.g., feeling relieved, hearing helpful strategies addressing quality of life and psychosocial problems).

To evaluate the effects of cognitive behavioral therapy (CBT) and physical exercise (PE) for management of menopausal symptoms

Patients were randomized into four groups: wait list control, CBT alone, PE alone, or combined CBT and PE. The CBT interventions consisted of six weekly group sessions focusing on hot flashes and night sweats as well as other symptoms, with a booster session six weeks after completion of the program. The PE intervention was a 12-week individually tailored program of 2.5–3 weeks exercise of a type selected by the patient with assistance of a physiotherapist. Women were provided with heart rate monitors and instructed to achieve target hear rates. In weeks 4 and 8, women were contacted by phone for any need to adjust the program. Women in the combined group received both interventions concurrently. Study data were obtained at baseline, at 12 weeks, and six months later.

• N = 352 at 12 weeks and 340 at six months  
• MEAN AGE = 48.2 years (SD = 5.6 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: All had breast cancer; 85.5% were on hormonal therapy; 81.3% were more than one year since completion of chemotherapy.
• OTHER KEY SAMPLE CHARACTERISTICS: 76% were employed full-time or part-time; 52.6% had high school education, and 38.2% had some college education. Subjects had an average of six hot flash episodes per day.

• SITE: Multi-site
• SETTING TYPE: Outpatient
• LOCATION: Netherlands

• PHASE OF CARE: Transition phase after active treatment

Randomized controlled trial

• Functional Assessment of Cancer Therapy-Endocrine Symptoms (FACT-ES)
• Hot flush rating scale
• European Organization for Research and Treatment of Cancer-Breast Cancer Questionnaire (EORTC-Breast)
• Breast cancer quality-of-life scale
• Short Form Health Survey (36-Item)
• Hospital anxiety and depression scale

Overall effects showed group differences in hot flash symptoms (p < .001) and perceived burden of hot flashes and night sweats (p < .001), but not for the frequency of these symptoms. Effect sizes for study groups were 0.4 for CBT (p < 0.001), 0.31 for PE (p = .007), and 0.36 for the combined intervention (p = .001). Perceived problem rating was only seen in the CBT groups compared to controls at both 12 weeks and six months (p < 0.001). These effect sizes ranged from 0.39 to 0.56. Fifty eight percent of the CBT group were deemed noncompliant, as were 64% of the PE group and 70% of the combined intervention group. To be deemed compliant, subjects had to attend at least four of six CBT sessions and have a minimum of 25 PE training sessions with a specified level of caloric expenditure.

Both physical exercise and CBT interventions were associated with reduced hot flash symptoms, though not the frequency of those symptoms. CBT was helpful to reduce the degree to which patients perceived hot flashes as a problem. Adherence to these programs was low.

• Risk of bias from no blinding
• Risk of bias from no appropriate attentional control condition
• Key sample group differences that could influence results
• Measurement/methods not well described 
• Other limitations/explanation: High rate of lack of adherence to the programs evaluated suggests that final analysis was underpowered and that the programs examined here may not be practical for many patients. Method of determining compliance with exercise is not described. Method of intention-to-treat analysis was not described, so it is not clear if this could have resulted in over or under estimation of effects. There was no subgroup analysis between those who were and were not compliant. Final sample analyzed was underpowered by author analysis.

Findings suggest that both CBT and PE can be helpful in managing hot flash symptoms in women with breast cancer. CBT appears to be more helpful in assisting women to reduce the perceived level of problem created by the symptom. Participation in scheduled group sessions appeared to be difficult for subjects in this study, and many were currently employed, suggesting that this approach may not be practical for many patients. Alternative methods of delivery to achieve results that are practical for patients need to be explored.

To investigate the results of a Living With Hope Program on rural female caregivers‘ self-efficacy, hope, quality of life, and loss and grief when caring for persons with advanced cancer

Components of the Living With Hope Program included caregiver viewing of a Living With Hope video and journaling centered on “Stories of the Present” over a two-week period. Journaling focused on caregiving challenges and experiences supportive of hope in the caregiving experience. Measures assessing caregiver demographic data, hope, self-efficacy, quality of life, grief, and journaling time were collected at baseline, one week, two weeks, and 3, 6, and 12 months. Trained RNs collected baseline and one- and two-week data in caregiver homes and then by telephone at 3, 6, and 12 months. Convenience sampling produced an initial N of 36 but because of attrition based on uncontrolled factors dropped to 22 by the 12-month measurement time.

• N = 22  
• MEAN AGE = 59 years (SD = 11.6 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Family members had a variety of cancer diagnoses requiring referral or receipt of palliative care services.
• OTHER KEY SAMPLE CHARACTERISTICS: 86.1% of caregivers were spouses, and half did not have caregiving assistance or services beyond palliative home care for their family member with advanced cancer; mean length of caregiving was 32.41 months (SD = 32.58 months)

• SITE: Multi-site
• SETTING TYPE: Home
• LOCATION: Rural-dwelling caregivers in Saskatchewan and Alberta, Canada

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

• A time-series, embedded, mixed methods design
  • Quantitative and qualitative

• Herth Hope Index (HHI)—measured caregiver temporality and future, positive readiness and expectancy, and interconnectedness; high test-retest reliability and validity (concurrent, criterion, and divergent)
• General Self-Efficacy Scale (GSES)—measured caregiver self-efficacy; reliable and valid measure supports history of use in many populations
• Short Form 12 (SF-12v2)—measured caregiver physical and mental health; correlates well with the longer SF-36 instrument
• Non-Death Revised Grief Experience Inventory (NDRGEI)—measured caregiver grief unrelated to patient’s death; measured existential concerns, tension and guilt, physical distress, and depression; established reliability with use in prior caregiver studies 

HHI scores at day 7 and 14 were significantly higher than baseline values (p = 0.013), and GSES scores were significantly higher at all data points compared to baseline values (p < 0.04). SF-12v2 physical summary scores were significantly lower at 12 months than at baseline (p = 0.04), but instrument mental scores at 3 and 12 months were significantly higher than at baseline (p < 0.03). A positive correlation between GSES and HHI scores (p < 0.001) and a negative correlation between NDRGEI and HHI scores (p = .0.01) was found. HHI and NDRGEI scores significantly predicted caregiver mental health summary scores (p = 0.01 or less) and similar physical health scores (p < 0.04). All caregivers completed the Living With Hope intervention with a mean 4.18 (SD = 4.07) journal entries per week and an average journal composition time of 9.12 minutes (SD = 8.89 minutes). Qualitative analysis data supported the value of journaling, social support, and faith and spirituality in responding to caregiver challenges with accessing care, financial issues, and caregiver health.

Study findings suggest that the Living With Hope Program may increase hope in rural female caregivers of people with advanced cancer who are receiving palliative care services. The study's small sample size, convenience sample, limited journaling exercise, and inherent threats to internal validity (e.g., history, selection,  maturation) due to study design support further studies of the Living With Hope Program as an evidence-based psychosocial intervention for caregivers of patients with advanced cancer.

• Small sample (less than 30)
• Risk of bias (no control group)
• Risk of bias (no random assignment)
• Findings not generalizable
• Subject withdrawals 10% or greater

Clinicians benefit from examining interventions, such as the Living With Hope Program, that improve caregiver hope via increasing self-efficacy and minimizing feelings of loss and grief with advanced cancer family member care. Study results that rural caregivers experience poorer physical and mental health than the general population also support clinician attention to caregiver health issues during care encounters.

To determine if a 5HT3 receptor antagonist and aprepitant, an NK1 antagonist, without a corticosteroid were effective in reducing vomiting in pediatric patients with brain tumors receiving highly emetogenic chemotherapy (HEC)

This retrospective chart review investigated all patients (young adults and children) receiving the medulloblastoma protocol who were prescribed a 5HT3 antagonist plus aprepitant without a corticosteroid during their first course of HEC from September 9, 2003 to March 12, 2010. All cases were matched with two controls who received 5HT3 plus a corticosteroid.

• N = 52  
• MEDIAN AGE = 13 years (range = 10–21 years)
• MALES: 32, FEMALES: 20
• KEY DISEASE CHARACTERISTICS: Patients with medulloblastoma; high- and average-risk patients included

• SITE: Not stated
• SETTING TYPE: Outpatient    
• LOCATION: Unclear

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Pediatrics and palliative care 

Single-institution retrospective chart review

• Demographics, chemotherapy regimen, and medications were pulled from charts.

The control group experienced grade 2 or higher chemotherapy-induced vomiting when compared to aprepitant recipients. When controlling for variables such as risk, age, and gender, patients who did not receive aprepitant were significantly more likely to have grade 2 or higher vomiting during the first course of HEC than aprepitant recipients.

• Small sample (< 100)

There is limited literature documenting chemotherapy-induced nausea and vomiting among pediatric patients, and this study provides helpful information to investigate the role of aprepitant. Prospective studies including patient-reported outcomes would be helpful in characterizing the benefits of aprepitant. The ability to better control chemotherapy-induced nausea and vomiting without the use of steroids is very beneficial.

To measure the efficacy of relaxation training for hospitalized patients with advanced cancer.

Patients were randomized to receive an immediate or delayed intervention, on day 3 or day 6 of a nine-day study period. The intervention was a one-hour training session delivered by a specially trained registered nurse (RN) in deep breathing and somatic tension release, as well as instruction on maintaining a state of somatic relaxation. Patients were given a CD of the audio training to repeat at night after the training.

• The sample was comprised of 18 patients (33% male, 66% female).
• Mean age was 61 years (standard deviation [SD] = 15 years) in the intervention group and 66 (SD = 12 years) in the delayed intervention group.
• Patients were hospitalized with advanced metastatic cancer, with a life expectancy of less than six months, a diagnosed sleep disorder, and fairly well-controlled pain and dyspnea.
• Multiple cancer diagnoses were included.
• Patients were hospitalized for at least five days.
• Patients had a Mini-Mental State Examination (MMSE) score of 20 or greater.
• Patients spoke French.

• Single site
• Inpatient
• Switzerland

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

This was a pilot, randomized, controlled trial.

• Numerical Rating Scale of 1 to 10
• Sleep diary
• Hospital Anxiety and Depression Scale (HADS)

Only 11 patients were able to complete the treatment phase of the study. Both groups improved (not statistically) between the day of inclusion and day 2 of therapy. No improvement occurred between days 2 and 5, which was when the intervention occurred for half of the patients. No change occurred in the use of benzodiazepines during the nine-day study.

The study did not show that a simple relaxation therapy intervention improved satisfaction with sleep in patients with advanced cancer hospitalized on a palliative care unit.

Assessment and management of sleep disturbances should be integrated into patient care early in the disease process.  Further work is needed to identify and test interventions that can be used to improve sleep in patients with advanced cancer. Further work is also needed to determine whether relaxation therapies have an effect on sleep satisfaction.

• The study had a small sample size.  
• The study had risks of bias due to no blinding and no appropriate attentional control condition.
• Unintended interventions or applicable interventions not described would have influenced the results.
• Measurements/methods were not well described.
• Measurement validity/reliability was questionable.

It is critical to assess and manage sleep disturbances in patients with cancer early in the disease process. Ongoing evaluation and research is required into effective interventions to promote sleep in patients with cancer; specifically, further work is needed to look at relaxation therapies and determine if they are effective and a means of improving patient satisfaction with sleep.

To compare the effects of Comprehensive Health Enhancement Support System (CHESS) access intervention versus provision of internet with recommended websites for lung care cancer care on informal caregivers’ burden, disruptiveness, and mood

Patients and their caregivers were provided with laptops with internet that allowed access to CHESS. CHESS is a home-based e-health system that helps users to appraise the controllability of cancer-related stressors and improves their cognitive, behavioral, and supportive coping skills by providing them with a variety of information, communication, and coaching services appropriate for cancer caregivers based on their need and preference. CHESS allows sharing critical information with clinicians via Clinician Report, where caregivers are able to communicate their needs, ask questions, and rate patients’ symptoms on a scale of 0–10. A score of 7 or more triggers an email alert to the patient’s treating clinician so he or she is aware of the patient’s and caregiver’s situation on the next patient visit. Patients randomly were assigned to internet use only or CHESS plus internet use. Internet users were provided with internet access and a list of high-quality websites for information.

• N = 246 (122 in the control [internet] group and 124 in the intervention [CHESS] group)
• AGE RANGE = 18–84 years
• MEAN AGE = 55.56 years
• MALES: 31.7%, FEMALES: 68.3%
• KEY DISEASE CHARACTERISTICS: Patients with advanced non-small lung cancer IIIA, IIIB, and IV with a life expectancy no less than four months
• OTHER KEY SAMPLE CHARACTERISTICS: English-speaking adults who are primary caregivers; participants were primarily females (68.3 %), spouses/partners (72%), and highly-educated (53% had an associate's degree); most patients had advanced disease (IV) (66.4%) and other major diseases (57.7%)

• SITE: Multi-site    
• SETTING TYPE: Outpatient    
• LOCATION: Northeastern, Midwestern, and Southwestern United States

• PHASE OF CARE: Multiple phases of care
• APPLICATIONS: Pediatrics, elder care, palliative care 

• Randomized clinical trial with a randomization ratio of 1:1
  • Participants were stratified by study site, caregiver’s race, and relationship to patient.
  • Measurements were administered at pretest and post-tests every two months up to two years, or 13 months after a patient’s death, whichever came first.
  • Analysis involved data from the first eight months only.

• Caregivers’ demographics
• CHESS use (number of logins, number of pages viewed, and time spent on the CHESS system)
• Disruptiveness was measured by the Caregiver Quality of Life-Cancer Scale (CQOLC) Disruptiveness Subscale.
• Burden was measured by the CQOLC Burden Subscale.
• Negative mood was measured by a 16-item subset of the Short Version Profile of Mood States (SV-POMS) focusing on measurement of Tension-Anxiety, Anger-Hostility, and Depression-Dejection.
• Patient symptom distress was measured by the caregiver’s perception of the patient’s symptom distress using the Edmonton Symptom Assessment Scale (ESAS).

Average use of CHESS among the intervention group was 14.6 logins, averaging browsing 293 pages and spending 177 minutes on the system (almost 50 minutes monthly). Statistically significant improvement was seen in the intervention group over the control group at six months follow-up in burden (p = .02) and negative mood (p = .006), but not in disruptiveness. These effects persisted even when patient symptom distress (on the ESAS) and other covariates were controlled. Analyses also show that these significant differences existed only at six-month follow-up, not at any other times. 

Targeted electronic systems that are designed comprehensively to help caregivers can improve their experience of caregiving by minimizing their perceived burden and improving their mood.

• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Intervention expensive, impractical, or training needs
• Subject withdrawals/attrition 10% or greater
• Physician consent was needed first before a candidate could be admitted into the study because the intervention required a clinician’s responsiveness to patients’ and caregivers’ needs. 
• Although training was given to participants who needed training on accessing CHESS and the internet, the study does limit participation of those who may not be computer savvy or would prefer receiving support in means other than electronic.

Targeted e-health systems are more likely to be beneficial to caregivers of patients with cancer when they are self-directed and have a comprehensive approach to caregivers’ needs (e.g., information, communication, coaching, interaction with healthcare providers). The benefits of e-health vary among cancer caregivers and depend on how they use the tools offered by such systems. Which feature or combination of features would be most helpful to this group of caregivers remains to be determined.

• 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.