To evaluate the effect, toleration, and pharmacokinetics of dose titration of cannabis oral spray added to standard therapy to control chemotherapy-induced nausea and vomiting (CINV) in patients receiving a moderately emetogenic regimen

• Patients were eligible if they had experienced more than 24 hours of CINV despite standard antiemetic treatment after receiving one day of moderately emetogenic chemotherapy (MEC).
• Standard antiemetics included corticosteroids, 5-HT₃ antagonists, or metoclopramide.
• The Cannabis-based medicine (CBM) used was a mixture of tetrahydrocannabinol (THC) and cannabidiol 1:1 (Sativex®), with other cannabinoid derivatives, delivered in an oral spray.
• Patients were randomly assigned to the Cannabis spray (CBM) or a placebo, which was designed to match the appearance, smell, and taste of the active formula.
• On the first day of treatment, subjects received up to 3 sprays within a two-hour period following chemotherapy administration. If no signs of intoxication were seen after the first spray, a second and third were given after 30 minutes and 120 minutes.
• Patients were advised to increase home dose until day four, with up to 8 sprays within any four-hour period, every 24 hours.
• Blood samples were collected at several time points for the pharmacokinetic analysis.

• The study consisted of 16 participants.
• Median age was 50 with a range of range 34–76 years.
• The majority of participants were female (94%).
• Most patients had breast cancer.
• All patients had received one cycle of chemotherapy and were enrolled in the following cycle that included MEC agents. All had good performance status.
• Exclusion criteria were current use of illicit drugs or alcohol abuse, radiation therapy to abdomen or pelvis within one week, or cannabinoid use within 30 days prior to enrollment.

They study was conducted at multiple outpatient settings in Barcelona, Spain.

All patients were in active treatment.

This was a randomized, double-blind, placebo-controlled, parallel, phase-II trial.

Complete response was defined as no vomiting and a mean nausea score of ≤ 10 mm.

Partial response was defined as vomiting 1-4 times daily and a mean nausea score of ≤ 25 mm on a 100-mm visual analogue scale (VAS).

The following additional measurement instruments were used.

• Morrow Assessment of Nausea and Vomiting (MANE) questionnaire for frequency and duration of nausea and vomiting
• Functional Living Index-Emesis (FOIE) patient daily diary for recording of adverse events
• Daily structured telephone interview

• The mean number of daily sprays during the four days after chemotherapy was 4.81 in the CBM group, equivalent to 12.9 mg of THC.
• In the CBM group, 6 out of 7 patients tolerated dose titration. One patient discontinued treatment because of anxiety, somnolence, visual hallucinations, and confusion. These symptoms disappeared after three hours.
• Somnolence, dry mouth, and fatigue were the most common adverse events in both groups.
• In the delayed period, complete response was higher in the CBM group (71.4%) than in the placebo group (22.2%).
• In the acute period, no difference was found between the groups.
• A larger percentage of patients in the CBM group had no delayed emesis (71.4%) or nausea (57.1%) than in the placebo group (22.2%).
• Plasma concentrations showed a wide variability across subjects and suggested that patients following a repeat-administration schedule accumulate CBM active compound over time, despite the relatively short half-life of the active compounds.

The addition of this formulation of Cannabis to standard antiemetic treatment appears to improve control of delayed nausea and vomiting with MEC.

• The sample size was extremely small.
• The standard antiemetic regimen was less than what is currently recommended; however, it did follow recommendations at the time of the study.
• No discussion of the use of or need for rescue medications was provided.

• Other research has shown effectiveness of Cannabis compounds for CINV.
• The addition of Cannabis compounds to other antiemetic regimens may be specifically helpful in patients with refractory CINV, and it may be most helpful with delayed nausea and vomiting.
• The delivery system of an oral spray provides an alternative that may be helpful. Further research in the use of this formulation is warranted.

The aim of the study was to evaluate the efficacy of venlafaxine for the prevention and treatment of oxaliplatin-induced peripheral neuropathy.

Patients who reported distressing acute neurotoxicity after oxaliplatin-based chemotherapy were randomly assigned to receive either placebo or venlafaxine hydrochloride 50 mg one hour prior to chemotherapy infusion and venlafaxine extended release 37.5 mg twice daily from day 2 to day 11. Placebo was given with the same timing. From day 12 on, no venlafaxine extended release was given. Study treatment continued as long as the oxaliplatin treatment lasted. Study evaluation and data collection was conducted pretreatment, daily on day 1 through 5 of chemotherapy treatment, and at three months after study completion.

• A total of 42 patients were studied (21 women, 21 men)
• The median age was 67.4 years with a range of 32–84.4 years.
• Patients had multiple tumor types,
• Most patients were receiving FOLFOX. The median number of cycles at study inclusion was 4.5.

The study was conducted at a single outpatient setting in France.

Phase of care

• Active antitumor treatment

The study had a double blind, placebo-controlled, randomized trial design.

• Neuropathic pain symptom inventory
• Numeric rating scale for functional impairment
   

The proportion of patients reporting full relief of acute neurotoxic symptoms was 31.3% compared to 5.3% in the placebo group (p = 0.03).  In the venlafaxine group, 68.8% reported more than 50% symptom relief compared to 26.3% on placebo (p = 0.02). There were no grade 3 or 4 adverse events related to venlafaxine. Among those receiving venlafaxine, the most common adverse events were nausea and vomiting, asthenia, orthostatic hypotension, and somnolence. These side effects occurred more frequently in the venlafaxine group (p < 0.03).

The findings suggest that venlafaxine as studied here is effective in reducing acute neurotoxic symptoms associated with oxiplatin chemotherapy.

A small sample size (less than 100 participants)

The findings provide support for the efficacy of venlafaxine to prevent acute oxiplatin-related neurotoxicity. The study is limited by sample size, so the results are inconclusive. Additional research in this area is warranted.

RESOURCE TYPE: Evidence-based guideline

Over 21,000 citations were identified, 73 of which were screened. After exclusions, eight studies were included, which were published after 2009. Committee members revised the recommendations with interpretation differences resolved by consensus. Recommendations were brought before the full MASCC Antiemesis Committee. Recommendations were changed when 67% agreement was reached among the members.

• Small number of children studied
• Standard antiemetic prophylaxis differed among studies.
• Lack of standardized definition of complete response
• Lack of validated method to assess nausea
• Lack of pediatric evidence related to the prevention of CINV

Standardized pediatric CINV guidelines were developed for only the acute phase of chemotherapy administration; no guidelines exist for the anticipatory or delayed phases.

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.