To explore effects of music and relaxation interventions on anxiety among patients with cancer and orthopedic interventions

Patients were randomly assigned to the music group, relaxation group or usual care control. Participants in the music group listened to a 20 minute CD of music composed by the hospital’s music therapist. The CD used harp and vocal music with spoken relaxation instructions. Patients in the relaxation group listened to and viewed a music video for 20 minutes that featured nature scenes and instrumental music. The control group were allowed 20 minutes of unstructured free time and were not allowed to listen to music during that time. The intervention was provided once during the first 48 hours of hospital admission. Study data were obtained immediately before and after the intervention.

• N = 112
• MEAN AGE = 60.6 years (range = 24-87 years)
• MALES: 37%, FEMALES:  63%
• KEY DISEASE CHARACTERISTICS: 49% were patients with cancer
• OTHER KEY SAMPLE CHARACTERISTICS: 59% were receiving anti-anxiety medications

• SITE: Single site  
• SETTING TYPE: Inpatient  
• LOCATION: Illinois

• PHASE OF CARE: Active antitumor treatment

• Randomized, controlled trial

• Spielberger State Trait Anxiety scale
• Blood pressure and heart rate

Although there were some differences among groups in single items on the anxiety measurement tool, there were no differences across groups for total anxiety scores. Anxiety scores declined in all on average (p < 0.001)

Results did not show effectiveness of the music and relaxation interventions used here, although anxiety did decline somewhat more in both intervention groups.

• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Unintended interventions or applicable interventions not described that would influence results
• Other limitations/explanation: Interventions were delivered via the hospital TV system, so could only be viewed at certain times. There is no description of the reason for hospitalization, so the degree to which some patients may have been in more anxiety-producing situations is unknown. There was no subgroup analysis to account for the potential impact of anti-anxiety drugs administered.

This study did not provide strong evidence supporting effectiveness of music and relaxation interventions for anxiety among the hospitalized patients involved. At the same time, there have been some studies showing benefits of music for various symptoms, and although not significant, this study did show greater reduction in anxiety with the intervention. This type of intervention is low risk and low cost, and may be beneficial to some patients. Here, the intervention was provided via the hospital television system, which can provide a very practical approach to delivery of the intervention.

Carbamazepine was tested in the prevention of chemotherapy-induced perihpheral neuropathy (CIPN) in 10 of 40 patients receiving oxaliplatin, folinic acid, and 5-FU chemotherapy. Ten patients also received carbamazapine 200 mg orally. Carbamazepine 200–600 mg was administered orally, with doses adapted to serum levels of 3-6 mg/l starting the week prior to treatment for two days, increased dose to 600 mg orally, and then doses were titrated to meet serum levels of 3-6 mg/l. Carbamazapine was administered until the end of oxaliplatin therapy, but if CIPN symptoms continued, carbamazepine also was continued until symptoms dissipated.

• A total of 40 pretreated patients with advanced colorectal cancer received combination chemotherapy with oxaliplatin 85 mg/m² on days 1, 15, and 29.
• Folic acid 500 mg/m² and 5-FU 2,000 mg/m² were given on days 1, 8, 15, 22, 29, and 36.

The study was a non-randomized pilot design.

• Weekly neurologic examinations measured vibratory sensibility of the plantar surfaces of feet and hands by a tuning fork, cold-induced symptoms, and documentation of side effects.
• Neuropathy also was assessed by the World Health Organization toxicity grading scale.

No WHO grade 2-4 neuropathy was found in the patients treated with carbamazepine compared to 30% who experienced grade 2-4 neuropathy in a historical control group.

• The study's non-randomized, non-blinded design was a limitation, as was the use of a historical comparison group.
• The very small sample size of 10 participants precludes comparison of group differences.
• Study methods and analysis were not well described.

Sample Size: 39

Age Information:  No information reported

Gender: Not reported

Diagnosis Information: Not provided

Setting Type: Single site, Outpatient setting

Location: United Kingdom

Long term followup

End of Life and Palliative Care

To examine the effects of the combination of self-hypnosis and pharmacologic pain management

Patients with cancer-related pain were randomly assigned to the order in which they received two different approaches—self-hypnosis with pain medications and pain medications alone. Patients used a daily log to record pain levels and the use of analgesics.

• N = 39
• AGE: No information reported
• MALES, FEMALES: No information reported
• KEY DISEASE CHARACTERISTICS: Not provided

• SITE: Single site
• SETTING TYPE: Outpatient setting
• LOCATION: United Kingdom

• PHASE OF CARE: Long-term follow-up, end-of-life and palliative care

• Single group crossover design
  • Randomized

• Visual analog scale
• Stanford Hypnotic Clinical Scale for Adults (for response or non-response to self-hypnosis)

Eleven patients reported achieving pain control; 12 reported benefits in relaxation, rest, and sleep; and 9 reported no impact.

The study report lacks full quantitative findings and, thus, very limited information about the efficacy of hypnosis.

• Small sample of less than 100
• No analysis of the differences between hypnosis and \"control” condition
• Those who added self-hypnosis first in the crossover sequence were likely to have contaminated results that occurred later in the control condition.
• No disease-related or other demographic information about the sample is provided. 
• Very limited reporting of results and analysis of findings

This study provides little information and no clear support for the efficacy of hypnosis for chronic cancer-related pain.

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.