STUDY PURPOSE: To provide a review of best evidence for chemotherapy-induced peripheral neuropathy (CIPN) treatments

TYPE OF STUDY: Systematic review

• FINAL NUMBER STUDIES INCLUDED = 13 
• TOTAL PATIENTS INCLUDED IN REVIEW = 685
• SAMPLE RANGE ACROSS STUDIES: 16–201

PHASE OF CARE: Active antitumor treatment

Interventions included were vitamin E, glutamine, goshajinkigan, alpha-lipoic acid, omega-3 fatty acids, acupuncture, massage therapy, acetyl L carnitine, and physical activity. All interventions showed mixed findings, with findings suggesting that acetyl L carnitine may worsen symptoms in patients receiving chemotherapy.

Limited evidence exists to show the effectiveness of integrative therapies for the prevention or treatment of CIPN.

• Limited number of studies included
• No quality evaluation
• Low sample sizes

Very limited evidence exists for effective interventions to prevent or manage CIPN. More research is needed in this area.

To determine whether pyridoxine can prevent hand-foot syndrome (HFS) in patients with cancer being treated with capecitabine

Eligible patients were randomized to receive either pyridoxine at a dose of 100 mg per day plus capecitabine-containing chemotherapy or a placebo plus capecitabine-containing chemotherapy. The placebo pills did not visually match the pyridoxine pills although they were similar. The primary investigator and the treating oncologist were blinded to treatment groups. The potency of the pyridoxine was not tested, but the drug came from multiple lots over the course of the study. Pyridoxine or placebo treatment was initiated on the first day of capecitabine treatment. Adherence was assessed by a phone call to patients during the third week of each treatment cycle as well as by pill counting. Data were collected by the treating oncologist after each cycle of chemotherapy for up to four cycles. Three topical agents that contained urea or lactic acid were not permitted to be used during the study, Aqua Care^® medicated calamine lotion (.3%), Dr. Scholl’s^® Smooth Touch deep moisturizing cream, and Dove^® moisturizing cream wash.

• N = 77  
• MEAN AGE = 54.1 years
• MALES: 38%, FEMALES: 62%
• KEY DISEASE CHARACTERISTICS: All patients were diagnosed with a cancer requiring capecitabine therapy and had never received capecitabine before.  
• OTHER KEY SAMPLE CHARACTERISTICS: Ethnicities included African American (53%), white (21%), Hispanic (18%), and Asian (7%). Inclusion criteria included age reater than 18 years old, an Eastern Cooperative Oncology Group score of 0–2, a life expectancy > 6 months, not taking vitamin B supplements, no prior HFS, no contraindication to chemotherapy, and adequate renal and liver function. Exclusion criteria included previous treatment for HFS, hypersensitivity to pyridoxine, immunosuppression or positive human immunodeficiency virusserology, and pregnancy or lactation.

• SITE: Single-site    
• SETTING TYPE: Not specified    
• LOCATION: John H. Stroger Jr. Hospital of Cook County, Chicago, IL (Hematology and Oncology Division)

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

Randomized, double-blinded, placebo-controlled trial

• The National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 3 toxicity grading criteria was used to grade HFS.

HFS developed in 26% of patients in the pyridoxine group (n = 38) and 21% patients in the placebo group (n = 39). In both groups, 16% developed grade 2 or 3 HFS. No significant differences in HFS grades were observed in the two arms of the study.

Based on a review of the study’s primary endpoints (e.g., HFS incidence, grade), there is no true benefit from using prophylactic vitamin B6 in patients with cancer receiving capecitabine-containing chemotherapy.

• Small sample (< 100)
• Risk of bias (sample characteristics)
• Key sample group differences that could influence results
• Other limitations/explanation: Low percentage of patients of Asian ethnicities; included patients who received doses of capecitabine that were lower than the standard dose, which might explain the lower incidence of HFS in the studied population

The results of this study demonstrated that administering pyridoxine (vitamin B6) to patients receiving capecitabine-containing chemotherapy did not lower the incidence or grade of HFS. Other strategies should be implemented to prevent capecitabine-induced HFS.

To identify the dosage of the liquid extract Chamomila recutita (C recutita) in mouthwash needed to reduce the incidence and intensity of oral mucositis in adult patients undergoing allogenic ​hematopoietic stem cell transplantation (HSCT)

Forty patients were randomized to one of four groups to receive routine care or routine care plus mouthwash containing a liquid extract of C recutita at .5%, 1%, or 2%. The liquid extract of C recutita was obtained at a one to one ratio by a percolation test, and the extract was standardized in 10.7 mg/mL of apigenin-7-glucoside, 20.8% w/v of dry residue, with a density of 1,002 g/mL. The final product had a pH range of 5.42–5.7, a relative density of 1.03 g/mL, and a total bacterial, fungal, and yeast count of less than 10 UFC/g. Patients receiving the intervention used the solution twice per day for one minute, one hour before breakfast and dinner beginning on the first day of conditioning and ending when oral mucosa healed or a granulocyte count exceeded 500 mm³ for three consecutive days (if a patient did not develop mucositis). Patients were instructed to spit out the solution. All patients received the standard of care, which included training for patients to brush their teeth and tongues at least three times per day and after meals, to use an extra-soft toothbrush and nonabrasive toothpaste, to remove dental devices, and to rinse with a .12% chlorhexidine solution twice per day. Data were collected daily from the start to the conclusion of the intervention period. 

• N = 40  
• MEAN AGE = 36.4 years
• MALES: 62%, FEMALES: 38%
• KEY DISEASE CHARACTERISTICS: The most frequent diseases recorded at baseline were aplastic anemia (9), acute myeloid leukemia (9) and acute lymphoblastic leukemia (8). The conditioning regimens were busulfan with cyclophosphamide, fludarabine with melphalan, and fludarabine with busulfan.
• OTHER KEY SAMPLE CHARACTERISTICS: Patients undergoing HSCT were recruited between January and August 2011 at a Brazilian cancer hospital.

• SITE: Single-site    
• SETTING TYPE: Inpatient    
• LOCATION: Brazilian Cancer Hospital

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

Randomized, phase II clinical trial

• World Health Organization (WHO) scale for oral toxicity
• Likert scale to measure tolerability of intervention (taste, smell, and color)
• Likert scale to measure nausea and vomiting

The experimental group at the 1% dosage (30%, n = 3) demonstrated a reduced incidence of oral mucositis compared to the control group (90%, n = 9; p = .01), a reduced intensity compared to the control group (p = .01), and a reduced duration of oral mucositis (intervention mean = 1.9 days, control mean = 5.7 days; p = .01). The formulation was well-tolerated by patients, and it was considered safe as no moderate to severe adverse effects were identified. Of the patients who received the 2% solution, 40% (n = 4) did not develop mucositis. Patients receiving the 1% solution had the fewest ulcerative lesions (30%), and the control group had the most (90%). In this study, 84% of patients receiving any dose of the intervention rated the solution as “pleasant” or “very pleasant” with only mild side effects reported in any group.

The use of mouthwash containing 1% C recutita extract is associated with a reduced incidence, intensity, and duration of mucositis in adult patients undergoing allogenic HSCT. Patients using the C recutita solution found it tolerable, and only minimal side effects were reported by the patients in this study.

• Small sample (< 100)
• Risk of bias (no blinding)
• Other limitations/explanation: It is unclear whether other interventions were used during this study to treat mucositis.

The findings of this study provide grounds for a phase III clinical trial involving a larger number of subjects. The results of this investigation will help nurses and other health professionals in choosing the dosage of C recutita to be used to manage oral mucositis in patients undergoing HSCT. Research is limited at this time.

STUDY PURPOSE: To assess and compare the effects of music therapy and music medicine interventions for psychological and physical outcomes in people with cancer

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 39 studies in meta-analysis, 52 studies in qualitative review
• TOTAL PATIENTS INCLUDED IN REVIEW = 3,313
• SAMPLE RANGE ACROSS STUDIES: 8–182
• KEY SAMPLE CHARACTERISTICS: Various tumor types and age groups during multiple phases of care

PHASE OF CARE: Multiple phases of care

The standard mean difference for fatigue in the music intervention group was 0.38 (7 studies, 253 participants, p = 0.03). Anxiety was reduced with music (13 studies, 1,028 patients, mean difference = –8.54, p < 0.0001). Results also showed a positive effect for depression (7 studies, 723 participants, standard mean difference = –0.4, p = 0.02).

Music interventions also had a small to moderate beneficial effect on fatigue, anxiety, and depression.

• Mostly low quality/high risk of bias studies
• High heterogeneity

Music therapy may have a small to moderate effect on fatigue, anxiety, and depression.

To examine the effects of music therapy and \"medical music\" on patients with cancer.

• Databases searched were MEDLINE, EMBASE, LILACS, CINAHL, Computer-Assisted Information Retrieval Service System (CAIRSS), and Cochrane Collaboration. The investigators also evaluated for inclusion studies listed on web sites about clinical trials or on the web sites of relevant professional organizations, those cited in journals dealing with music and music therapy, and those included in the reference lists of relevant articles.
• The investigators provided an extensive list of search terms in the report.
• Studies were included if patients, of any age, had cancer and if the studies compared music interventions to standard care, alternative interventions plus standard care, or placebo. Studies were included if they were randomized, controlled trials or incorporated quasiexperimental designs.
• Studies were excluded if they involved patients who were undergoing diagnostic procedures.

• The investigators retrieved a total of 773 studies.
• The investigators evaluated the quality of the studies according to the criteria in the Cochrane Handbook for Systematic Reviews of Interventions.

• The final number of studies analyzed was 30.
• The studies analyzed included a total of 1,891 patients.
• The range of mean patients per study was 8 to 86.
• The analyzed studies comprised multiple cancer types and age groups.

• Patients were undergoing multiple phases of care.
• The study has clinical applicability for pediatrics and palliative care.

• Findings from seven trials, regarding effect on anxiety, showed positive effects for reducing anxiety (standardized mean difference [SMD] = –0.61; 95% confidence interval [CI] [–0.97, –0.26]; p = 0.0007).
• Findings from six trials, regarding effect on pain, showed positive effects on perceived pain (SMD = –0.59; 95% CI [–0.92, –0.27]; p = 0.0003).
• The investigators noted no significant effects on depression or fatigue.
• Several studies showed that music listening and music interventions affected physical findings—for example, the studies reduced pulse rate.
• Many studies had high risks of bias, and the type, duration, and timing of the interventions varied greatly.

Music interventions appear to have beneficial effects regarding pain reduction and short-term reduction of anxiety.

• The investigators found a relatively small number of studies that examined a specific symptom or outcome.
• The interventions were very different in terms of sample types, timing, and duration; therefore, synthesizing the findings was difficult. 
• Most studies had small sample sizes and high risks of bias.

Music therapy and listening to music may be helpful means of reducing anxiety and perceived pain, and these interventions can have an effect of moderate size. The effects may be relatively short-lived, and the evidence is somewhat weak in terms of study design. However, listening to music has no risks for patients, can be easy to implement, and is an intervention that patients can do themselves. Nurses can suggest that patients use this approach to help manage pain and anxiety.

To compare the effects of dance/movement therapy to standard care and other interventions for patients with cancer.  

Databases searched were Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, PsycINFO, LILACS, Science Citation Index, CANCERLIT, International Bibliography of Theatre and Dance, ProQuest Digital Dissertations, ClinicalTrials.gov, and Current Controlled Trials National Research Register.

An extensive listing of specific search keywords per database was provided.

Studies were included in the review if they were

• Randomized, controlled trials
• Quasiexperimental designs
• Studies comparing dance/movement therapy to usual care or usual care and another intervention.

The exclusion criteria were not specified.

In total, 15 references were retrieved.

Criteria for quality evaluation from the Cochrane Handbook for Systematic Reviews was applied.  Studies were deemed to be of very low quality.

• Two studies were included in the final review.
• In total, 68 patients with breast cancer were included.

One study examined the effect of movement therapy on fatigue.  Analysis showed a stardardized mean difference (SMD) of 0.89 (95% confidence interval [CI] [0.14, 1.63]).  No strong positive findings were found for body image in patients with breast cancer in mood or distress. One study showed a moderate significant effect on quality of life (SMD = 0.89; 95% CI [0.21, 1.57]).

Findings suggested that dance therapy may be beneficial in women with breast cancer to improve fatigue and quality of life.  However, the quality of the evidence was very low, and only two small studies were found.

• The studies were of low quality.
• Only two studies were included.

Exercise has been shown to be effective in reducing fatigue in several types of patients with cancer.  Dance/movement therapy can be seen as another type of exercise that can be beneficial.

To compare the effects of music therapy and music medicine on pain and psychological outcomes, and to explore relevant patient experiences

Patients were randomly assigned to receive either two music therapy or two music medicine interventions during a two-week timeframe. After two weeks, subjects were crossed over to the other intervention. Music therapy was provided by a certified therapist and included a brief discussion of patients' concerns followed by the provision of live music based on assessed needs. Participants were invited to play an instrument, participate in breathing exercises, and express thoughts and emotions. Music medicine involved providing music based on preferences. Patients were asked not to engage in any other activity during listening. A blinded assessor interviewed patients after each music session and after the final session. Verbatim transcripts were analyzed by two coders to identify reported benefits or harms from descriptions of the experience.

• N = 31  
• MEAN AGE = 53.8 years (range = 32–88 years)
• MALES: 22.3%, FEMALES: 67.7%
• KEY DISEASE CHARACTERISTICS: Multiple tumor types with breast being most common
• OTHER KEY SAMPLE CHARACTERISTICS: 77% had high school or less education; 74.2% African American; 71% outpatient; and 29% inpatient

• SITE: Single site  
• SETTING TYPE: Multiple settings    
• LOCATION: Philadelphia, PA

• APPLICATIONS: Palliative care 

Single-blinded, randomized crossover trial

• 100 mm Visual Analog Scale (VAS) for mood and anxiety
• 11-point Numeric Rating Scale (NRS) for pain

Anxiety was reduced by 15 points with music therapy and 12 points with music medicine (p < 0.0001). There was no difference between the two conditions. Pain was reduced by 0.9–1.1 points (p < 0.0005) with no difference between the groups. Common themes from the qualitative analysis were experiencing the music as relaxing, peaceful, and soothing, and many patients appreciated the playful nature of interactive therapy sessions.

Both music therapy and listening to preferred music were associated with reductions in pain and anxiety.

• Small sample (< 100)
• Risk of bias (sample characteristics)
• Other limitations/explanation: The sample was predominantly African American. Although findings were statistically significant, the actual change in outcomes measured was small. Whether this level of change was clinically meaningful was not clear. VAS measurement for anxiety has questionable reliability. The context in which patients were involved was not stated, so there was no way to determine whether patients were in anxiety-producing situations.

Listening to music was shown to be as effective as music therapy provided by a therapist to assist in reducing pain and anxiety. Although the degree of change shown here was small and this study had several limitations, listening to music is a low-risk and simple intervention that may be beneficial to patients. Nurses should consider employing this technique with patients in anxiety-producing situations and as part of pain management.

• FINAL NUMBER STUDIES INCLUDED = 3 (2 studies included in meta-analysis)
• TOTAL PATIENTS INCLUDED IN REVIEW = 207
• SAMPLE RANGE ACROSS STUDIES: 31–139 patients
• KEY SAMPLE CHARACTERISTICS: One study conducted in Hong Kong

Two studies examined effects on depression. These were rated as having a very low quality of evidence using the GRADES system. The pooled effect of two studies showed no effect for depression. Two studies that reported anxiety showed no statistically significant effect on anxiety. Pooled results from two studies showed no support for an effect on fatigue. One study showed greater vigor with dance compared to standard care (SMD = 1.44, p = 0.0004). One study showed no significant effect for pain.

No conclusions could be drawn regarding effect of dance or movement therapy.

The quality of the evidence was very low, and two of the three trials showed a moderate risk of bias rating.

The findings of research regarding the effects of dance or movement therapy are inconclusive because of the few available studies of low quality. Additional, well-designed research to determine any potential benefits of dance versus other types of exercise and movement therapy is needed. The impact of movement as a creative art therapy is uncertain.

STUDY PURPOSE: To examine the effects of music therapy or music medicine interventions on psychological and physical outcomes in patients with cancer

STUDY TYPE: Systematic review

DATABASES USED: Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2010, Issue 10), MEDLINE, EMBASE, CINAHL, PsycINFO, LILACS, Science Citation Index, CANCERLIT, MusicTherapyWorld.net, CAIRSS, and ProQuest Digital

KEYWORDS: Music therapy, cancer, and neoplasm

INCLUSION CRITERIA:

• Randomized, controlled trials or quasi-experimental designs
• Patients diagnosed with any type of cancer
• Comparison of the music intervention with standard care alone or in combination with other treatments or placebos

EXCLUSION CRITERIA: Not specified

TOTAL REFERENCES RETRIEVED: 773

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Study quality was assessed by the authors with a scale developed and described in this study.

• FINAL NUMBER STUDIES INCLUDED = 36 (involving 30 clinical trials)
• TOTAL PATIENTS INCLUDED IN REVIEW = 1,891
• SAMPLE RANGE ACROSS STUDIES: 8–260 patients

• Distress: Two trials examined the involvement of adolescents and children in creating music videos when undergoing stem cell transplantation. The intervention was associated with a nonsignificant lower mean distress score.
• Depression: Five trials were included in a meta-analysis. The pooled estimates did not support any effects of music interventions.
• Body image: One study of 11 women with breast cancer showed that a music intervention was more effective than a cognitive behavioral intervention in improving body image.
• Mood: Pooled estimates from three trials suggest that music interventions may improve mood. Results were inconsistent.

• Pain: Seven trials compared music interventions to standard care. Five of these studies included in the meta-analysis showed a moderate effect of music on pain (standard mean difference = -0.59, 95% CI, -0.92 – -0.27, p = 0.0003).
• Respiratory rate: Two trials showed that music may reduce respiratory rate (mean difference = 2.34, 95% CI, -4.51 – -0.17, p = 0.03).
• No overall significant positive effects were seen for fatigue, physical status, blood pressure, oxygen saturation, immune function, or quality of life.

• Seventeen studies used prerecorded music, and 13 trials involved active patient participation.
• The frequency and duration of interventions varied widely, and in studies with prerecorded music, there was little description of the music was used or selected.
• A large number of the studies had a high risk of bias in the trial methodology.

To determine if glutamic acid is an effective preventative therapy in children with vincristine-associated neurotoxicity

Before the first treatment of vincristine, patients were stratified into stratum 1 or stratum 2. Stratum 1 included patients with Wilms tumor or rhabdomyosarcoma who were to receive nine weeks of vincristine; stratum 2 included patients with acute lympoblastic leukemia or non-Hodgkin lymphoma who were to receive four weeks of vincristine. Both groups were randomized to receive L-glutamic acid hydrochloride or placebo three times a day until seven days after week 4 or week 9 of vincristine. The placebo was administered in the same manner.

• N = Stratum 1: 16 placebo, 14 glutamic acid. Stratum 2: 84 placebo, 70 glutamic acid
• AGE = 3–21 years
• MALES: 52% (stratum 1), 62% (stratum 2)  
• FEMALES: 46% (stratum 1), 38% (stratum 2)  
• KEY DISEASE CHARACTERISTICS: Patients with Wilms tumor, rhabdomyosarcoma, acute lymphoblastic leukemia, or non-Hodgkin lymphoma
• OTHER KEY SAMPLE CHARACTERISTICS: All were newly diagnosed.

• SITE: Single site
• SETTING TYPE: Not stated
• LOCATION: USA

• PHASE OF CARE: Active treatment
• APPLICATIONS: Pediatrics

A randomized, placebo-controlled, double-blind trial

• Modified Balis Pediatric Scale of Peripheral Neuropathies

Patients who received glutamic acid did not have significantly less neurotoxicity symptoms compared to the placebo group. The subgroup of patients aged 13 years or older experienced more benefits from glutamic acid (0.28, p = 0.055) compared to patients younger than 13 years. Neurotoxicity rated less than 0.02 (p = 1) but was not statistically significant.

Glutamic acid is not considered an effective preventative treatment of neurotoxicities in preadolescents.

• Possible insufficient dosing of glutamic acid
• Variability in neurological exams as well as data collection
• Data were collected only for initial 5–10 weeks of therapy.
• The researchers identified a small sample size.

Glutamic acid is not recommended for the prevention of neurotoxicities in pediatric patients at this time.