To test the effectiveness of propolis as a mouthwash to reduce chemotherapy-induced oral mucositis

Patients were randomized to receive a propolis mouth rinse (30% extract) or sterile water placebo rinse. Patients were to swish 5 ml of the rinse in the mouth for 60 seconds, gargle, and expectorate. Rinses were used three times daily for seven days.

• N = 40   
• AGE = Not reported
• MALES: Not reported  
• FEMALES: Not reported
• CURRENT TREATMENT: Combination radiation and chemotherapy
• KEY DISEASE CHARACTERISTICS: Patients with head and neck cancer receiving chemotherapy and radiation therapy

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: Iran

PHASE OF CARE: Active antitumor treatment

Double-blind, randomized, controlled trial

World Health Organization (WHO) mucositis grading

By day seven, erythema, wounding, and general mucositis grades were lower in the propolis group (p < 0.006). Mucositis grades were lower in the propolis group.

The findings suggest that propolis mouth rinses may be helpful to manage oral mucositis in patients with head and neck cancer receiving chemotherapy and radiation therapy. Well designed research is needed to confirm these findings.

• Small sample (< 100)
• No demographic information was provided, and the chemotherapy regimens used were not adequately described. There is no information about other aspects of oral care that were used.

This study report has multiple flaws and provided only weak evidence of the potential effectiveness of propolis for the reduction of oral mucositis. Well designed research is needed to further evaluate the potential effects of this intervention.

To study the efficacy of aprepitant in the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy (MEC) for colorectal cancer

Patients with advanced or recurrent colorectal cancer were treated with standard MEC regimens including FOLFOX, XELOX, OR FOLFIRI and received either standard antiemetic therapy with 5-HT₃ receptor antagonist (RA) plus dexamethasone or aprepitant regimen including 5-HT₃ RA plus reduced-dose dexamethasone plus aprepitant. Patients were followed from the initiation of chemotherapy through day 5 using patient diaries to record emetic episodes, nausea, or rescue antiemetics in 24-hour intervals.

• N = 117 Japanese and Australian adults with recurrent or advanced colorectal cancer stratified based on Performance status 
• MEAN AGE = 63.48 years in standard group, 66.46 years in aprepitant group
• MALES: 56%, FEMALES: 44%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Patients with dvanced or recurrent colorectal cancer receiving MEC

• SITE: Multi-site   
• SETTING TYPE: Not specified    
• LOCATION: Japan

PHASE OF CARE: Active antitumor treatment

Multicenter, phase II, open-label, randomized, parallel, comparative study

The outcomes in both groups were analyzed using chi-squared tests for primary end points, secondary end points, and patients characteristics by treatment group. Two-sided sample t tests were used when appropriate. P < 0.05 was considered to be a statistically significant difference.

The percentage of patients with complete response in the overall phase was 79.6% in the standard group versus 79.7% in the aprepitant group. The acute phase was 94.9% complete response in both groups, and the delayed phase was 79.6% versus 79.7%. The overall incidence of adverse events were similar in both groups.

No significant differences existed between the standard treatment and aprepitant regimen in terms of complete suppression of vomiting, nausea, and time to treatment failure. This study demonstrates that aprepitant in combination with a 5-HT₃ RA and reduced dose of dexamethasone is well tolerated and effective for preventing CINV associated with MEC in patients with colorectal cancer.

The addition of aprepitant to standard antiemetic therapy for MEC in patients with colorectal cancer is well tolerated and effective for control of CINV, but the lack of significant difference suggests that the added cost of an additional medication is not warranted.

Patients were enrolled to test vitamin E as prophylaxis against chemotherapy-induced peripheral neuropathy.

Patients were randomly divided into groups assigned to receive chemotherapy treatment with (group I) or without vitamin E supplementation (group II). Group II served as control. Patients assigned to group I received alpha-tocopherol (i.e., vitamin E) orally at a dose of 300 mg per day twice daily during chemotherapy and as long as three months after chemotherapy was completed.

• The total sample consisted of 40 patients treated with six courses of cumulative cisplatin, paclitaxel, or their combination regimens for a nonmyeloid malignancy.
• The final sample size was 31.
• Exclusion criteria included a history of neuropathy, systemic diseases such as diabetes, lupus, HIV, alcohol abuse, and those who had received chemotherapy in the past.

The study had a pilot, randomized, controlled, open label with blind assessment design.

The clinical evaluation of neuropathy was based on a modified Neurologic Symptom Score (NSS) and Neurologic Disability Score (NDS). NSS selected symptoms such as weakness, numbness, or pain, scoring as present (1) or absent (0). Clinical signs (i.e., cranial nerves function; joint position, pin prick, and vibration sensation; muscle strength and deep tendon reflexes) were assessed using a modified version of NDS ranging from 0 (no deficit) to 4 (absence of function/severest deficit). Electrophysiologic examination included motor conduction of ulnar and peroneal nerves. Measures were taken at baseline and repeated after the third and sixth cycles as well as three months after cessation by the same neurologist.

Vitamin E supplementation significantly decreased the incidence of neurotoxicity, with 25% of patients receiving Vitamin E experiencing chemotherapy-induced peripheral neuropathy compared to 73.3% in the control group.

This pilot study with a small sample size and many variables assessed make achieving a statistically significant result by chance alone more likely.

Small sample size

To assess the efficacy and safety of celiac plexus neurolysis in reducing pancreatic cancer pain; to identify adverse effects and differences associated with various techniques of celiac plexus neurolysis

• Databases searched were Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Gateway, and EMBASE. In addition, investigators manually searched reference lists and the proceedings of relevant international professional groups.
• Search keywords were celiac plexus, nerve block, pancreatic cancer, and pain.
• Studies were included if they
  • Involved celiac plexus block implemented through a surgical approach or EUS.
  • Were randomized controlled trials that included a minimum follow-up of four weeks.
  • Were published in English.
  • Dealt with pain secondary to pancreatic cancer.
• Studies were excluded if they were reported in an abstract rather than a full article or if they dealt with pain due to chronic inflammation rather than pain relating to cancer of the pancreas.

The initial search retrieved 102 studies. Investigators reviewed the studies in terms of risk of bias. Investigators performed a meta-analysis on studies that they selected to include.

• The final sample of studies consisted of six studies involving 358 patients.
• Range of sample size, across studies, was 20–137.

• At four weeks, mean pain score difference according to a visual analog scale was –0.42 with 95% confidence interval (CI) –0.71 through –0.13 (p = 0.004) in favor of celiac block. At eight weeks, investigators noted significant heterogeneity.
• Opioid consumption was lower with celiac plexus block, with a mean difference at four weeks of –34.33 (95% CI –44.43 through –24.24, p < 0.00001).
• Adverse events were more likely to occur in control groups. The most common adverse events were diarrhea and constipation. These effects may have been associated with the higher opioid consumption of patients taking placebo.
• The number of studies was insufficient to allow researchers to evaluate the efficacy of different block implementations.

Celiac plexus block appears to be a safe and effective means of reducing bone pain associated with pancreatic cancer. Results show that celiac plexus block has a slight but statistically significant advantage over usual analgesic treatment. Investigators noted that the studies included in the analysis had some identified risk of bias. Three of the studies were blinded; three were not. The studies Arcidiacono et al. reviewed were the same studies that Yan and Myers reviewed in 2007.

Data are insufficient to allow researchers to evaluate the differences between CT-guided and posterior percutaneous celiac plexus block techniques.

Nurses should be aware of celiac plexus block as a means of pain management in patients with cancer of the pancreas. Nurses should advocate for the patient and inform him or her of potential treatment options. Findings of this meta-analysis are based on follow-up at four weeks, and results showed significant heterogeneity at eight weeks. This suggests that efficacy may not be sustainable over the long term. Further research, including long-term follow-up, is needed.

STUDY PURPOSE: To review the evidence for efficacy of music interventions for patients with cancer receiving palliative care and review the neurobiological evidence to explain pathways by which music may have an effect

TYPE OF STUDY: Systematic review

DATABASES USED: PubMed, CINAHL, Plus, Ovid, PsycINFO, PoQuest, and the Cochrane Library

KEYWORDS:  music; music therapy; cancer; oncology; palliative care; pain; anxiety; depression; mood; quality of life; neuroscience; endogenous opioids; dopamine; GABA; 5HT; permutations

INCLUSION CRITERIA: RCT; meta-analysis or systematic review from 1970–2012

EXCLUSION CRITERIA: Not reported

TOTAL REFERENCES RETRIEVED: Not reported

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Not reported

• FINAL NUMBER STUDIES INCLUDED = six studies regarding pain, eight studies for anxiety, four studies regarding quality of life, four studies involving effect on mood, and eight studies exploring the neurobiologic evidence
• SAMPLE RANGE ACROSS STUDIES, TOTAL PATIENTS INCLUDED IN REVIEW = 527 in pain (range: 30–136) and 410 for anxiety (range: 20–136)
• KEY SAMPLE CHARACTERISTICS: Samples included adults and children. Most interventions were done during a diagnostic or other procedure.

• PHASE OF CARE: Multiple phases of care     
• APPLICATIONS: Palliative care

In the acute pain setting, music had a moderate analgesic effect with SMD of -.059, 95% CI -0.90, -0.27 (p = .0003). Effect for chronic pain is not known and has not been well studied. The study cites results of a Cochrane review of effects of music on anxiety (SMD -11.2, p = .0088). It is noted that effect on anxiety only has been studied in the acute, situational setting. Longer-term effects and application in palliative care are unknown. Review of neurobiologic evidence suggests that music may affect specific pathways that are implicated in the pathophysiology of pain, anxiety, and depression.

Music interventions have a moderate positive effect on procedural pain and acute, situational anxiety.

• This review does not report results of the literature search nor any quality evaluation of manuscripts retrieved. 
• For pain analysis, no description is provided of methods to calculate SMD or any findings regarding heterogeneity. 
• For anxiety, this report just repeats findings from a previous Cochrane review. 
• Although inclusion criteria stated RCT, the authors did include at least one single-group trial in the review.

Music may be helpful to reduce acute anxiety and procedure-related pain. This is a simple intervention nurses could use in a variety of settings. Longer-term effects and effects in different situations are not known.

• FINAL NUMBER STUDIES INCLUDED = 10
• TOTAL PATIENTS INCLUDED IN REVIEW = 488 (62 lost to attrition)
• KEY SAMPLE CHARACTERISTICS: The frequency of intervention and type of intervention varied (Note: 10 studies of 8 different intervention foci.): 70% of the sample studies held intervention sessions once per week for a total of three to eight weeks. Participants with terminal cancer were studies either weekly or bi-weekly until death. The dance movement study held sessions two times per week for six weeks then once weekly for six weeks. One study held a music therapy session during chemotherapy.

• PHASE OF CARE: Multiple phases of care
• APPLICATIONS: Elder care

Depression and anxiety were shown to improve in three of the studies although the interventions were different (music therapy, art therapy, and mindfulness-based art therapy). Other psychological factors also improved: lower ratings of somatic symptoms in an art therapy study and a creative arts study, and psychiatric symptom improvement. Improvements in various measures of quality of life were reported in studies of mindfulness-based art therapy, art therapy, music therapy, creative arts therapy, and dance/movement therapies. Art therapy showed improvements in coping resources and mood states. Music therapy showed improvements in stress and anger. Creative arts therapy showed improvements in specific aspects of the Profile of Mood States (POMS) that were reported: tension-anxiety, depression-dejection, anger-hostility, and confusion-bewilderment.

Evidence reviewed in this study is inconclusive regarding effectiveness of various creative interventions.

• Selected articles using creative psychological interventions did not include writing therapy or drama therapy.  
• Meta-analysis was not possible, although rationale was clearly explained by the writers.
• Only one of the 10 articles was evaluated as having high quality; the remaining were satisfactory.
• Follow-up measures were not included in several studies.
• The number of articles included in the sample was small (n = 10).
• There appear to be discrepancies in accuracy of references to specific studies in the table: example, page 4, last paragraph indicates lack of replicated findings, whereas the table indicates otherwise.
• Specified Creative Psychological Interventions delivered by a qualified therapist were shown to improve well-being on several measures. 

The therapies were implemented by qualified therapists and were varied in nature, although not exhaustive of available therapies. The value of music, art, and movement therapies are shown to effectively reduce symptoms of anxiety and depression and improve quality of life, coping, and mood. Suggestions for further research are offered.

To test the hypothesis that an Acceptance and Commitment Therapy (ACT) group intervention would reduce anxiety and increase positive outcomes among cancer survivors at the re-entry phase

Groups were facilitated by a trained clinical psychologist and oncology social worker and provided in seven weekly two-hour sessions. Participants were assisted in cultivating awareness and acceptance of thoughts and emotions about cancer, disentangling from rigid thoughts and beliefs, clarifying personal values, and committing to pursue activities aligned with those values through experiential exercises, metaphors, discussion, and homework. Study outcomes were measured at 3.5, 2, and 0.5 weeks baseline prior to the intervention, midintervention, one week following the last session, and three months after the last session.

• N = 42   
• MEAN AGE = 53.52 years
• AGE RANGE = 20–70 years
• MALES: 7.1%, FEMALES: 92.9%
• CURRENT TREATMENT: Not applicable
• KEY DISEASE CHARACTERISTICS: Varied cancers; 59.5% had breast cancer. All had completed initial treatment within the past 12 months.
• OTHER KEY SAMPLE CHARACTERISTICS: Ninety-seven percent were Caucasian with an average of a bachelor’s degree and a median income of $41,000–$60,000. All patients demonstrated anxiety on screening tools, and 52% had both anxiety and depression upon study entry.

• SITE: Multi-site   
• SETTING TYPE: Other    
• LOCATION: A community center in Colorado

PHASE OF CARE: Transition phase after active treatment

Quasiexperimental

• State-Trait Anxiety Inventory (STAI)  
• Center for Epidemiological Studies Depression Scale (CESD)
• Short Form 36 Health Survey (SF-36)
• Concerns about recurrence scale
• Revised Impact of Event Scale (IES)
• Orientation to Life Questionnaire
• Participant rating of the value of each session

Anxiety declined following the intervention at immediate postmeasurement (p < 0.001) and three-month follow-up (p < 0.001). Depression symptoms also declined after the intervention (p < 0.001) and at three-month follow-up (p < 0.001). Fear of cancer recurrence decreased (p < 0.05) and at follow-up (p = 0.001).

The findings suggest that the group ACT intervention can help reduce anxiety and depression at healthcare re-entry among cancer survivors.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Measurement validity/reliability questionable
• Intervention expensive, impractical, or training needs
• Used a large battery of tests repeatedly over a short period of time—testing effect could be a threat to validity.

The group psychotherapy approach used here may be helpful to patients who are suffering from anxiety and/or depression after completion of initial treatment for cancer. Further research is needed.

To evaluate the efficacy of low-level laser therapy for prevention of chemotherapy-induced mucositis and xerostomia

Patients were randomized to receive the laser or sham procedure. The laser group had laser therapy prior to each episode of chemotherapy with a 630-nm laser with a dose of 5 J/cm². Patients in the sham control group underwent procedures with the laser unit turned off. All patients received the same instruction for ongoing oral care and underwent mucous and salivary health assessment by an oral medicine specialist prior to beginning chemotherapy, after two weeks, and then every two weeks until the end of chemotherapy treatment. Severity of pain, mucositis, and xerostomia was assessed at these times, and observers were blinded to patients’ study group assignments. Data were collected for 14 weeks.

• The study reported on 48 patients.
• The mean patient age was 45.6 years, with a range of 17-79 years.
• The sample was 50% male and 50% female.
• Cancer diagnoses were lung, lymphoma, gastrointestinal (GI), skin and breast. Patients with head and neck cancer were excluded.

This was a single-site, outpatient study conducted in Iran.

Patients were undergoing the active antitumor treatment phase of care.

This was a randomized, double-blind, sham-controlled study.

• The World Health Organization (WHO) mucositis grading was used.
• A late effects of normal tissues subjective, objective, management, and analytic (LENT-SOMA) four-point scale was used to measure xerostomia.
• A visual analog scale (VAS) was used to measure pain.

In the laser group, over the course of the study, 8.3% of patients experienced grade 2 mucositis and none experienced a higher grade of mucositis, compared to 91.6% of patients in the control group who developed grade 2 or higher mucositis (p = 0.001). By week two, xerostomia intensity was significantly lower in the laser group than the control group (p < 0.005). Across all time points, pain intensity in the laser group was significantly lower (p = 0.001). Difference in pain was substantial, with a mean of 0.7 in the laser group compared to 6.8 in the control group at week 2. The magnitude of these differences in pain intensity was large at all study assessment times.

Findings showed that provision of low-level laser treatment was effective in preventing chemotherapy-induced mucositis, xerostomia, and associated pain.

• The sample size was small with fewer than 100 patients.
• The chemotherapy agents used and the schedule given were not described. 
• Laser treatment was done prior to each chemotherapy administration, and the actual number of treatments given was not clear.
• The actual risk of mucositis development in both groups was not clear.

The results here support the effectiveness of low-level laser treatment for prevention of chemotherapy-induced mucositis. The actual number of laser treatments given was not clear. One of the difficulties in evaluating laser evidence for prevention of mucositis is the different treatment schedules and doses used in the research. Further research to identify the most effective laser dosages and schedules would be helpful to facilitate clinical translation of this evidence.

To evaluate the use of progressive muscle relaxation training in the management of nausea, vomiting, and anxiety induced by chemotherapy

The experimental group received training that consisted of tensing and releasing 16 muscle groups and breathing deeply for a total of 25 minutes. Each subject was provided with an audiotape and instructed to practice independently twice daily before meals or two hours afterward. The investigator met with the control group for 15 minutes per day to discuss concerns.

• The study consisted of 60 Japanese patients with cancer (30 subjects in the experimental group and 30 subjects in the control group) who were actively receiving chemotherapy.
• Patients' ages ranged from 21–75 years.
• Patients did not practice progressive muscle relaxation in their daily lives.

This study was conducted at a 415-bed, hospital-based cancer center in Japan.

The study was a randomized pretest, post-test control group design with repeated measures.

The Rhodes Index of Nausea and Vomiting-Form 2 (Japanese version) and the Spielberger State-Trait Anxiety Inventory were used. Reliability and validity were described in depth.

• Progressive muscle relaxation decreased the total index of nausea and vomiting scores of the experimental group.
• Index of nausea and vomiting scores for the control group increased to their highest levels 60–72 hours after chemotherapy.

Progressive muscle relaxation may contribute to a reduction in delayed nausea and vomiting. This study did confirm the usefulness of progressive muscle relaxation in decreasing the incidence of vomiting. Progressive muscle relaxation decreased subjective feelings of anxiety.

• The number, type, and dosage of chemotherapy and antiemetics were not controlled.
• Vomiting scores were very low for the experimental and control groups.
• Only one investigator conducted the study, which introduces potential investigator bias.
• The study involved only one population (Japanese patients).

To determine if low-dose gabapentin, combined with low-dose imipramine, is effective in treating cancer-related neuropathic pain

Patients were randomly assigned to one of four groups. Patients in group 1 received gabapentin 200 mg and imipramine 10 mg every 12 hours. Patients in group 2 received gabapentin 200 mg every 12 hours. Patients in group 3 received gabapentin 400 mg every 12 hours. Patients in group 4 received imipramine 10 mg every 12 hours. Pain assessment occurred at baseline and at seven days after the start of medication. Opioid rescue medication was available as needed. Nonsteroidal anti-inflammatory drugs (NSAIDs) were continued if used. No other pain medication changes were made.

• The study reported on 52 patients.
• Age range across all groups was 58–79 years.
• The sample was 52% female and 48% male.
• Patients had a variety of cancer types, including breast, lung, neck, prostate, pancreatic, gynecologic, and gastrointestinal cancers, as well as sarcoma.
• All patients had neuropathic pain. At baseline, daily opioid dose was 22.5–120 mg/day; patients were receiving either sustained-release oxycodone or fentanyl patch for pain management. All patients had inadequately controlled neuropathic pain.

• Single site
• Outpatient setting
• Japan

The study was a randomized, prospective, parallel-group trial.

Numeric rating scale (NRS), 0–10, to measure pain

Compared to baseline scores, scores relating to low-dose gabapentin-imipramine showed that the combination significantly decreased pain and daily pain episodes (p < 0.05). Compared to the other treatments, gabapentin-imipramine was the most effective (p < 0.001). The drug combination was associated with decreased doses of rescue opioids. Only the scores of the group treated with low-dose gabapentin-imipramine showed a significant reduction in pain.

The combination of low-dose gabapentin and imipramine was effective in reducing neuropathic pain.

• The study had a small sample, with fewer than 100 patients.
• Authors provided no information about analysis of differences in the use of rescue medication.
• The follow-up period was only seven days.

The use of a combination of low-dose gabapentin and imipramine, as adjuvant analgesia, can improve pain control in patients with neuropathic pain. This study demonstrates that neither of these drugs alone, in different dosages, effected the improvement. Note that this study does not establish long-term efficacy or side effects.