To evaluate the efficacy of aprepitant in the prevention of chemotherapy-induced nausea and vomiting (CINV) for in patients with colorectal cancer receiving oxaliplatin

• N = 413 for full analysis set; however, because of either refusal of chemotherapy (10 patients) or ineligibility on review, only 370 patients were evaluated for the first cycle protocol set. The number lowered further to 338 for second cycle protocol set because of deletion of oxaliplatin from the chemotherapy regimen or lack of data (i.e., not recording in the patient diary).  
• MEAN AGE = 64.2 years
• MALES: 61%, FEMALES: 39%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Colorectal cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Oxaliplatin-based chemotherapy, adults

• SITE: Multisite
• SETTING TYPE: Hospitals
• LOCATION: Japan

PHASE OF CARE: Active anti-tumor treatment

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

Patients used a diary on days 1–6 to record the use of rescue antiemetics, severity of nausea, and episodes of vomiting. The severity of nausea was recorded on a four-grade scale. Tolerability, or other adverse effects, were monitored through laboratory tests and a physical examination.

For patients receiving oxaliplatin for the treatment of colorectal cancer, CINV prophylaxis with aprepitant or fosaprepitant significantly reduced the rate of vomiting in the acute and delayed phases and significantly reduced the rate of nausea in the delayed phase.

Aprepritant and fosaprepitant are safe and effective for the prevention of CINV in patients with colorectal cancer who receive oxaliplatin.

To see if a combination of low-dose antidepressants and antiepileptic is effective in treatment of pain from bone metastases

Patients were randomized to one of three groups: pregabalin 50 mg every 8 hours (P), pregabalin 25 mg every 8 hours and imipramine 5 mg every 12 hours (PI), or pregabalin 25 mg every 8 hours and mirtazapine 7.5 mg every 12 hours (PM). Assessments were done at baseline and daily between days 1–7 and on days 10–14.

• N = 27  
• MEAN AGE = 58 years
• AGE RANGE = 37–77 years
• MALES: 75%, FEMALES: 25%
• KEY DISEASE CHARACTERISTICS: All had confirmed bone metastases.
• OTHER KEY SAMPLE CHARACTERISTICS: Baseline pain scores were higher than 6 on scale of 0–10. Across groups, the daily opioid dose in morphine equivalents was 57.5 (range = 20–200). All patients were receiving bisphosphonates and loxoprofen.

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

• PHASE OF CARE: Late effects and survivorship
• APPLICATIONS: Palliative care

• Three-group randomized trial

• Numeric pain scale (0–10)

Total pain scores decreased significantly on day 1 in all groups (p < .05). By day 2, pain scores declined significantly more in the PI and PM groups and remained essentially stable and consistently lower than the P group (p < .05). A few patients developed dizziness and mild drowsiness. No changes were seen in electrocardiograms.

The combination of low-dose pregabalin and low-dose antidepressant significantly reduced pain in this study.

• Small sample (less than 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias(sample characteristics)
• Other limitations/explanation: The baseline daily opioid dose varied widely, and the overall average was relatively low for intractable pain. The timing of assessments varied, and only very short-term results are stated. The study did not have a control group.

Findings suggest that the combination of low-dose antidepressant and antiepileptic medication as adjuncts to opioids and bisphosphonates may improve pain control in patients with intractable pain from bone metastases. This type of combination may be worth trial in patients with this type of pain. Nurses should be aware of the potential for drug-drug interactions in patients taking multiple medications. This potential may be less with low doses, as used in this study.

To review the role of palifermin and other current and potential treatments for chemotherapy-induced mucositis in the context of pathobiology in hematologic malignancies

Database searched was MEDLINE. Abstracts and published proceedings reporting the role of palifermin in the management of mucositis were reviewed. 

Search keywords were MeSH headings for chemotherapy, cyclophosphamide, etoposide, GI mucositis, GVHD, hematology, hematological malignancies, hematopoeietic stem cell transplantation, hemorrhagic  cystitis, HSCT, keratinocyte growth factor, KGF, leukemia, lymphoma, melphalan, methotrexate, mucositis, multiple myeloma, oncohematology, oral mucositis, pain, palifermin, radiation, radiotherapy, soreness, and total parenteral nutrition.

Palifermin in standard and high dose chemotherapy

• Only case reports and one small study were included.  It was concluded that insufficient evidence exists to support palifermin use in patients without transplantation.

Palifermin in autologous stem cell transplantation

• One study in 212 patients showed that among those who developed grade 3 or 4 mucositis, the duration was shorter in those who received palifermin (p < 0.001).
• No randomized controlled trials and only a few additional small studies and case series were included.
• Insufficient evidence was found to make any recommendation regarding palifermin in these cases.

Palfiermin in graft-versus-host disease

• Two studies using palifermin were cited, but no appraisal of findings was provided. It was noted that palifermin is used in this setting, and the biological rationale and brief findings in animal models are stated.

Other interventions for management of mucositis

• Findings from meta analyses indicate that, while some interventions have some benefit, the strength of the evidence was variable, and findings in one meta-analysis reported that no single intervention was capable of completely preventing oral mucositis.
• A number of cytokines and growth factors other than palifermin were indicated that have been or are currently being investigated to treat or prevent mucositis. The mechanism of potential activity and effects seen were provided.
• Other agents outlined included chlorhexidine, povidone iodine, pilocarpine, histamine gel, benzydamine oral rinse, amifostine, systemic glutamine, nonsteroidal anti-inflammatory drugs, and oral doxepin. Evidence was deemed insufficient to determine the efficacy and role of these agents.

Control of oral mucositis pain and provision of supportive therapy and regular assessment are critical management components.

This article provided information about various approaches in the management and prevention of oral mucositis in patients with hematologic malignancies and outlined the biologic mechanism of action and observed effects from review of the literature. However, it provided little information about the actual strength of evidence and is based on a limited literature search. No clear description of rationale for article inclusion was included.

The authors concluded that evidence supports the use of palifermin, but the article stated elsewhere that evidence in this area is insufficient in some patient groups, and only one nonrandomized study is cited where the duration of high-grade mucositis was shorter in patients who received palifermin, suggesting a biased view of the role of palifermin.

This article can provide useful information regarding the mechanism of action of various treatments, but it is not helpful in determining relative effectiveness of various interventions.

To evaluate the use of plain ice, flavored ice, and standard care in the management of oral mucositis

Patients receiving 5-fluorouracil (5-FU) were randomized to receive standard care plus plain ice, standard care plus flavored ice, or standard care alone. Standard care alone consisted of mouthwashes of plain or salty water four times daily plus use of a soft toothbrush and nonabrasive toothpaste. Patients who were assigned to one of the cryotherapy arms were instructed to swirl the ice around the mouth for five minutes prior to, five minutes during, and 20 minutes after the injection. Patients who used plain ice were instructed to do so three times daily. Flavored ice was in the form of a purchased product called \"icy poles.\" Nurses assessed mucositis prior to each chemotherapy cycle and 15 days after each intervention. The sequencing of the interventions was random.

• The study reported on 79 patients across three cycles of chemotherapy.
• The majority of patients were male (67%) and had colorectal cancer (92%).

The study was conducted in an outpatient, chemotherapy, acute care setting at a teaching hospital in Australia.

This was a randomized, controlled, crossover trial.

• Investigators used an Oral Assessment Guide (OAG) and the Western Consortium Cancer Nursing Research (WCCNR) scale to assess mucositis.
• A patient questionnaire was used to gather information regarding comfort, satisfaction, and factors affecting compliance.

• Data analysis of 67 patients were provided as 12 patients were unable to complete the first intervention.
• The reported odds ratio (odds of symptoms increasing versus not increasing) were as follows.
  • Standard care versus ice: OAG 3.26, p = 0.002; WCCNR 3.23, p = 0.021
  • Standard care versus flavored ice: OAG 3.50, p = 0.003; WCCNR 4.00, p = 0.012
  • Ice versus flavored ice OAG 1.07, p = 0.872; WCCNR 1.20, p = 0.774
  • Leucovorin versus no leucovorin: 4.46, p = 0.050
• Pain scores were only available for analysis on 28 data sets because of incomplete data. Ice chips were found to be more effective than standard care in reducing pain (p = 0.009). Flavored ice did not differ from either of the other two treatments (p = 0.152, p = 0.581).
• The taste of the flavored ice and the time required to complete either form of oral cryotherapy were the two main concerns.

• Both forms of cryotherapy were effective in reducing the severity of oral mucositis after each cycle.
• The use of leucovorin appeared to increase the odds of patients experiencing mucositis at least fourfold.
• Use of crossover design is a strength of this study.

• The sample size was small.
• Only conducting oral assessment prior to chemotherapy initiation and on day 15 may not have provided a complete picture of the differences across groups.
• The study was not able to be blinded because of the nature of the intervention.

The study explored the effects of daily use of isoflavonoids on climacteric symptoms and QOL in postmenopausal women who had been treated for breast cancer.

Phytoestrogen tablets and similar-looking placebo tablets (six tablets per day) were taken every 12 hours with a glass of water. The participants were seen at the research center before and after each treatment period. Sixty-two postmenopausal, symptomatic women were randomized to use either phytoestrogen (tablets containing 114 mg of isoflavonoids) or a placebo for three months; the treatment regimens were reversed after a 2-month washout period.

Six women discontinued the trial for various reasons during the first phase. Thus, 56 women completed the study. The mean age pf participants was 54 (± 6 years).

• Inclusion criteria: breast cancer survivors (none using tamoxifen) who reported incapacitating hot flashes and other climacteric symptoms after the onset of spontaneous menopause, as seen from their high circulating levels of FSH and LH. 
• Exclusion criteria: Use of sex steroids (including tamoxifen); use of natural products with possible estrogenic activity; use of drugs possibly affecting climacteric symptoms, metabolism, or absorption of phytoestrogens (e.g., antibiotics during the previous three months); and history of any thromboembolic or hepatic event.

This was a randomized placebo-controlled crossover trial of phytoestrogens in treatment of menopause in breast cancer participants.

At each visit, the participants were interviewed about hot flashes and other typical climacteric symptoms using the Kupperman index and Menopausal Visual Analogue scale. Blood levels of phytoestrogens, FSH, LH, estradiol, and sex hormone-binding globulin, liver enzymes, and creatinine levels were followed. Compliance with treatment was confirmed by diary records and by measurement of serum phytoestrogen levels.

The use of phytoestrogens led to significant rises in the levels of phytoestrogens, whereas the placebo regimen had no effect. Kupperman indexes at the end of treatment with phytoestrogen or placebo did not differ. Hot flashes and the other components of the Kupperman index were not relieved by the phytoestrogen regimen when evaluated separately.

Pure isoflavonoids at a dose of 114 mg for three months did not relieve hot flashes or other menopausal symptoms in participants with breast cancer

Potential limitations of the trial included:

1. Study period was of short duration (three months). 
2. Possibility that phytoestrogens may trigger changes in target organs in processes requiring more than three months. It would be valuable to have long-term data on the effects of phytoestrogens.
3. Were doses physiologically suitable? Doses appeared sufficiently large, given the elevations in phytoestrogen levels in participants.

To clarify the effect of music interventions on anxiety for adult patients with cancer from rigorously conducted studies
 

TYPE OF STUDY: Meta-analysis and systematic review

• Databases searched were PubMed, PsycINFO, CINAHL, Web of Science, and the WorldCat dissertation database.
• Search keywords were music, music therapy, music intervention and cancer, neoplasm, and malignancy.
• Studies were included in the review if they
  • Were a randomized controlled trial
  • Tested a music intervention
  • Studied an adult population
  • Reported measurable anxiety outcomes
  • Used validated measures
  • Were accessible in full text
  • Scored at least 5 on the PEDro scale, indicating a high-quality study.
• Exclusion criteria were not specified.

• A total of 606 references were retrieved.
• The PEDro scale was used to evaluate quality, applied independently by two people.

• A final number of 13 studies were reviewed, with 4 included in meta-analysis.
• A total of 709 patients were included in the review, with a sample range across studies of 20–98.
• The sample had various tumor types. Most studies were done during active treatment. One study was done related to a bone marrow biopsy procedure.

Patients were undergoing active antitumor treatment.

Length of the intervention varied substantially from 5 minutes to 4 hours. There was high variability in the number of sessions delivered. Most studies examined a single intervention with immediate pre and post anxiety measurement. Three delivered live music, 1 involved a music therapist, and 11 involved listening to music via headphones. Meta-analysis showed no significant difference between the music intervention and controls (SMD = -0.003 (95% CI -0.51, 0.52).

Meta-analysis showed no significant effect of music interventions on anxiety in adults with cancer.

• A low number of studies were included in meta-analysis.
• There was high heterogeneity among the studies.
• There was variability in the type, duration, and timing of the music interventions used.

Results of this analysis do not support an effect of music interventions on anxiety in adults with cancer.

To evaluate the effects of budesonide on cabazitaxel-induced diarrhea during two treatment cycles

Patients were randomized to receiver cabazitaxel plus prednisone or cabazitaxel plus prednisone with 9 mg budesonidedaily for 44 days. Budesonide was given for the first two courses and was begun two days before chemotherapy administration. Loperamide was used for diarrhea.

• N = 227   
• MEDIAN AGE = 68 years
• AGE RANGE = 49–85 years
• MALES: 100%  
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Ninety-one percent had prior chemotherapy, and 52% had prior radiation therapy.

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

PHASE OF CARE: Active antitumor treatment

• Randomized, open-label, phase II trial

• Common Terminology Criteria for Adverse Events (CTCAE)

Among those receiving budesonide, 18% had grade 2 or 3 diarrhea, compared to 12% in the comparison group. Seven patients were hospitalized for diarrhea during treatment. No difference in diarrhea grade or prevalence existed between study groups.

Budesonide had no significant effect on the incidence or severity of diarrhea.

• Risk of bias (no blinding)
• Unintended interventions or applicable interventions not described that would influence results
• Use of loperamide was not reported

Budesonide was not shown to be effective to reduce the prevalence or severity of diarrhea among patients receiving cabazitaxel.

To investigate the dose-response relationship of topical morphine and pain in pediatric cancer patients with oral mucositis; to investigate, after topical morphine administration, the plasma levels of morphine and metabolites
 

The sample included 12 children receiving treatment for chemotherapy-induced oral mucositis. Seven patients were in the dose-response study and five were in the absorption group.

Both groups received oral morphine for pain relief. All children in the study received an oral solution containing morphine hydrochloride, 1 or 2 mg/ml, administered as a spray by means of an atomizer. The child was then to retain the solution in the mouth for 10 seconds before spitting out the solution. All children in the study also received 10‐15 mg/kg acetaminophen every 6 hours. Supplemental analgesics were allowed in the study either by patient-controlled analgesia pump or intravenously.
 

• The sample was composed of 12 patients.                         
• Mean patient age was 9 years (SD = 7 years). In the dose-relationship study, the age range of participants was 6‐15 years, with the mean age being 8 years. In the absorption study, the age range of participants was 2‐17 years, with mean age being 10.4 years.
• Of all participants, 66.6% were male and 33.3% were female.
• Diagnoses in both groups were varied and included non-Hodgkin lymphoma (NHL); neuroblastoma (NBL); hematopoietic stem cell transplantation (HSCT), including concomitant radiation therapy; and acute lymphoblastic leukemia (ALL). ALL was the most common diagnosis. The list that follows specifies diagnosis by percentage of all patients.
  • 50% (n = 6) ALL.
  • 16.6% (n = 2) NHL.
  • 25% (n = 3) NBL.
  • 8.3% (n = 1) HSCT, including concomitant radiation therapy.

• Single site
• Inpatient
• Department of Pediatrics, Copenhagen University Hospital, Sweden

• Phase of care: active treatment
• Clinical application: pediatrics

Prospective observational sequential study

• Age-appropriate 11-point pain scale, to assess pain intensity, with 0 = no pain and 10 = worst pain
• Visual analog scale (VAS), 0–10, for children older than age 8
• Wong-Baker FACES Pain Rating Scale, a VAS consisting of six faces, to assess the pain of children ages 6–8
• Face, Legs, Activity, Cry, Consolability (FLACC) Scale, composed of five behavioral components to access the pain of preverbal children age 5 and younger
• World Health Organization (WHO) Oral Mucositis Scale, on which 0 = no oral mucositis and 4 = severe oral mucositis
• Analysis of plasma and metabolites to show morphine level

In the dose-response group, the morphine mouthwash was associated with a decrease of at least 36% in the oral pain score of six of seven patients. Thirty minutes after topical doses of 0.25–0.4 mg/kg morphine, pain decreased by approximately 36%. The absorption study reported concentrations of morphine and metabolites well below effective analgesic levels; authors reported no increase in plasma concentration of morphine.

The extremely small sample size prevents applying study results to the pediatric population of patients diagnosed with oral mucositis. Further research should investigate the reliability of these findings.
 

• The study had a small sample size, with fewer than 30 patients.
• The use of a systemic opiod as a rescue medication may have caused inconsistent results.

The evidence from this study is insufficient to allow researchers to draw conclusions about the effect of topical morphine on the pain associated with oral mucositis. However, oral analgesics such as morphine could be effective supplements, causing few side effects, to established treatments. More research is needed.
 

To determine the effectiveness of laser liposuction in combination with a lymph node flap transfer on moderate upper limb lymphedema in patients with breast cancer

Patients first received a lymph node flap transfer. The lymph node flap was placed in the wrist. Laser liposuction was scheduled one to three months following the flap procedure to debulk the affected limb. Measurements were taken preoperatively and at three and six months following the procedure.

• N = 10
• MEAN AGE = 54.6 years (SD = 9.3 years, range = 35–67 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Breast cancer-related upper limb lymphedema (moderate)
• OTHER KEY SAMPLE CHARACTERISTICS: Breast cancer survivors who received modified radical mastectomies, axillary lymphadenectomy, and chemoradiotherapy

• SITE: Single site    
• SETTING TYPE: Multiple settings    
• LOCATION: Plastic and Reconstructive Surgery Department of the China Medical University Hospital in Taichung, Taiwan

• PHASE OF CARE: Late effects and survivorship
• APPLICATIONS: Palliative care 

Prospective clinical study with pre- and post-test measures

• Photography
• Serial arm measurements 
• DermaLab^® Combo device (skin tonicity) 

Six months after treatment, patients showed a reduction in arm circumference (mean = 30.5 cm, SD = 1.6 cm), which was a 90% improvement from baseline measurements. In addition, forearm circumference was reduced (mean = 27.5 cm, SD = 2.4 cm). This was a 93% improvement from baseline measurements. There was a significant reduction in arm volume from pre- to post-treatment (p > 0.01).

Combining laser liposuction with lymph node flap transfer is a novel procedure. In this study, the intervention appeared safe and reliable, and it was an effective way to significantly reduce limb volume in patients with breast cancer experiencing upper limb lymphedema.

• Small sample (< 30)
• Baseline sample/group differences of import
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment) 
• Risk of bias (no appropriate attentional control condition)
• Risk of bias (sample characteristics)
• Measurement/methods not well described
• Findings not generalizable
• Intervention expensive, impractical, or training needs

Free lymph node flap transfer and laser-assisted liposuction is very new for lymphedema treatment. This study's results were confusing, and nurses should continue observing this method. The small sample size makes it difficult to determine the extent to which this intervention would be effective for the majority of patients with upper limb lymphedema.

PURPOSE: Systematically review literature and define updated clinical practice guidelines regarding use of anti-inflammatory agents

TYPES OF PATIENTS ADDRESSED: Patients receiving chemotherapy or radiation therapy

RESOURCE TYPE: Evidence-based guideline

PROCESS OF DEVELOPMENT: Studies evaluated using Hadorn criteria and assigned levels of evidence on Somerfield criteria by independent reviewers. Findings were integrated into guidelines based on overall level of evidence for each intervention.

DATABASES USED: MEDLINE (1966–December 31, 2010)

KEYWORDS: aminosalicylic acid, amifostine, amlexanox, anti-inflammatory, anti-TNF, anti-tumor necrosis factor, aspirin, Benadryl^®, benzydamine, betamethasone, celecoxib, corticosteroid, dexamethasone, diphenhydramine, Ethyol^®, flurbiprofen, histamine, hydrocortisone, ibuprofen, indomethacin, infliximab, irsogladine, lactoferrin, mesalazine, misoprostol, N-acetylcysteine, non-steroidal anti-inflammatory agents, NSAIDS, orgotein, prednisone, prostaglandin, RK-02-02, salicylic acid, steroid, thalidomide, TNF antibody, TNF inhibitor, and tumor necrosis factor/TNF

INCLUSION CRITERIA: Articles involving anti-inflammatory agents for prevention or treatment of oral mucositis

PHASE OF CARE: Active antitumor treatment

Forty-one studies were included in the review involving use of multiple anti-inflammatory agents.

• Benzydamine mouthwash is recommended for prevention in patients with head and neck cancer receiving moderate-dose radiation therapy without concomitant chemotherapy.
• Misoprostol is not recommended for use of prevention of radiation-induced oral mucositis.
• For all other anti-inflammatory agents, no guidelines were deemed possible due to insufficient evidence.

• Most evidence reported was from studies of patients with head and neck cancer.
• Very few studies per individual agent were reviewed, and the level of evidence was low for all but benzydamine.

Two new guidelines were identified by this systemic review. The panel suggests that misoprostol mouthwash should not be used for the prevention of radiation-induced oral mucositis in patients with head and neck cancer. The other new guideline the panel recommends is benzydamine mouthwash for the prevention of oral mucositis in patients with head and neck cancer receiving moderate-dose radiation therapy (up to 50 Gy) without concomitant chemotherapy. In addition to this, the lack of clear evidence supporting the use of any anti-inflammatory agent other than benzydamine, the use of anti-inflammatory agents continues to be a promising strategy for the prevention and treatment of oral mucositis. More well-designed studies are needed to examine the use of anti-inflammatory agents for oral mucositis in various cancer care settings.