To compare efficacy of two dosing schedules of palonosetron for prevention of nausea and vomiting caused by interleukin-2- (IL2) based biochemotherapy

Patients who were treatment naïve were randomized to one of two dosing schedules for 0.25 mg IV palonosetron for prophylaxis of chemotherapy-induced nausea and vomiting (CINV). Schedule one was on days 1 and 4, and schedule two was on days 1, 3, and 5. All patients received the same chemotherapy/biotherapy regimen, which consisted of dacarbazine on day 1; cisplatin, vinblastine, and IL-2 on days 1-4; and interferon (IFN) alpha 2b on days 1–5 as part of a 21-day cycle. Patients also received 0.5–1 mg IV lorazepam every 8 hours. Rescue medications were 50 mg IV metoclopramide with 25 mg IV diphenhydramine every 4 hours, 10 mg IV prochlorperazine every 4 hours, or a combination of lorazepam, diphenhydramine, and haloperidol compounded in hospital pharmacy. An episode of nausea or vomiting was defined as nausea or vomiting of any severity reported by the patient or documented by the nursing staff at any time during the 21-day treatment cycle as well as the need for rescue medication during the first 7 days. Patient diaries were used to document episodes of nausea and vomiting and the antiemetic used to control them. Function Living Index-Emesis (FLIE) was used to assess the patient’s quality of life daily for days 1–7.

• The study reported on 30 patients with a median age of 53.
• The sample was 60% male and 40% female.
• Patients had been diagnosed with stage III–IV metastatic melanoma and had European Cooperative Oncology Group (ECOG) performance statuses of 0–1 and expected survival greater than eight weeks.

This was a single site, inpatient study conducted at the M.D. Anderson Cancer Center in Houston, TX.

Patients were undergoing the active treatment phase of care.

This was a randomized, two-group, comparison study.

• Patients used the FLIE to evaluate quality of life.
• Patient diaries were used to document episodes of nausea and vomiting and use of antiemetics.

Each group (schedule 1 and schedule 2) had 15 patients. For the first 7 days of treatment, more episodes of nausea were reported for schedule 1 than schedule 2, but the difference was not statistically significant (p = 0.16). A similar trend was observed when comparing the number of episodes of emesis during the first 7 days (p = 0.20), the number of antiemetic rescue doses required (p = 0.30), and number of episodes of nausea and emesis during the first 21 days. Evaluation of the FLIE revealed similar proportion of patients on schedule 1 and 2 experiencing interference with appetite, sleep, physical activity, social life, and enjoyment of life (p = 0.071).

Because of the small sample size, differences in dosing schedule efficacy cannot be determined with confidence. However, a trend toward better control of CINV was noted with more frequent palonosetron dosing.

• The sample size was small, with fewer than 100 patients.
• The study was not powered or designed to show statistical differences. The patients in the schedule 1 group had higher prevalence of liver metastasis; while not statistically significant, sample size may not be large enough to determine if this was significant.  

Corticosteroids for the prevention of biochemotherapy-induced nausea and vomiting are contraindicated because they cause lysis of lymphokine-activated killer (LAK) cells produced in response to IL-2, which makes control of CINV challenging. This study does not provide evidence to support use of antiemetic schedule 1 versus schedule 2. More research is needed.

To investigate the influence of parecoxib on morphine analgesia after gynecological tumor surgery

The test group (group P) was given 40 mg IV parecoxib prior to induction of anesthesia and 40 mg IV q 12 hours for 48 hours after the operation. The control group (group C) was given 2 ml saline at the same time intervals. Both groups were introduced to a patient-controlled analgesia (PCA) device and documentation of postoperative pain or adverse effects on Visual Analog Scale (VAS).

• N = 79  
• AGE RANGE = 18–60 years
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Gynecological tumor
• OTHER KEY SAMPLE CHARACTERISTICS: American Society of Anesthesiologists (ASA) physical status I-II

• SITE: Single-site    
• SETTING TYPE: Inpatient    
• LOCATION: Guangzhou, China

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

Placebo-controlled, randomized, controlled trial

• Visual Analog Scale (VAS)
• Morphine requirement
• Satisfaction score and side effects
• Sedation scale

There was a reduction of about 9% in the total morphine requirement used within the first 48 hours after gynecological tumor surgery, and overall satisfaction scores were 8.6 versus 6.8 (groups P and C, respectively). Pain scores at rest and with movement were significantly lower in the parecoxib group at all postoperative time points (p < .001).

The use of parecoxib with patient-controlled analgesic morphine in postoperative analgesia resulted in enhanced analgesic efficacy, reducing the opioid requirement, increasing patient satisfaction, and reducing pain severity after gynecological tumor surgery.

• Small sample (< 100)
• Other limitations/explanation: With regard to reporting and assessing side effects, specifically nausea, vomiting, urinary retention, and sedation, the authors reported the differences were clinically insignificant. However, the control group had twice as many reports of nausea, vomiting, and urinary retention in the 48 hours postoperatively compared to the test group (P) as well as a 7% increase in reports of sedation. The study limited itself to the use of PCA morphine only. Additional studies would be of benefit to determine the influence of parecoxib on morphine use (small study size).

This study has positive implications for nursing and healthcare professionals as it did show a 9% decrease in morphine PCA use in the first 48 hours postoperatively with fewer reported side effects. This study should be replicated with a larger sample size to validate its findings.

To evaluate the effects of irsogladine maleate (IM) on fluorouracil-induced oral mucositis

Patients were randomly assigned to irsogladin maleate (IM) or placebo or normal saline. Treatment was administered orally twice a day, 4 mg/day beginning on the first day of chemotherapy and continued for 14 days. Oral rinse with sodium gualenate hydrate, standard care was also used 4 times daily. Other oral treatments were not allowed. Patients were assessed on days 1, 3, 5, 8, 10, 12, 14, 21, and at the end of the chemotherapy cycle.

The sample was comprised of 66 patients. Age in the IM arm: 35-79, in the placebo arm 30-79 .

MALES (%) IM arm n = 20 and placebo arm n = 21; FEMALES (%) IM arm n = 13 and placebo n = 12.

KEY DISEASE CHARACTERISTICS: 83% of all patients had tumors in the head and neck or esophagus.

OTHER KEY SAMPLE CHARACTERISTICS: Most patients had stage III-IV tumors. Chemotherapy included 5FU and cisplatin or nedaplatin.

SITE: Single site

SETTING TYPE: Inpatient

LOCATION: Kansai Medical University, Hirakata, Japan

PHASE OF CARE: Active antitumor treatment

APPLICATIONS: Elder care

Double blind randomized placebo controlled

WHO grading of oral mucositis
NCI – CTCAE

Incidence of oral mucositis was 27.3% in the IM group and 72.7% in the placebo group (hazard ratio 0.14, 95% CI 0.05-0.42, p < 0.001). Changes in oral mucositis showed that severity scores were significantly lower in the IM group on multiple study days (p < 0.05). No adverse events related to IM were found.

This study adds to the evidence suggesting that IM is useful in the prevention of oral mucositis.

Small sample (<100)

Key sample group differences that could influence results

Other limitations/*explanation: There is no information regarding patient adherence to the protocol for frequency of medication use.

This study showed that irsogladine maleate use was associated with reduced incidence and severity of oral mucositis in these patients receiving chemotherapy associated with development of mucositis. There are few treatments that have been shown to be effective for mucositis prophylaxis. Given the promising results in this relatively small study, further research is warranted.

To clarify the efficacy of Goshajinkigan (GJG) for peripheral neuropathy associated with oxaliplatin

Intervention Studies: From January 2007 through December 2009, 45 patients with advanced or recurrent colorectal cancer who were being treated with 5-fluorouracil, oxaliplatin, and leucovorin (FOLFOX) every two weeks participated in the study. Patients were randomized to receive either oral GJG (7.5 g/daily) or no drug. The median number of cycles was 13 for the patients in the GJG group and 12 for the control group. Neuropathy was evaluated during every course according to the Neurotoxicity Criteria of Debiopharm. Other neuromodulatory agents such as calcium and magnesium infusions were not allowed during the study. Oxaliplatin dose was reduced in the event of grade 3 neuropathy.

• N = 21      
• MEDIAN AGE = 67 years
• MALES = 51%,  FEMALES = 49%
• KEY DISEASE CHARACTERISTICS: The GJG group included 15 patients with colon cancer and 7 patients with rectal cancer. The control group included 16 patients with colon cancer and 7 patients with rectal cancer.
• OTHER KEY SAMPLE CHARACTERISTICS: 82% had received no previous treatment. The median cumulative dose of oxaliplatin was 1112.5 mg/m², with a range of 340–2720.

• SITE: Single site
• SETTING TYPE: Outpatient
• LOCATION: Tokushima University Hospital in Tokushima, Japan

• PHASE OF CARE: Active treatment
• APPLICATIONS: Late effects and survivorship

Prospective, randomized, controlled trial

Patients were evaluated at baseline and during their every-two-weeks treatment course according to the Neurotoxicity Criteria of Debiopharm.

The incidence of grade 3 peripheral neuropathy in the GJG group was significantly lower than in the control group (p < 0.01, log-rank test). The incidence of grade 3 peripheral neuropathy after 10 courses was 0% in the GJG group and 12% in the control group. After 20 courses, it was 33% in the GJG group and 75% in the control group. The only differences in adverse effects between the two groups were peripheral neuropathy and influence on tumor response.

A randomized, double-blind, placebo-controlled trial would be needed to determine efficacy of this oriental herbal medication. No trials with GJG have been conducted in the United States, so no history exists of it being used as an intervention for chemotherapy-induced peripheral neuropathy. These preliminary findings suggest that further research in use of GJG may be warranted.

• Small sample < 30
• Not placebo-controlled
• Not double-blind
• The Neurotoxicity Criteria of Debiopharm was not described. Several other neurotoxicity scales, even a specific oxaliplatin scale, exist. No explanation was provided for why this scale was chosen.
• Sample characteristics of those randomized are provided; however, characteristics of only those who actually completed the study are not described.
• GJG is an oriental herb and would need further testing to be used in the United States in a clinical trial.

Although it has shown some positive results in reducing neuropathy in a clinical trial in Japan, GJG can not be recommended for treating chemotherapy-induced peripheral neuropathy in the United States until further testing occurs in a large, randomized, double-blind study.

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.