PURPOSE: Review the benefit of polyvinylpyrrolidone-sodium hyaluronate gel (Gelclair) for oral mucositis

RESOURCE TYPE: Expert opinion

PHASE OF CARE: Active treatment

Various uses and mechanism of action of hyaluronic gel (Gelclair) are discussed. Six studies/articles are summarized. Only one article provided any significant findings. One other article related to oral mucositis was a case study. The author suggests that Gelclair may be a useful additional therapy to help with pain caused by oral lesions. It may contribute to improved drinking, eating, and swallowing, and may improve nutritional status and quality of life.

May be effective for pain related to mucositis

A large control trial is needed to increase the strength of recommending Gelclair. Evidence provided here is weak and very limited regarding examination of Gelclair for oral mucositis in patients with cancer.

To compare the effects of resistance versus aerobic exercise on lymphedema and fitness in women with breast cancer

Women were randomly assigned to exercise mode. Resistance exercise included a full-body strength training program with a gradual introduction of additional exercises for a total of 12 exercises by week 7. The aerobic group was involved in a range of exercises depending upon preference, such as walking, jogging, cycling, or swimming. Both groups were assigned to 150 minutes of supervised and unsupervised exercise each week at a metabolic equivalent of task (MET) level of 5 in weeks 7–12. Supervised one-on-one exercise sessions were held at the patients’ homes or other selected locations. Assessments were conducted at 12 and 24 weeks.

• N = 41   
• MEAN AGE = 56 years
• KEY DISEASE CHARACTERISTICS: Patients with breast cancer with a history of stable arm lymphedema, with an average of 56 months since initial diagnosis. All had stage I or II lymphedema.
• OTHER KEY SAMPLE CHARACTERISTICS: Women who reported usual exercise levels exceeding 75 minutes per week were excluded.

• SITE: Single site   
• SETTING TYPE: Multiple settings    
• LOCATION: Australia

PHASE OF CARE: Late effects and survivorship

Randomized, two-group trial stratified by lymphedema stage

• Bioimpedance spectroscopy
• Circumference measurement 
• Norman lymphedema survey
• Numerous body strength and endurance measurements
• Functional Assessment of Cancer Therapy-Breast (FACT-B), version 4
• Exercise logs

Ninety-two percent completed at least 75% of exercise sessions. No differences existed between groups or over time in lymphedema or associated symptoms. The aerobic group showed a decline in the number of symptoms at 12 weeks (–1.5 change in score, p = 0.05). Both groups improved upper body strength, and improvements were greater in the resistance exercise group (p < 0.01). Both groups had improved lower body strength and FACT-B measures.

Neither resistance nor aerobic exercise significantly improved objective measures of lymphedema. Both exercise modes were associated with improvement in fitness, strength, and quality of life.

• Small sample (< 100)
• Risk of bias (no blinding)
• Frequency of supervised exercise sessions is unclear.

Results from this study did not show that either resistance or aerobic exercise resulted in volume reduction of lymphedema. Both forms of exercise were associated with improved fitness, strength, endurance, and aspects of quality of life. Exercise has been shown not to increase lymphedema in several studies, and although it may not reduce lymphedema volume, it can be beneficial in other aspects. Nurses can educate patients to engage in physical activity and exercise.

Adult patients with cancer whose chemotherapy-induced neutropenia (absolute neutrophil count [ANC] greater than 1,000) was expected to occur for more than seven days were treated with oral levofloxacin 500 mg or placebo from the start of chemotherapy until the resolution of neutropenia.

Primary endpoint:

• Incidence of fever

Secondary endpoints:

• Type and number of microbiologically-documented infections
• Use of parenteral antimicrobials
• Compliance
• Tolerability
• Survival 
   

• 760 hospitalized adult patients with cancer who were expected to develop chemotherapy-induced neutropenia lasting longer than seven days.
• The sample included patients with the following types of cancer: leukemia, 49%; non-Hodgkin lymphoma or Hodgkin disease, 31%; other hematologic cancers,13%; and solid tumors, 7%.

• Inpatient
• 35 medical centers in Italy

the study was a prospective, multicenter, randomized, double-blind, placebo-controlled trial,

• Patients were examined daily for signs of infection.
• In the event of fever or suspected infection, microbiologic cultures were obtained, including at least two separate blood cultures.
• Infections were classified according to definitions of the European Organisation for Research and Treatment of Cancer ( EORTC).
• Compliance was determined by counting pills.

The incidence of fever (axillary temperature 38.5°C or higher, or 38°C at least twice during a 12-hour period) was 65% in the levofloxacin prophylaxis group versus 85% in the placebo group (p = 0.001). Microbiologically documented infection occurred in 22% of patients in the levofloxacin group and 39% of patients in the control group (absolute risk reduction 17%, 95% confidence interval [CI] [24, 10], p < 0.001).

In the levofloxacin group, the incidence of bacteremias (risk reduction 16%, 95% CI [22, 9], p < 0.001) and single-agent gram-negative bacteremias (risk reduction of 7%, 95% CI [10, 2], p < 0.01) was lower.

Death from infection occurred in 2.4% of patients in the levofloxacin group and 3.8% of patients in control group (p = 0.36).

The median duration of prophylaxis was 14 days for patients with solid tumors or lymphoma and 25 days for patients with leukemia.

Overall mortality was 3% in the levofloxacin group and 5% in the placebo group (p = 0.15). Infection-related mortality was 2% in the levofloxacin group and 4% in the placebo group (p = 0.36).

Compliance and reported adverse events were similar in both groups.

The prevalence of fluoroquinolone-resistant bacteremias was 41 of 339 (12%) in the levofloxacin group and 32 of 336 (9.5%) in the control group, but this result was not statistically significant.

The total cost of antibiotics per patient was less in the levofloxacin-treated group. The mean cost of antibiotics was €1,953 in the levofloxacin group and €2,841 in the control group.
 

Most of the patients had hematologic malignancies, so the study supports the use of antibacterial prophylaxis in this population. However, survival advantage with antibiotic prophylaxis was not demonstrated in the study.

There is concern that routine use of antibiotics is associated with an increase in resistant organisms.

The discussion section states that the study provides evidence that prophylaxis is economical because risk of fever is reduced.

To evaluate the efficacy and safety of palonosetron followed by dexamethasone administered as a single dose for the prevention of vomiting and nausea in patients receiving moderately emetogenic chemotherapy for breast and colorectal cancer

A bolus dose of 0.25 mg IV palonosetron was given over 30 seconds beginning 30 minutes before chemotherapy, followed by 8 mg IV dexamethasone. Patients were asked to complete diaries to assess antiemetic response during the acute, delayed, and overall phases (days 1–5).

• The study consisted of 68 patients, 40 with breast cancer and 28 with colorectal cancer.
• Mean age was 61 years.
• The sample was 21% male and 79% female.
• Patients had been diagnosed with colorectal or breast cancer and were chemotherapy-naïve.
• Race/ethnicity was not specified.
• To be included, patients had to be over age 18, have a European Cooperative Oncology Group (ECOG) performance status of 0–1, and have acceptable liver and kidney function.
• Patients were exclused if they had received radiation within 30 days of initiation of chemotherapy; had previous history of vomiting episodes, including morning sickness or motion sickness; and had any concomitant severe disease.

This study was conducted at a single outpatient site in Cinisello Balsamo, Italy.

• All patients were in active treatment.
• This study has application for late effects and survivorship.

This was a phase II, open label, nonrandomized prospective study.

• The primary endpoint was the overall complete response (no nausea or vomiting), defined as the percentage of patients with no use of rescue antiemetic.     
• Secondary endpoints were evaluated at three different stages of treatment: Acute, delayed and overall percentage of complete response.
• Self report diaries of all activities from day 1 to day 5 included the onset of emesis, nausea (measured using a Likert-type scale) and its severity, and the use of rescue medications.
• Overall satisfaction with antiemetic therapy was measured using a visual analog scale (VAS).

• Complete response was observed in 67.6% of patients. Complete response during the acute and delayed phases was 75% for both cancer groups.
• Complete control was 67% overall.  A statistically significant effect of palonosetron was observed for control of emesis and nausea.
• The percentage of patients experiencing adverse events was 36.7%.

Palonosetron followed by dexamethasone in a single administration before chemotherapy to patients with breast or colorectal cancer provides significant protection during the overall phases of chemotherapy. Patients reported high satisfaction with this regimen.

• The sample size was small with fewer than 100 patients.
• The authors stated that 20 (50%) of the women with breast cancer had radical surgery prior to initiation of chemotherapy. They do not include postoperative nausea and vomiting (PONV) specifically as exclusion criteria, but it would be interesting to know if this might influence the results because motion sickness and morning sickness were exclusion criteria.

Palonosetron followed by dexamethasone should be considered as premedication on day 1 in moderately emetogenic chemotherapy regimens in patients with breast or colorectal cancer.

Although a complete response was observed in 67% of patients, 33% did not experience complete response. Despite this, the authors stated that this medication regimen adequately controlled CINV during the entire period of emetic risk. Additionally, the 33% of nonresponders does not include high-risk patients who were excluded from this study because of a history of previous nausea and vomiting.

The key takeaway for nurses is that a significant number of patients may require both pharmacologic and nonpharmacologic strategies  to help them through this time.

The study involved patient-controlled administration of immediate-release methylphenidate 5 to 20 mg per day, taken as often as every two hours based on the hypothesis that treatment with a psychostimulant (methylphenidate) would reduce perceived fatigue.

• In total, 30 patients with a median age of 51 years (range 24–79) were included. 
• Most patients were women. 
• The sample included a mix of primary cancer diagnoses, including head and neck, gynecologic, and hematologic cancers.
• All patients had normal thyroid function and a hemoglobin level of 10 mg/dL or greater at study inception.
• Patients with central nervous system disease, a history of seizures, or significant hepatic, renal, or cardiac dysfunction were excluded.

Patients were recruited from a palliative care outpatient clinic or a pain clinic of a large university cancer center.

Unspecified

The study used a single-center pilot study prospective, open-label design; no comparison group was included.

• Functional Assessment for Chronic Illness Therapy–Fatigue (FACIT-F)
• Edmonton Symptom Assessment Score (ESAS)
• Patients rated their drowsiness, ability to sleep at night, pain, depression, and nervousness using a numeric scale from 0 to 10.

Of the patients, 93% (n = 28) reported improvements in fatigue from baseline to day 7 of study participation (as measured by the fatigue item on the ESAS and FACIT-F). Of the patients, 93% took three or more methylphenidate tablets daily. All patients chose to continue methylphenidate for at least four weeks beyond the initial study period of seven days. The following side effects were reported by two or less participants:  restlessness, dizziness, anorexia, skin rash, and self-limited vertigo and tachycardia.

• This was an open-label study, with no randomization, control, or comparison group.
• A small convenience sample was used.
• No stratification existed for the presence or absence of depression.
• Safety was not evaluated in patients with central nervous system disease, a history of seizures, or significant hepatic, renal, or cardiac dysfunction.

No special training is required to deliver the intervention; the costs are related to drug acquisition.

Patients were given a daily dose of up to 18 gel capsules, including

• 1,000 mg of fish oil, 1,800 mg of eicosapentaenoic acid (EPA), 120 mg of docosahexaenoic acid (DHA), and 1 mg of Vitamin E.
• Placebo was 1,000 mg of olive oil.

• The sample was comprised of 91 adult patients with locally recurrent or metastatic cancer. Each arm had 30 patients.
• Of the patients, 31% dropped out.
• Patients were included if they had anorexia, weight loss more than 5% of their preillness weight, were able to intake orally, and had normal cognition.

The study was conducted at a Canadian acute palliative care unit and the inpatient and outpatient units of a cancer center.

The study was a double-blind, placebo-controlled trial.

• Tiredness visual analog scale (VAS), ranging from 1 to 10
• Karnofsky Performance Status (KPS)

Patients could not take 18 large capsules every day; the mean was 12 per day, with five patients in each group dropping out.

A strong trend was observed toward improved appetite in both groups. With the fish oil group, a trend existed toward less tiredness, but no significant change existed with appetite, weight loss, or calories.

Side effects of fish oil capsules included belching and fish oil taste.

• The study was of short duration.
• A lack of symptom improvement was observed.
• Capsules were not well tolerated.
• Long-term compliance was doubtful.
• Gastrointestinal symptoms occurred with fish oil and placebo, causing oily diarrhea and an inability to tolerate them in the esophagus or stomach.

Patients received either donepezil or placebo (5 mg) orally every morning for seven days. A research nurse contacted patients by daily telephone calls to assess symptoms and treatment toxicity. Patients were evaluated at the clinic on day 8. Patients returned for a final assessment on day 15, and those who chose to continue taking donepezil were provided with a two-week supply of the drug. Fatigue outcomes were assessed at baseline, day 8, and day 15.

• N = 142; 103 patients were assessable for the final analysis
• MEAN AGE = 56 years
• FEMALES: 65%
• KEY DISEASE CHARACTERISTICS: Patients with advanced cancer, defined as locally recurrent or metastatic; the primary cancer site was most often breast.
• EXCLUSION CRITERIA: Women who were pregnant or lactating, use of tube feeding, cardiac complications, urinary incontinence, presence of concurrent nausea, vomiting, diarrhea, major contraindication to donepezil, major changes expected in the next seven days, administration of anticholinergic agents, hemoglobin less than 1 g/dL within four weeks before enrollment

• Patients were recruited from palliative care or pain clinics at the MD Anderson Cancer Center and the Lyndon B. Johnson General Hospital.

• Active treatment

• Prospective, open-label, pilot, double-blind, randomized, placebo-controlled trial
  • Donepezil intervention (N = 47)
  • Placebo (N = 56)

• Functional Assessment for Chronic Illness Therapy-Fatigue (FACIT-F)

The donepezil intervention did not show any improvement in fatigue in comparison to the placebo, as no significant difference was seen between groups at baseline and on day 8 for FACIT-F fatigue intensity scores.

• Small sample size
• Intervention only lasted a week, so long-term effects of donepezil remain unknown.

Donepezil 5 mg every morning for seven days

• N = 27
• MEDIAN AGE = 52 years (range: 24–75 years)
• FEMALES: 67%
• KEY DISEASE CHARACTERISTICS: Mixed cancer diagnoses, including hematologic, gastrointestinal, lung, head and neck, and breast
• OTHER KEY SAMPLE CHARACTERISTICS: Median oral morphine-equivalent daily dose was 180 mg per day (range: 30–600)

• SETTING TYPE: Mixed inpatient and outpatient
• LOCATION: Academic cancer center

• PHASE OF CARE: Unclear

• Open label, prospective, non-randomized pilot study 
• No comparison/control group

• Edmonton Symptom Assessment Scale (ESAS)
• Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue)

Fatigue significantly was improved following a seven-day course of treatment with donepezil. Significant improvement was noted in anxiety, well-being, sleep problems, depression, and anorexia. Pain level was unchanged. Of the initial 27 patients enrolled in the study, 7 patients were discontinued from the study due to cellulitis (1 patient), concern about a possible drug-drug interaction (1 patient), transient arterial hypertension (1 patient), increasing muscle cramps (1 patient), and mild to moderate nausea (3 patients).

• Open-label trial without a comparison group
• Small sample size
• Short length of treatment and minimal follow-up to examine longer-term side effect profile

Compare the effects of methylphenidate (MP) (psychostimulant) with those of a placebo (PL) on cancer-related fatigue. The effect of a combined intervention including MP plus a nursing telephone intervention (NTI) also was assessed.

Patients with a fatigue score of greater than or equal to 4 out of 10 on the Edmonton Symptom Assessment Scale (ESAS) randomly were assigned to one of the following four groups: MP plus NTI, PL plus NTI, MP plus control telephone intervention (CTI), and PL plus CTI.

• N = 141
• MEDIAN AGE = 58 years
• MALES: 33%, FEMALES: 67%
• KEY DISEASE CHARACTERISTICS: Diagnosis of advanced cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Four or above on the ESAS, normal score on the Mini Mental State Examination (MMSE), no severe comorbid conditions including severe anxiety, major depression, substance abuse, or erythropoietin use

• SITE: Multi-site  
• SETTING TYPE: Outpatient  
• LOCATION: Outpatient palliative care and oncology clinics at MD Anderson Cancer Center and at Lyndon B. Johnson General Hospital, both in Houston, TX

• PHASE OF CARE: Mutliple phases of care
• APPLICATIONS: Pediatrics, elder care, palliative care

Randomized, controlled trial; placebo controlled

• Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F)
• ESAS
• MMSE
• Hospital Anxiety and Depression Scale (HADS)
• Pittsburgh Sleep Quality Index (PSQI)

The groups MP alone, NTI alone, or MP plus NTI proved not significantly better than PL for cancer-related fatigue. Anxiety improved with the telephone intervention (p = .01), as did sleep (p < .001).

MP, used alone or in combination with NTI, was not superior to the control group or the PL for fatigue or depression. NTI was associated with improvement in anxiety and sleep.

• Risk of bias (no blinding)
• No statistical control for multiple comparisons, which could lead to a type one error
• Limited duration of two weeks  
• Content of CTI not described

Although the use of MP did not prove to be effective for cancer-related fatigue, several cancer-related symptoms significantly were improved with NTI. Further research in this area would be ideal, but NTIs remain potentially effective for patient support and education and can have a positive effect on patient experience.

The objective of the study is to determine the effectiveness of oxygen versus air to decrease dyspnea and fatigue and to increase distance walked during a six-minute walk test.

Oxygen or air was delivered via nasal cannula during a six-minute walk test.

The study reported on a sample of 33 patients.

The study had the following inclusion criteria.

• Ambulatory patients with normal cognitive status
• Hemoglobin greater than 10
• No evidence of acute respiratory distress
• Resting pulse oxygenation percent greater than 90%

Patients were excluded if they were on oxygen therapy.

Double-blind, randomized, controlled crossover study

Fatigue and dyspnea were evaluated by a visual analog scale (0 = absence of symptoms and 10 = worst possible symptoms). Respiratory rate and heart rate were monitored. The outcomes measured were dyspnea at three and six minutes, fatigue at six minutes, and distance walked. This was repeated when patients received the crossover treatment. Patients and researchers both rated dyspnea. Oxygen saturation was measured at baseline before the crossover and at completion of the study.

No significant differences were noted between the two groups observed. Dyspnea score at three minutes, dyspnea score at six minutes, fatigue score at six minutes, and distance in feet walked at six minutes were not statically significant (p > 0.52). The authors concluded that the routine use of supplemental oxygen for dyspnea during exercise in this patient population cannot be recommended.

• The study had a small sample size of 33.
• It was a small single-site study.
• No pulse oximetry measurements were taken at the beginning or end of the six-minute exercise.