To determine the effectiveness of date palm pollen (DPP) in the prevention and treatment of oral mucositis in patients undergoing radiation and chemotherapy for head and neck cancer

Two grams of DPP in powder form were mixed in 125 mL of water by the subjects. Patients were instructed to swish and swallow nightly for 42 days starting the day before treatment. The Oral Mucositis Assessment Scale (OMAS) was completed at days 0, 15, and 29. The first 10 subjects were enrolled in the treatment arm and the next10 subjects were in the control arm.

• N = 20  
• MEDIAN AGE = 43.5 years (treatment), 47.5 years (control)
• MALES: 55%, FEMALES: 45%
• KEY DISEASE CHARACTERISTICS: The treatment group included squamous cell carcinoma, adenocarcinoma, and Hodgkin’s lymphoma. The control group included squamous cell carcinoma only.
• OTHER KEY SAMPLE CHARACTERISTICS: Chemotherapy consisted of cisplatin 100 mg/m² every three weeks for three cycles; radiation therapy consisted of 50–72 Gy in 200 cGY conventional fractionation. The treatment group included two patients who received radiation therapy only.

• SITE: Single-site
• SETTING TYPE: Outpatient
• LOCATION: Not indicated

• PHASE OF CARE: Active antitumor treatment

Controlled trial; control group received facility standard of care

• Oral Mucositis Assessment Scale (OMAS) 
• Visual Analog Scale (VAS)

The mean OMAS score was lower in the DPP-treated group with statistically significant differences on day 15 (p < .05) and day 21 (p < .05). The mean oral pain intensity level was lower in the DPP group on day 15 (p < .05) and day 21 (p < .05). Only one patient in the DPP group required soft food compared to 80% in the control group. There was a significant difference in the mean impact on swallowing on day 15 (p < .05) and day 21 (p < .05).

There was a significant reduction in the severity and incidence of mucositis as indicated by the OMAS and the VAS pain scales.

• Small sample (< 30)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Other limitations/explanation: Assessments were completed on days 0, 15, and 29, and the patients were told to self-administer the treatment for 42 days. Patients in the control group received 20 mg/g miconazole, rebamipide, and oral analgesics as needed. The authors reported no treatment compliance issues.

Although the mechanism of DPP is not totally clear, nurses should recognize that there are many plant derivatives that may have positive effects on oral mucositis. Larger, randomized trials of these agents are needed.

To evaluate the use of oral transmucosal fentanyl citrate (OTFC) as a rescue or breakthrough medication to relieve dyspnea

This study described four individual case reports. In case 1, the patient received 1,200 mcg of OTFC as breakthrough dose (BT) for dyspnea while on 400 mg/d IV morphine. In case 2, the patient received 800 mcg of OTFC as BT for dyspnea while on 90 mg of oral morphine every 24 hours. In case 3, 600 mcg of OTFC originally was prescribed for pain was reported to relieve dyspnea. In case 4, the patient was given 400 mcg OTFC while on 15 mg/d IV morphine.

The case reports were of four patients who were terminally ill with cancer (two women and two men). Three patients had lung cancer, and one had colon cancer. OTFC was chosen for its rapid effect and ease of administration.

Cases 1, 2, and 4 were conducted at an inpatient hospice unit, and case 3 was conducted at home.

Cases 1 , 2, and 4 used numeric rating scales (NRSs), and case 3 used percent improvement.

• The patient in case 1 experienced a decrease in dyspnea at rest from 7/10 to 2/10 at 22 minutes following OTFC 1,200 mcg with no alteration in oxygen saturation percentage.
• In case 2, the patient experienced a 100% decrease in dyspnea from 5/10 at 15 minutes after second dose of 400 mcg of OTFC (total = 800 mcg) with a decrease in respiratory rate to 18 and no change in oxygen saturation percentage.
• In case 3, the patient experienced 100% relief of dyspnea at 20-30 minutes after use.
• The patient in case 4 showed a 40% improvement from 7/10 rating at 15 minutes, 75% at 30 minutes, and 90% at 45 minutes with 100% at 60 minutes.

These reports showed that OTFC improved dyspnea in individual cases, was easy to administer, and provided rapid onset of relief and minor adverse effects. The specific doses were variable and chosen according to patients’ baseline opioid use.

• Case reports only give anecdotal findings and provide lower levels of evidence.
• Two patients reported moderate somnolence and dizziness side effects after OTFC.

To demonstrate the use of prophylactic antibiotics to prevent fever in autologous stem cell transplantation recipients.

Researchers used antibiotics prophylactically (ciprofloxacin and vancomycin) to prevent ElE infections during the neutropenic stage of transplantation.  Patients were randomly assigned to receive 500 mg of ciprofloxacin orally twice a day and 1000 mg of vancomycin intravenously (IV) daily or no prophylactic antibiotic use.  Antibiotics were given on day 0 and continued until neutropenia resolution or the occurrence of a febrile event.  Antibiotics were given to any patient who experienced a febrile event.  All patients received lenogastrim three days after cyclophosphamide and until harvesting and also from posttransplant day 1 until the white blood cell (WBC) count was >10x10³ µg/dL.

• One hundred fifty-seven patients were included.
• Patients were older than 18 years.
• The numbers and percentages of males and females were not specified.
• Key disease characteristics were multiple myeloma, hematological malignancies, and solid tumors.
• Most patients received high-dose mephalan.
   

• Single site  
• Inpatient  
• Greece
   

• Patients were undergoing the active treatment phase of care.
• The study has clinical applicability for late effects and survivorship. 
   

This was a randomized, controlled study.

• Incidence of febrile episodes with an axillary temperature of 38ºC over 12 hours on two or more occasions or a temperature of 38.5°C with neutropenia
• European Organization for Research and Treatment of Cancer(EORTC)/Invasive Fungal Infections Cooperative Group definitions

Between cell reinfusion and bone marrow reconstitution, 71.3% of patients receiving prophylactic antibiotics developed neutropenic fever, compared with 91.2% of those receiving only supportive care (p < 0.001). Patients receiving the combination of ciprofloxacin and IV vancomycin had a significantly lower rate of bacteremias (5.6%) than those with no prophylaxis (35%) (p = 0.005).  The cumulative hazard ratio (HR) of fever for randomized patients demonstrated a statistical benefit in favor of prophylactic antibiotics (HR = 2.43; 95% confidence interval [1.60, 3.49]; p < 0.001). There were no infection-related deaths in the sample.  There were no differences between groups in duration of hospitalization. Median duration of treatment was six days.  Patients were followed for one month in the study.  Five patients developed severe skin rash attributed to antibiotics and discontinued treatment.  There were no clear differences between groups in adverse effects, and no other effects were severe enough to warrant discontinuation of antibiotics.

This article showed that the prophylactic antibiotics oral ciprofloxacin and IV vancomycin help to prevent neutropenic fever after transplant but that their usage is not helpful in either decreasing the overall length of stay in the hospital or decreasing the risk of complication-related deaths.

• No blinding was performed, which had a related risk of bias.
• Limited sample demographic and disease-related information was provided, so it is unclear how much the findings can be generalized. 
• Cost-effectiveness of antibiotic prophylaxis was unclear.

Findings support the use of prophylactic antibiotic therapy for reducing the prevalence of febrile neutropenia in this group of patients.

To assess the efficacy of a visible-light therapy device for the prevention of OM in HSCT patients.

All patients received preventive protocols that included prophylactic antivirals for those at risk for infection, cyclosporine as GVHD prophylaxis in allogeneic transplant patients, and standard topical antibacterial and antifungal prophylaxis with chlorhexidine, Nystatin, and saline rinses. Subjects were randomized to the study group (N = 10) who received broad band visible light (BBVLT) therapy starting on the first day of conditioning 5 times per week, continuing until at least day 21 if score was 0 on OMAS and WHO Scales. Subjects assigned to the placebo group received sham therapy using a similar device. Otherwise treatment was continued until day 28. Patients were evaluated daily, and oral mucosa was evaluated weekly by the research team.

The study was comprised of 19 patients, age 24.5 - 66 years.

Males (%): 53, Females (%): 47

Key Disease Characteristics: Leukemia, lymphoma, five patients listed as other (2 active Rx, 3 Placebo).

Other Key Sample Characteristics: Adult patients receiving myeloablative and non-myeloablative conditioning regimens with chemo + or - TBI and prophylaxis. Examined prior to treatment to confirm intact mucosal lining. Karnofsky score greater than 60.

Site: Single site

Setting Type: Not specified

Location: Hadassah University Medical Center - Department of Bone Marrow Transplantation

Phase of Care: Active treatment

Randomized, placebo controlled and double blinded

• WHO Mucositis Scale    
• Oral Mucositis Assessment Scale
• BB-VLT device
• Clinical exam daily by the attending physician. Weekly oral mucosa monitoring by the research team.
• Pain was scaled weekly using a VAS 0 - 10 analog scale.
• Satisfaction with treatment modality were evaluated on 0-10 scale.
   

There was a statistically significant difference in both the frequency of patients with no mucositis and the severity of the mucositis based on the WHO and OMAS scales at visit three only (p = 0.02) . Other than that, there were no statistically significant differences in frequency or severity of mucositis between the two groups.  There was no significant difference in narcotic consumption between the two groups. Satisfaction was highly rated in both groups.

There were significantly better mucositis scores and lower pain levels in the treatment group at one week post-HSCT. Treatment was well tolerated with no adverse events related to the study device. The conclusion is that the BB-VLT device is safe and effective in the prevention of oral mucositis in HCST patients.

Small sample <30

Costly treatment, though less so than lasers. Significant differences were seen at only one time point.

Needs further study, though device appears easy to use and safe. BBVLT therapy may be a less costly alternative to laser treatments, and the device used could be operated by patients themselves for self care. Larger studies in this area are warranted.

RESOURCE TYPE: Consensus-based guideline

PROCESS OF DEVELOPMENT: A literature search for papers published between January 1, 2009, and January 6, 2015, related to high-dose chemotherapy, multiple-day chemotherapy regimens, and breakthrough nausea and vomiting

DATABASES USED: PubMed

INCLUSION CRITERIA: Clinical trials, systematic reviews, stem cell transplantations (SCTs), patients with germ cell tumors

EXCLUSION CRITERIA: Other studies

PHASE OF CARE: Active antitumor treatment

Few studies related to the prevention of acute and delayed CINV in patients receiving high-dose and multiple-day chemotherapy regimens and for breakthrough nausea and vomiting. Little evidence related to the control of nausea exists.

Aprepitant should be added to two-drug antiemetic regimens in patients receiving high-dose and multiple-day cisplatin regimens to prevent acute and delayed CINV. Olanzapine is recommended for breakthrough CINV.

To evaluate topics related to nausea and vomiting, specifically antiemetic therapy in high-dose chemotherapy with stem cell transplant and the use of rescue antiemetic for refractory emesis, with the intention of developing a consensus statement

Recommendations were rated using the Multinational Association of Supportive Care in Cancer (MASCC) and European Society for Medical Oncology (ESMO) levels of confidence for evidence strength rating.

Patients were in active treatment.

Patients receiving multiple-day cisplatin should receive a 5-HT₃ receptor antagonist plus dexamethasone for acute nausea and vomiting and dexamethasone for delayed nausea and vomiting. Because emesis in progress is difficult to control, include maximally effective antiemetics in first-line prophylactic antiemetic regimens so that rescue therapy will not be necessary. No clear evidence was provided on the most effective management of breakthrough or refractory CINV, and it is recommended that maximal prophylactic antiemetics are the best current approach.

The authors concluded that control of nausea and vomiting with high-dose chemotherapy remains a problem and more evidence is needed to aid researchers in making guideline decisions as to how to best manage CINV using modern antiemetics. Limited evidence is available for management of breakthrough and refractory CINV.

To evaluate the safety and efficacy of palonosetron plus dexamethasone for patients receiving multiple-day, highly emetogenic chemotherapy (HEC)

Patients received 0.25 mg IV palonosetron as an infusion 30 minutes before chemotherapy on days 1, 3, and 5 plus dexamethasone 20 mg IV on days 1 and 2, 8 mg orally twice daily on days 6 and 7, and 4 mg orally twice daily on day 8. Given the high receptor-binding affinity and prolonged half-life of palonosetron, this study involved alternate day dosing (days 1, 3, and 5 rather than days 1-3) combined with a standard dexamethasone regimen for multiple-day, cisplatin-based chemotherapy.

The study consisted of 41 patients with germ cell tumors.

This was a nonrandomized trial.

The following data was collected.

• Number of emetic episodes (vomiting and retching)
• Use of rescue medication
• Intensity and duration of nausea on a four-point Likert scale used for nausea intensity
• Evaluation of the effect of nausea on patients’ quality of life via the Osoba nausea module, which assesses five patient-rated items using a four-point scale
• Pharmacokinetic (PK) data

• Descriptive analysis showed complete response (CR) rates.
• The protocol prevented vomiting for most subjects at all timepoints of the study (days 1-9). The lowest percentage came at day 4 when 68% of patients reported no vomiting.
• Some protection against nausea was provided, with 59% or more of patients reporting no or, at maximum, mild nausea at any time on each study day.
• No severe adverse events were noted.
• The most common side effects were headache and constipation.
• No evidence of cumulative toxicity PK data was reported.

• The sample size was small.
• No control arm was included.
• This was a nonrandomized trial.

RESOURCE TYPE: Expert opinion

• DATABASES USED: None
• INCLUSION CRITERIA: None
• EXCLUSION CRITERIA: None

PHASE OF CARE: Active antitumor treatment

Review article

Literature review of common anti-PD-1 checkpoint pathway inhibitors/antibody therapy adverse events. No evidence of quality review provided.

Research is needed on the management of anti-PD-1 checkpoint pathway inhibitors/antibody therapy toxicities.

To investigate the effectiveness of corticosteroids for the treatment of fatigue in patients with advanced cancer

Patients were randomized to receive 16 mg methylprednisolone or placebo orally twice daily for seven days. Study assessments for quality of life levels were done at baseline, day 3, and day 8. Fatigue and appetite loss were evaluated daily.

• N = 34  
• MEDIAN AGE = 69 (range = 46–84 years)
• MALES: 61.8%, FEMALES: 38.2%
• KEY DISEASE CHARACTERISTICS: Multiple tumor types

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

• PHASE OF CARE: End-of-life care
• APPLICATIONS: Palliative care 

Double-blinded, placebo-controlled, randomized, controlled trial

• Visual Analog Scale (VAS) for fatigue and appetite loss
• Quality of Life Questionnaire for Cancer Patients treated with Anticancer Drugs (QOL-ACD)

Fatigue and appetite loss improved in both groups. On day 5, appetite was significantly better with steroid use (p = 0.011). There were no significant differences in adverse events between the groups.

The findings of this study demonstrate that this oral steroid may be helpful for anorexia, but it was not effective for reducing cancer-related fatigue.

• Small sample (< 100)

Oral corticosteroids may improve loss of appetite in patients with advanced cancer. However, steroids were not shown to be helpful in managing the cancer-related fatigue in this study.

To determine if the use of auricular acupressure is effective in relieving nausea and vomiting in patients with breast cancer who are receiving chemotherapy

Random assignment of patients: The experimental group received standard antiemetics for chemotherapy-induced nausea and vomiting (CINV) and auricular acupressure (AA) for five days. The control group received standard antiemetics only. Acute and delayed CINV was measured with the Morrow questionnaire daily for five days after receiving chemotherapy. The questionnaire has 16 items measured with a 7-degree Likert-type scale. Patients self-reported. For the second cycle of chemotherapy, the groups were switched.

• N = 48   
• AGE = 32–65 years
• MEAN AGE = 46.02 years
• FEMALES: 100%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Breast cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Use of anthracycline, cyclophosphamide, and taxane—high-risk for CINV

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

PHASE OF CARE: Active antitumor treatment

Crossover clinical trial

Morrow (Moro) questionnaire

• Number and intensity of nausea in acute and delayed phases in the AA group was significantly lower than in the control group (p < 0.001).
• The number and intensity of vomiting in the AA group was significantly lower (p < 0.005). 

The use of auricular acupressure was shown to help alleviate CINV when used along with standard antiemetics in patients with breast cancer receiving moderate to high-risk emetogenic chemotherapy.

• Small sample (< 100)
• Risk of bias (no blinding)
• The experimental group's and control group’s intervention was changed in the second cycle.

Auricular acupressure is a safe, noninvasive, easy, patient-administered, nursing-centered, nonpharmacologic treatment and was shown to lower the number and intensity of nausea in both the acute and delayed phases of treatment.