Patients received 20 mL pure, natural honey 14 minutes before radiotherapy, then 20 mL 15 minutes and six hours after radiotherapy. Honey was rinsed and gradually swallowed to coat the oral and pharyngeal mucosa.

• N (honey group) = 20
• N (control group [20 mL NS]) = 20
• KEY DISEASE CHARACTERISTICS: Patients with head and neck cancer received radiation to a total dose of 50–60 Gy.
   

• RCT
  • Single-blind (examiner only)

• Mucositis severity was scored each week of radiation by one clinician blinded to groups.
• Oral Mucositis Assessment Scale (OMAS)

OMAS scores were significantly lower for the honey group than the control group for all weeks (p = 0.000). Significant differences were noted during week six of therapy. Mean weight loss was significantly higher in the control group (p = 0.000).

• Small study

Bupropion sustained release (SR) was administered for four weeks at the maximum tolerated dose. Dosing was initiated at 100 mg in the morning and adjusted in increments of 50 mg, based on tolerability and effects, to a maximum of 300 mg daily. It was given in divided doses of either 100 or 150 mg. The dose was not increased if the maximum tolerable dose had been identified. The dose was 300 mg per day until the Brief Fatigue Inventory (BFI) score had dropped to less than 50% of the initial value. Following dose escalation, a four-week, fixed-dose phase occurred at the maximum tolerated dose, during which efficacy and safety measures were assessed every two weeks. The average dose for bupropion SR was 214 mg per day (standard deviation = 80 mg).

• The study included 21 patients (52% male) with a mean age of 40.4 years.
• All patients had persistent fatigue as a prominent symptom (scoring at least 4 out of 10 on the BFI fatigue interference scale). Nine patients scored 7 or greater on the BFI, which indicated severe fatigue.
• One-third of the patients had a primary brain tumor, and approximately 25% had breast cancer. Patients with brain tumors were overrepresented because the sample included a specific recruitment of this patient population.
• Patients were ineligible if they were receiving erythropoietin or had received it in the past six weeks, were using psychostimulants or antidepressants, or identified a medical cause for fatigue (e.g., thyroid dysfunction, adrenal insufficiency) on screening tests or on review of systems.

• Outpatient
• Large comprehensive cancer center

The study used a prospective, variable dose, open-label trial design.

• BFI scores were measured every two weeks and were used for dose escalation and then were measured twice for evaluation of treatment effects during the four-week, fixed-dose phase of the study.
• Other constructs measured included depression and health-related quality of life.

• A statistically significant improvement (p = 0.001) in fatigue was found when the baseline fatigue score was compared to the fatigue score obtained after four weeks of the fixed-dose treatment with bupropion.
• At baseline, fatigue and depression were not significantly correlated (r = 0.21).
• Four patients withdrew during treatment due to intolerable side effects (n = 1), perceived lack of efficacy (n = 2), and scheduled surgery for cholecystitis and cholelithiasis (n = 1).

• The trial was open-label and nonrandomized.
• The sample size was small, which made it difficult to establish a relationship between depression and fatigue.
• Overrepresentation of patients with brain tumors limited generalizability.
• The lengths of treatment and follow-up were brief.
• Side effects experienced at dose limits were not described; one patient withdrew because of side effects, but no details were reported.
• Cost was incurred to acquire the drug.

To determine the effect of n-acetyl cysteine (NAC) on the incidence and severity of oral mucositis glutathione peroxidase-1 activity

Patients were randomized to groups by a researcher not involved in the assessment of study outcomes. This same researcher also provided either the study drug or the placebo to the administrating nurse. Nurses were not blinded to the study groups, but treating physicians and those involved in the assessment of study data were blinded to the groups.

The study group was given NAC at 100 mg/kg of body weight diffused in 500 ml dextrose solution 5%. The drug was infused over a three-hour period beginning on the same day as high-dose chemotherapy (HDC) and continuing until 15 days post-transplantation. A placebo infusion was given to control subjects. Patients were assessed daily beginning the first day of HDC and continuing for 21 days post-transplantation or until mucositis resolved.

• N = 80
• AVERAGE AGE = 33.5 years
• MALES: 68.7%, FEMALES: 31.3%
• KEY DISEASE CHARACTERISTICS: Acute myeloid leukemia 51.3%, acute lymphoblastic leukemia 43.8%, and myelodysplastic syndrome 4.9%

• SITE: Single-site

PHASE OF CARE: Active antitumor treatment

Double-blind, randomized, placebo-controlled study

• World Health Organization (WHO) Oral Toxicity Scale

The overall incidence of all grades of oral mucositis (OM) did not differ between groups. The incidence of severe OM (grades 3 and 4) was significantly lower in the intervention group (23.7%) compared to the control group (45.2%) (p = 0.04). No patients in the intervention group developed grade 4 mucositis while seven patients in the control group developed grade 4 mucositis. Patients who received NAC had a significantly shorter duration of mucositis (6.24 days) compared to controls (8.12 days) (p = 0.02). There was no difference in the time to onset of mucositis between groups. The use of parenteral opioid analgesics was not significantly different between study groups.

In this study, patients in the intervention group experienced less severe oral mucositis. No patients who received NAC developed grade 4 mucositis. Additionally, patients receiving NAC had a shorter duration of oral mucositis compared to controls. There was, however, no difference in the overall incidence of all grades of mucositis (grades 0–4) and no difference in the time to onset of mucositis between groups.

• Small sample (< 100)

NAC was shown to decrease the severity and duration of OM and was well tolerated by the patients in this study. Patients undergoing transplant can benefit from these findings as the toxicities of increased pain, potential for infection, impaired nutritional intake, and prolonged hospitalization can be decreased. Nurses should carefully asses patients for the presence of mucositis during treatment with HDC and continue assessments until mucositis has resolved.

To test a telephone-based symptom management (TSM) intervention based on social cognitive theory with patients with lung cancer and their caregivers

The control group received education/support. The goal was to test the effect of TSM on the following patient symptoms: anxiety, pain, breathlessness, fatigue, and depressive symptoms. In caregivers, the focus was on anxiety and depressive symptoms. The intervention group dyads received TSM sessions (each was 45 minutes) for four weeks from a licensed social worker who was trained by a psychologist. The intervention involved giving participants instructions on symptom management, problem solving, cognitive restructuring, emotion focused/self-soothing, communication skills, pleasant activity scheduling, and activity pacing. Participants received identical handouts detailing the points discussed and practice assignment and a CD with instructions for relaxation exercises. The teaching was based on various EB cognitive behavioral and emotion-focused strategies. The sessions focused on both the patient and caregiver.

• N = 106 patient-caregiver dyads (intervention group = 51 dyads, control group = 55 dyads)   
• AGE RANGE = TSM group: 20–76 years, control group: 20–80 years
• MEAN AGe = TSM group: 56.33 years (SD = 14.09), control group: 56.75 years (SD = 13.81)
• MALES: 27%, FEMALES: 73% of caregivers
• CURRENT TREATMENT: Other
• KEY DISEASE CHARACTERISTICS: Caregivers of patients with small and non-small cell lung cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Dyads were fluent in English, primarily Caucasian, had 13 years of education, and had an average annual household income of $30,000. Sixty-three percent of the caregivers were spouses or partners of the patient. The only difference at baseline between the TSM group and education/support group was caregiver income.

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

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

• Randomized, controlled trial with the intervention group (TSM) compared to education/support group

Primary outcomes for the caregivers were:

• Generalized Anxiety Disorder 7-Item Scale (GAD-7) to assess caregiver anxiety symptoms
• The Patient Health Questionnaire-8 (PHQ-8) to assess for depressive symptoms

Secondary outcomes: 

• Kilbourn 8-items to assess self-efficacy in managing emotions
• Social Constraints Scale—5 items to assess perceived social constraints on cancer-related disclosure from the other dyad member

No significant main effects were found for primary outcomes for either patients or caregivers. Small effect size improvement in self-efficacy of caregivers managing their own emotions was observed in the TSM group, while it declined slightly in the education/support group. Also, caregivers in the TSM group reported less perceived social constraints compared to the education/support group. No main effects were noticed in caregivers' self-efficacy in relation to managing patients’ symptoms.

The intervention did not demonstrate a significant effect.

• Small sample (< 100)
• Risk of bias (no appropriate attentional control condition)
• Key sample group differences that could influence results
• Intervention expensive, impractical, or training needs
• Subject withdrawals ≥ 10%  
• The intervention included multiple components, so pinpointing cause and effect was difficult.

The effect of a nonpharmacological (psychosocial) intervention on the symptoms of patients with lung cancer and their caregivers is inconclusive. Psychosocial interventions improved caregivers’ self-efficacy in managing their emotions and perception of social constraints.

To examine the health effects—on existential and psychological well-being, fatigue, and sleep—of writing about the deepest cancer-related thoughts and feelings in patients with advanced breast cancer.

• By telephone, one week after the screening assessment, investigators conducted a baseline interview of patients who met the criteria. Investigators obtained consents.
• At random, a computer assigned patients to the expressive writing or neutral writing group. Patients were stratified by ethnicity and age.
• Patients received four sets of writing instructions, lined paper, forms for rating the essays, and envelopes for returning the materials by postal mail.
• Study design called for each patient to complete four writing sessions over a period of four to seven weeks, with instructions for each session provided by telephone by the study staff. Intervention and control groups were to begin writing immediately after the instruction telephone call. All patients were to write for 20 minutes continuously. At the 20-minute mark, a telephone call from staff collected patients' assessments of the quality of the writing time; adjustments were made for interruptions. Staff told patients to rate their essays on a scale of one to seven and asked patients to mail their essays to the investigators.

• The study reported a sample of 86 females with stage IV breast cancer.
• Mean age was 57.4 years (standard deviation [SD] = 12.5 years) in the expressive writing group and 58.5 years (SD = 11.7 years) in  the neutral writing group.
• Patients were included if they had clinically elevated distress, as indicated by scores greater than four on the Distress Thermometer, were fluent in English, and were 18 years or older.
• Patients were excluded from the study if they had severe cognitive impairment, as assessed by the Short Portable Mental Status Questionnaire, or if they were already engaged in expressive writing on a daily basis.
• Average range of time since diagnosis was 4.2 to 4.7 years in the expressive writing group and 3 to 3.5 years in the neutral writing group. Most patients had received chemotherapy or hormone therapy.
• Of the patients in the expressive writing group, 40.9% were using mental health services at baseline.

• Single site
• Outpatient setting
• Comprehensive cancer center in New York City

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

The study was a randomized trial, with interviewers blinded in regard to the group they were interviewing.

• Meaning/Peace subscale of the Functional Assessment of Chronic Illness Therapy (FACIT)–Spiritual Well-Being Scale, to assess existential well-being. This measure reflected patients’ degree of purpose in life and inner peace.
• A measure of demoralization, or existential despair and distress
• Distress Thermometer, to measure psychological well-being and general distress
• Center for Epidemiologic Studies Depression (CESD) Scale, to assess symptoms of depression
• Anxiety subscale of the Hospital Anxiety and Depression Scale (HADS), to measure anxiety
• Pittsburgh Sleep Quality Index (PSQI), to measure habitual sleep disturbance and fatigue over one month. This study used the total global sleep-quality score.
• Fatigue subscale of the FACIT, to measure fatigue during the past seven days 
• Australia-modified Karnofsky Performance Status (KPS) Score, to measure sociodemographic and medical variables and functional impairment at baseline. Trained interviewers administered this instrument.
• Manipulation check and essay ratings, gathered by an independent rater blinded to the group assignment, to assess the writing instructions for each essay
• Seven-point scale, used by each patient, to rate how personal the patient's essays were and how much essays revealed of emotions
• Linguistic Inquiry and Word Count, a computerized text-analysis program, to report the percentage of position and negative-emotion words in each essay

In this sample, expressive writing—compared to neutral writing—did not result in better existential and psychological well-being, reduced fatigue, or enhanced sleep quality. Although both writing groups showed little change in their distress over time, during the study, patients in the expressive writing group reported more than double the rate of mental health service use than did patients in the neutral writing group.

Expressive writing may have increased patients’ awareness of their distress and challenging circumstances, prompting the patients to seek mental health services. Further research is needed.

• The study had a small sample size, with less than 100 patients.
• Patients who were younger and closer to diagnosis were more likely to participate; however, these response biases were relatively small.
• Whether results are generalizable to men and patients with diverse ethnic and socioeconomic backgrounds are points that warrant examination.
• The study relied on self-reported outcome measures administered at one follow-up assessment.

Expressive writing may increase use of psychological support services by distressed patients, without increasing symptom severity. Expressive writing may help keep patients in touch with their emotions, whether negative or positive. When patients are in touch with their emotions, they may be more likely to reach out for help, if they recognize negative emotions that they are not resolving on their own. However, this intervention did not result in differences in patient symptoms or outcomes.

STUDY PURPOSE: To review the common conservative therapies for arm lymphedema secondary to breast cancer treatment

• Complex physical therapy 
• Manual lymphatic drainage 
• Pneumatic pump therapy 
• Oral pharmaceuticals 
• Low-level laser 
• Limb exercise
• Limb elevations
• Self-massage 

DATABASES USED: Search of English literature using the search engines CINAHL, PubMed, MEDLINE, CancerLit, PEDro, and Cochrane Evidence-Based Medicine Database; proceedings from the International Society of Lymphology and the Australian Lymphoedema Association; and contact with primary authors when publications were difficult to source. 

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Data were extracted using EndNote 7^® (Thomson Reuters), and a quality scale assessment tool was used. Review included randomized, controlled, parallel, crossover format, and case-controlled and cohort studies. Case reports and anecdotal evidence were not reviewed. Because of treatment and data heterogeneity, authors were not able to perform a meta-analysis.

• Manual lymphatic drainage and compression: 43%
• CPT: 28%
• Compression: 12% (not rated as stand-alone therapy)

• Low-level laser: 12% therapy 
• Manual lymphatic drainage alone: 24%

• Exercise: 5%

• Pneumatic pump: 27%
• Self-massage: 3%

• Drugs (benzopyrones): 16%
• Elevation: 3% (not rated as stand-alone therapy)

• Limited sample size in many studies and few randomized, controlled trials

To document the use of methadone as part of an opioid-rotation strategy for the treatment of uncontrolled pain in patients with delirium at the end of life

Ten patients rotated from morphine, five from fentanyl, two from hydromorphone, and three from fentanyl-morphine or morphine- hydromorphone combinations. Authors were purposefully conservative in calculating the starting methadone dose. Within the first week four patients expired, one changed to IV methadone, and two rotated back to morphine because of worsening delirium and inadequate analgesia. At two weeks, 10 patients had expired. Of the remaining 10, seven stayed on methadone. The average dose was 1.1 mg/hour. Two patients returned to morphine, and one was rotated to Percocet.

• The sample was composed of 20 patients with cancer who were experiencing severe pain and delirium at the end of life and whose delirium did not resolve 24 hours after administration of a neuroleptic.
• The age range of patients was 47–77 years.
• Ten males and 10 females participated in the study.
• The study included patients with a variety of cancer diagnoses.

United States

Nonrandomized open-label prospective study

• Numeric analog scale (NAS), to measure pain
• Scale, 0–3, to measure sedation
• Memorial Delirium Assessment Scale (MDAS)
• Opioid dose

Pain control was significant in 15 of 20 patients; average analgesia was good to excellent. Sedation rating decreased from 1.65 to 0.55 on 1–3 scale. Cognitive status improved for nine patients. Six patients achieved moderate improvement in cognitive status; two, partial improvement; and three, no improvement. Three days after the switch from an opiod, average MDAS score improved from 23.6 to 10.6. Decreased alertness on methadone was devoid of agitation.

Methadone can be an acceptable alternative to an opioid in the treatment of refractory pain and terminal delirium. The use of methadone can minimize the need for sedation to treat delirium.

• The study had a small sample. Sample size decreased as patients expired.
• Authors did not specify the process of converting from an opioid to methadone.
• Many patients must be rotated to a different drug.

To evaluate the effectiveness of oral pyridoxine for preventing and treating palmar plantar erythrodysesthesia (PPE) associated with capecitabine

Of the patients receiving oral pyridoxine, 73 patients (74%) received it as prophylaxis, and the remainder (26%) received it as acute hand-foot syndrome (HFS) treatment. The median dose of pyridoxine was 200 mg/m².

• N = 198–99 patients who were receiving capecitabine and pyridoxine and 99 patients who were receiving capecitabine and no pyridoxine

• SITE: Multi-site
• SETTING TYPE: Outpatient centers
• LOCATION: Sentara Cancer Institute in Norfolk, VA

• Retrospective review of 198 charts

• National Cancer Institute Common Toxicity Criteria version 2.0

The data did not support that vitamin B₆ prophylaxis prevented overall PPE incidence in a greater proportion of patients compared with those who did not receive prophylaxis (60% versus 53%). However, when used as treatment, a greater proportion of patients receiving vitamin B₆ reported symptom improvement (65% versus 12%, p < 0.001).

Pyridoxine is not recommended for prophylaxis but may provide some relief for patients with acute HFS.

• The data was obtained from chart review, which is subject to documentation bias and patient selection.
• This was not a controlled trial.
• A controlled trial of Xeloda^® with and without vitamin B₆ seems warranted.

Patients were given oral paroxetine 20 mg orally daily or placebo for eight weeks.

• In total, 479 patients (paroxetine, n = 244; placebo, n = 235) were included.
• Mean age was 56.5 years (standard deviation = 12.6 years) (range 27–87).
• Most of the patients were female, 90% were Caucasian, 57% had breast cancer, and 14% had lung cancer.
• All patients were receiving cyclic chemotherapy (but not concurrent with radiotherapy or interferon).

18 Community Clinical Oncology Program (CCOP) outpatient centers

Patients were undergoing the active treatment phase of care.

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

• Fatigue Symptom Checklist (FSCL)
• Multidimensional Assessment of Fatigue (MAF) (Question 1 only)
• Monopolar Profile of Mood States (POMS) Short Form Fatigue/Inertia subscale

The paroxetine group and the placebo control had comparable levels of fatigue and depression at study inception. Paroxetine had neither beneficial nor detrimental effects on fatigue. There was a significantly lower mean level of depression in the paroxetine group compared with the placebo group. Treatment with paroxetine also favorably affected patients’ general moods. There were no differences in the effect of paroxetine on fatigue by gender, age, indication for treatment (adjuvant treatment versus treatment for metastatic disease), or by whether patients were more or less fatigued at baseline.

• Whether the paroxetine group and the placebo control group had comparable hemoglobin levels at study inception is unknown.
• Less than .01% (n = 2) of the patients in the paroxetine arm experienced adverse events (skin rash and pulmonary embolus) that were possibly related to the study medication.

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

To compare the efficacy and safety of palonosetron with older 5HT3 receptor antagonists (RAs) in preventing chemotherapy-induced nausea

• N = 1,132 (MEC), 1,781 (HEC)
• MEAN AGE = 54.9 years (study 1), 54.4 years (study 2), 55.5 years (study 3), and 56 years (study 4)
• MALES: 22.8% (study 1); 23.1% (study 2); 44.7% (study 3); 44% (study 4), FEMALES: 77.2% (study 1); 76.9% (study 2); 55.3% (study 3), 56% (study 4)
• KEY DISEASE CHARACTERISTICS: Breast, lung, colorectal, ovarian, and gastric cancers and Hodgkin disease; included naïve and not naïve patients 
• OTHER KEY SAMPLE CHARACTERISTICS: Steroids were allowed. Alcohol and tobacco use were tracked.

• SITE: Multi-site
• SETTING TYPE: Multiple settings
• LOCATION: Studies that occurred in Europe or North America

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

Data were pooled from four studies that were multicenter, randomized, double-blinded clinical trials comparing palonosetron, ondansetron, dolasetron, or granisetron.

• Nausea (complete control, nausea-free rates, nausea severity, and use of rescue medication over five days following chemotherapy)
• Nausea and vomiting assessments were done by phone or during clinic visits. Patients were to document all episodes of emesis and nausea, the severity of nausea, and the use of rescue medication in their dairies for five days following chemotherapy.
• A nausea severity four-point categorical scale was used.

The patients treated with palonosetron experienced less nausea each day then the other 5HT3 RAs, and fewer patients receiving palonosetron had moderate to severe nausea. The use of rescue medication was less frequent among patients in the palonosetron arm. The complete control rates for palonosetron versus older 5HT3 RAs were 66% versus 63% during the acute acute phase, 52% versus 42% in the delayed phase, and 46% versus 37% in the overall phase. No safety differences or concerns were noted.

Palonosetron was more effective in treating and preventing nausea than ondansetron, dolasetron, and granisetron. All four agents tolerated equally well.

• Per the authors, the analysis included summarized data but was not powered for statistical comparisons between the agents.
• Nausea is subjective. The reliability may be influenced by the data collector.  
• NK1, which is a standard practice medication, was not used for HEC.

Nurses are aware that palonosetron has a longer half-life and is the medication of choice for outpatient treatment. This study reinforces palonosetron use by noting that more patients receiving it had nausea-free days, lower nausea ratings, and less rescue medication use. Nausea is very subjective, but nurses are aware that it is more of a problem in the delayed phase than actual vomiting. Nausea affects quality of life, and this study can help nurses choose the correct 5HT3 RA.