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.

The objective of the study is to assess oxygen therapy in patients with cancer.

Patients received two courses of oxygen at 5 L per minute and two courses of room air at 5 L per minute. Patients were randomized to either air or oxygen and then crossed over to the other treatment.

The study reported on a sample of 14 patients with hypoxemic dyspnea caused by advanced cancer previously treated with supplemental oxygen. Patients had normal cognitive function (MMSE score of at least 24/30) and hypoxemia (oxygen saturation less than 90% when patients breathed room air for more than five minutes). All were receiving oxygen via nasal cannula at 4 L per minute.

The study was a prospective, crossover, double-blind trial.

A baseline assessment occurred after 30 minutes of bed rest and a minimum of 5 minutes of stable oxygen saturation on room air. Dyspnea was assessed with VAS (0 = none to 100 = most). RR was measured for one minute twice; the results were averaged and assigned a score of 1–4 for RR. Patients made blind choices as to which treatment was most beneficial. Pulse oximetry evaluations also were recorded.

Oxygen saturation, respiratory rate and effort, and VAS were significantly better on oxygen (p < 0.0001). Researchers concluded that oxygen is beneficial to patients with hypoxia and dyspnea at rest.

• The study had a small sample size.
• The taste or smell of oxygen experienced by patients was not mentioned.
• The validity of the double-blind design is questioned.

To compare subcutaneous (SC) injection versus nebulized morphine (median dose of 45 mg, equal to half of the scheduled equivalent opioid dose) on two separate days; because nebulized morphine is thought to have rapid onset of action and low systemic absorption, adverse effects may be avoided.

• The sample was comprised of 11 patients. 
• Median age was 58 years.
• Patients were included if they
  • Had dyspnea (at least 3 on a scale of 0–10 in which 10 = worst dyspnea not related to acute complication) and advanced cancer with no clinical evidence of bronchospasm (predominant restrictive ventilation)
  • Were receiving regular oral or parenteral opioids
  • Had normal cognition.

The study used a double-blind, randomized crossover trial design.

• Dyspnea self-reports on a 0–10 scale were measured at baseline (end of one hour of rest) and every 15 minutes for 1.5 hours and then every 30 minutes for the next three hours.
• The main outcome was dyspnea score at 60 minutes.
• Blind preference of treatment was assessed by patients and investigators.

Significant improvement occurred in dyspnea scores from baseline to 60 minutes measured at 15-minute intervals for both SC (dyspnea score decreased from 5 to 3; p = 0.025) and nebulized morphine (dyspnea score decreased from 4 to 2; p = 0.007). No significant difference was found between SC and nebulized morphine for each time period. Bronchospasm was not observed in the nebulized treatment group.

Both routes were effective in this sample. The number of patients was insufficient to determine a difference between the routes.

• The study had a very small sample size and insufficient power to rule out a significant difference between the two routes.
• Recruiting patients with continuous dyspnea (at rest) was very difficult.

The objective of this study was to assess the effect of one dose of subcutaneous (SC) morphine on dyspnea in patients with terminal cancer.

Patients were given 2.5 times their regular dose of morphine, administered at the time of their scheduled analgesic dose. In five patients who were not receiving opioids, the dose was 5 mg of morphine. The average dose administered was 22–28 mg.

The study reported on a sample of 20 consecutive patients with terminal cancer; all patients had severe dyspnea at rest because of restrictive respiratory failure.

The study was conducted on a palliative care unit.

The study was an open, uncontrolled trial.

• Dyspnea visual analog scale (VAS) and pain VAS were measured before the dose and every 15 minutes for 150 minutes.
• Respiratory rate, respiratory effort, arterial oxygen saturation (SO₂), and end-tidal arterial carbon dioxide pressure (PaCO₂) were determined before and 45 minutes after SC morphine.

• A statistically significant improvement in dyspnea was seen without any significant change in respiratory rate, respiratory effort, oxygen saturation, or PaCO₂.
• In patients with pain, the effect of morphine on dyspnea had a shorter duration than the analgesic effect.
• Toxicity was minimal and consisted of nausea.
• Of 20 patients, 19 reported improved dyspnea after SC morphine and continued to receive the same dose for dyspnea on an as-needed basis with continued relief.
• Authors suggest the need for confirmation with a double-blind study.

The study had a small sample size.

This study was conducted to assess the effects of methylphenidate (MPH) on neuropsychological functions for patients with cancer on continuous subcutaneous (SQ) infusion of narcotics for pain.

Participants were assessed immediately before and two hours after dose for two days.

• The total number of participants was 20. Nineteen were used in data analyses.
• The average participant age was 55 ± 12 years
• 60% of participants were male and 40% were female. 
• Participants had varied solid tumors, including lung, gastrointestinal, breast, prostate, and ovarian cancer.
• Participants were required to have received narcotics for at least five days before admittance to the study.
• No rescue doses were given to participants during the time frame of 7–10 am.

The study took place at Edmonton General Hospital in Alberta, Canada.

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

• Finger Tapping Test for motor function
• 20-item arithmetic test (5 questions each on addition, subtraction, multiplication, and division)
• Reverse Memory of Digits—attention Visual memory (VM) for attention and visual memory
• Subjective interview in which patients described which treatment helped more with confusion and sleepiness
• Edmonton Staging System for Cancer Pain (Stage I, II, III) Visual Analogue Scale for pain, nausea, drowsiness, confusion, depression, and activity

Significant improvement was noted in drowsiness, confusion, tapping speed, arithmetic skills, reverse digits, and visual memory (p < 0.001). Patients and investigators blindly chose MPH as more effective over the placebo in 13 of 14 cases.

In patients with cancer who had significant pain, immediate improvements in alertness, attention, and memory were noted. 

• The study had a small sample size.
• There was no control group as a comparison.
• No temporal level was provided of how long the MPH treatment would be beneficial.
• The study displayed limited cognitive assessment and lack of follow-up.
• The study was limited to patients on stable narcotic infusion.

Patients received 100 mg of thalidomide by mouth at night for 10 days. If improvement was shown, patients could continue.

• A total of 72 patients entered the study; 37 were evaluable.
• Patients were eligible for study if they
  • Had metastatic cancer
  • Were not receiving antineoplastic therapy
  • Experienced weight loss of more than 5% of usual weight
  • Had a life expectancy of more than two weeks
  • Had normal cognition
  • Were postmenopausal or had no possibility of becoming pregnant; men could not have sexual activity with women who could become pregnant.

This was an open-label study.

• Visual analog scale measuring
  • Difficulty falling asleep
  • Morning restedness
  • Insomnia
  • Nausea
  • Appetite
  • Sensation of well-being
• Caloric intake form

More than 30% improvement in symptom intensity was observed in the following parameters: difficulty falling asleep (17/35 = 49%), morning restedness (23/36 = 64%), insomnia (22/32 = 69%), nausea (16/36 = 44%), appetite (22/35 = 63%), and well-being (18/34 = 53%). Twenty-seven patients completed food intake forms on days 1 and 10. Caloric intake increased from 1,325 to 1,531 calories per day (p = 0.047). Three patients discontinued thalidomide because of adverse effects: dizziness (1) and drowsiness (2).

• The study had a high attrition rate and poor compliance, possibly because of survival expectations of only more than 2 weeks.
• The study was open and subject to bias.

Findings need to be confirmed in double-blind studies.