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.

To evaluate the efficacy of 1,000 mg fish oil capsules versus placebo of 1,000 mg olive oil capsules in a two-arm trial

A daily dose of 18 capsules was given over a two-week period. Dosage decreased to a minimum of six capsules daily secondary to intolerance. Mean eicosapentaenoic acid (EPA) dose was 1.8 g/day. Docosahexaenoic acid dose was 1.2 g/day.

• Eligibility requirements were presence of anorexia (> 3 on visual analog scale) plus weight loss (> 5% pre-illness weight), ability to maintain oral food intake over the course of study, normal cognition (using Mini-Mental State Score), written informed consent, and advanced cancer (locally recurrent or metastatic disease).
• Sample size was 91 patients at outset, then randomized to 45 for study and 46 for placebo. After attrition, 30 patients for both groups completed the study.

The two-site trial was conducted in the Acute Palliative Care Unit at Grey Nuns Hospital and the inpatient and outpatient areas at Cross Cancer Institute in Edmonton, Alberta, Canada.

A randomized, placebo-controlled, double-blinded trial design was used.

• Visual analog scale (VAS) used to measure appetite, nausea, tiredness, and well-being
• Anthropometric measures of height, weight, body composition, muscular circumference, and skinfolds done in the office on days 1 and 14
• Functional level measured with Karnofsky Performance Status Scale and the Edmonton Functional Assessment Tool
• Plasma phospholipids
• Nutritional intake diary

Five patients in each group left the study secondary to gastrointestinal intolerance. There was no significant difference in any of the subjective or objective parameters between the two groups. Both groups showed an equal trend toward improved appetite, –9.8 for the fish oil and –9.0 for the olive oil placebo on the VAS.

• Length of study was limited to two weeks. Period was based on previous megestrol acetate trial results and perceived need for short-term symptomatic amelioration.
• Original study design was altered secondary to gastrointestinal intolerance: 18 capsules down to a minimum of 6 capsules per day. There was variance in actual amounts taken.
• High attrition rate of 31% brings into question whether the original sample size was large enough and if the ultimate results were underpowered.
• Whether the lack of significant findings was due to a reduced dose of fish oil or because of the short duration of study is questionable.

To compare the effectiveness of oral methylprednisolone against placebo for relief of symptoms in patients with terminal cancer (pain, psychiatric status, appetite, nutritional status, and daily activity)

Participants were randomized to two groups, one receiving a placebo and the other receiving oral methylprednisolone (MP).

• Days 0–4: Participants received 16 mg of of oral MP or the placebo.
• Days 5–7: No treatment was given.
• Day 8: Crossover
• Days 8–12: Participants received oral MP versus placebo.
• Day 13: The double-blind was completed, then all participants received 32 mg of oral MP daily for 20 days.

Participants were evaluated in in the morning on days 0, 5, 13, and 33.

• The study reported on a sample of 40 patients.
• Patients were included if they were terminally ill with cancer, had not received anticancer therapy for four weeks prior to the study, and were not on medication except for analgesic mediation (propoxyphene compound).
• Patients were excluded if they had diabetes, infection, history of peptic ulcer disease, or severe psychiatric disturbances.

A randomized, double-blind, crossover trial design was used.

The following symptoms were measured.

• Pain
• Psychological status: Hamilton Rating Scales for depression (HAM-D) and anxiety (HAM-A) were used.
• Appetite: The mean amount of food eaten was measured. Patients evaluated themselves using a visual analog scale (VAS).
• Nutritional status: Daily weight, skinfold measurement, and serum albumin levels were monitored. 
• Activity: An interview was conducted with the nurse, participant, and family regarding the participant's ability to perform and engage in activities of daily living (ADL).

At the completion of the study, 31 participants were evaluated. They showed significant improvement in pain, depression, appetite, and food consumption. No improvement was noted in anxiety or performance status. 

No change in nutritional status was observed in either arm of the study. All parameters sensitive to MP reached maximum improvement during the first phase of the study. Eight of 23 participants who initially responded to MP were not experiencing symptomatic benefit from the drug by day 33.

The study suggested that short courses of corticosteroids can be given to severely symptomatic patients with advanced cancer who have no major contraindications.

• The study had a small sample size, but looked at a wide variety of symptoms experienced by patients with cancer at the end of life, not just appetite and food intake.
• The corticosteroids had side effects of cushingoid features, increased anxiety, and mild fluid retention.

To compare the risk of musculoskeletal injury in women with or at risk for lymphedema between a weight-lifting program and standard care

Women were randomized to receive twice weekly weight lifting or standard care for one year. Patients in both groups attend one hour of education on lymphedema. Women in the weight-lifting group received twice weekly group-based supervised instruction on proper biomechanics. Sessions lasted 90 minutes and included upper- and lower-body exercises and 10 minutes of aerobics and static stretching. If there were no changes in arm symptoms at a given weight, the weight was increased by 1 lb.  There was no upper limit on maximum weight lifted over one year. Patients with lymphedema wore a custom-fitted compression garment during exercise. Data were compared to weight-lifting injury rate data among a general population.

• The study sample (N = 243) was comprised of female patients with breast cancer.
• Mean age was 55.8 years.
• Time since cancer diagnosis ranged from 39–88 months.
• Fifty-nine percent of patients had stage I disease.
• Eight percent of patients were taking tamoxifen at the time of the study.
• The majority of patients had at least some college education and were White; 37% were Black.

The study took place in the eastern United States.

The study has clinical applicability for late effects and survivorship.

The study used a radonmized controlled trial design with epidemiological analysis comparison.

• Patients completed the International Physical Activity Questionnaire.
• Anthropometric measures were used.
• Strength measurements were taken.
• Patients were interviewed regarding adherence.
• Self-reported healthcare use rates were reported.
• Arm volume was measured via bioimpedence monthly.
• Cirumferences and water displacement volume were measured.

Strength was better in the weight-lifting group at 12 months compared to usual care controls (p = 0.03). Patients with lymphedema had greater odds of a musculoskeletal injury compared to controls (OR 19.9, 95% CI 5.1–77, p = 0.001). Patients at risk for lymphedema in the weight-lifting group did not have higher odds of injury. Injury rate per 1,000 reported exercise sessions among patients who did the weight-lifting was less than weight-lifting injury rates among a comparison group of premenopausal women. Six women in the weight-lifting group reported shoulder injuries, one had a wrist injury, and three had lower-body injury. Healthcare use in the control group was not reported.

Weight lifting in women with and at risk for lymphedema appears to be safe, with no more frequent injury rates than those seen in other women; however, musculoskeletal injuries did occur. This points to the need for supervision and communication with professional healthcare providers when delivering a weight-lifting program.

• The study has a risk of bias because no blinding was done.
• Measurement validity and reliability are questionable.
• No information about any changes in lymphedema were provided in the report (reported elsewhere with main study findings) and healthcare use data was only provided for patients who were involved in weight lifting. 
• Injury findings were not fully discussed, in terms of likelihood of being caused by weight lifting. The method of injury measurement was based on patient recall on a survey done at 12 months—patients may not have remembered all injuries. 
• It is not clear if patients adhered to schedule of weight lifting, and comparable activities in the control group were not described or discussed

Findings suggest that women with or at risk for lymphedema can safely do weight lifting, although, as with women without these problems, musculoskeletal injuries can occur. It appears that shoulder injuries were most common. These results point to the importance of supervision and monitoring by appropriate professionals during any weight-lifting program.

The intervention consisted of structured sessions that began with 20 minutes of conditioning exercises conducted by a physical therapist, followed by an educational session with cognitive-behavioral strategies for coping with cancer, and an open discussion with group leaders and other participants. Sessions were balanced with didactic material, a question and answer period, sharing, reflecting, relaxation, and physical activity. Participants attended eight sessions throughout the four weeks following enrollment. The intervention was delivered three days per week. After the fourth week, patients completed quality of life (QOL) questionnaires, and the questionnaires were collected at eight and 27 weeks after enrollment via mail.

• In total, 103 patients (66 male, 37 female) were included.
• Mean age was 59.6 years (range 31–85); 85.7% of patients were older than 50 years.
• The most common dominant disease status was gastrointestinal (36.7%).
• Of the participants, 59.2% were undergoing current chemotherapy, 77.6% were married, and 57.1% were currently employed.

Patients were included if they

• Were diagnosed within the past year
• Had an expected survival time of at least six months
• Had a treatment recommendation of radiation therapy of at least two weeks.

Patients were excluded if they had undergone previous radiation therapy, had recurrent disease after a disease-free period longer than 6 months, or had psychiatric disorders or active suicidality.

Division of Radiation Oncology, Mayo Clinic, Rochester, Minnesota

Patients were undergoing the active treatment phase of care.

The study was a randomized, stratified, two-group, controlled clinical trial and included a structured intervention arm (n = 49) and a standard medical care arm (n = 54).

• Linear Analogue Self Assessment (LASA)
• Profile of Mood States (POMS)
• Spielberger’s State-Trait Anxiety Inventory (STAI)
• Symptom Distress Scale (SDS)

The intervention had no significant impact on any fatigue measures between the groups. No significant differences were observed at baseline between the groups for fatigue. There were no significant differences in mean fatigue scores between the groups at any week.

The compliance of the patients after the sessions were completed is unknown.

To evaluate the effect of types of exercise on cancer-related fatigue.

Only randomized, controlled trials studying the outcome variable of cancer-related fatigue were included.

Seven thousand two hundred forty-five articles met the initial selection criteria. A final sample of 44 studies was included. Two independent raters collected data, and the intensity of exercise was estimated using metabolic equivalent units (METs).  MET values for a given exercise were coded from the Compendium of Physical Activity.

• The total number of participants across all studies was 3,245.
• Twenty-five studies exclusively reported breast cancer survivors.
• Mean age was 53.8 years.
• Forty-six percent of patients were undergoing active cancer treatment.

Characteristics of the Interventions

• Average length of exercise was 11.5 weeks (standard deviation [SD] = 5.2 weeks), and average intensity was 5.6 MET.
• Twenty-four studies included only aerobic exercise, six included only resistance exercise, 11 included a combination of resistance and aerobics, and six used neuromuscular exercise, such as yoga or tai chi.
• Ten studies used a theoretical base:  transtheoretical model of behavior change, self-efficacy, Roy adaptation model, Payne adaptation model, and the Levine conservation model.

Fatigue Measurement

• Fatigue was measured in 30% of patients with the Functional Assessment of Cancer Therapy (FACT) questionnaire, 20% with the Piper Fatigue Scale, 13% with the Profile of Mood States (POMS), 11% with the Brief Fatigue Inventory (BFI), 11% with the European Organisation for Research and Treatment of Cancer Quality of Life questionnaire (EORTC QOL-C30), and 4% with the linear analog scale.

Regression analysis was used to identify factors that were related to the degree of fatigue modulation.  Significant factors were

• Adherence to a theoretical model (p < 0.001)
• Sample of older cancer survivors (p = 0.04)
• Moderate intensity resistance exercise use (3–6 MET) (p = 0.01).

Session length and number of exercise sessions were not significantly related to effects on fatigue.

Overall effect size of fatigue modulation was 0.31 (95% confidence interval [0.22, 0.4]).  Effect size was 0.39 among survivors of breast cancer and 0.42 among survivors of prostate cancer.  In other cancer types, there were few studies and very small effects, but analysis demonstrated a consistent effect in favor of exercise.

Resistance exercise of moderate intensity appears to be the most effective in reducing cancer-related fatigue. This finding can be useful in planning exercise interventions as well as further research. The report stated a dose response effect on fatigue with exercise; however, the number and length of sessions was not a predictor of the degree of change in fatigue. These two findings seem to be contradictory. This aspect was not discussed by the authors.

The finding that resistance exercise interventions of moderate intensity were more effective than low-intensity or aerobic exercise is contrary to current National Comprehensive Cancer Network (NCCN) and American Cancer Society (ACS) guidelines, which do not mention resistance exercise and emphasize aerobic exercise. Moderate resistance exercise, such as weight machines, resistance bands, or free weights, may be a type that patients can maintain more easily. Use of theoretical models that incorporate issues of exercise behavior and behavior change may be more effective in providing support for the psychological components of adhering to an exercise program.