To evaluate the efficacy of Wisconsin ginseng on cancer-related fatigue (CRF).

2,000 mg of Wisconsin ginseng or placebo BID (breakfast and lunch) over eight weeks. The assessment conducted at baseline and at four and eight weeks.

• N = 364
• MEAN AGE = 55.3 years for the ginseng group, 55.9 for the placebo group
• MALES: 19% in ginseng group and 25% in placebo group, FEMALES: 81% in ginseng group and 75% in placebo group         
• KEY DISEASE CHARACTERISTICS: Primarily breast (64% in ginseng and 57% in placebo groups) but included colon, prostate, hematologic, gynecologic, and combination/unknown/other cancers having completed or receiving curative intent therapy within past two years and who scored a minimum of 4 on 11-point scale that was present at least a month prior to study entry.
• OTHER KEY SAMPLE CHARACTERISTICS: Some were on active treatment during the study and some were post-cancer treatment.

• SITE: Multi-site  
• SETTING TYPE: Not specified  
• LOCATION: Mostly community cancer centers; location not specified

• PHASE OF CARE: Multiple phases of care

• Randomized, double-blind trial

• Multidimensional Fatigue Symptom Inventory–Short Form (general subscale)
• Profile of Mood States (fatigue-inertia and vigor-activity subscales)
• Brief Fatigue Inventory
• CTCAE (version not specified)

Statistically significant changes in scores for MFSI-SF between ginseng and placebo groups at four and eight weeks was in favor of ginseng, but only among those in active treatment. No differences in BFI scores were noted. Greater benefit reported among patients receiving active cancer treatment versus those who had completed treatment.

The ginseng group had improvements in fatigue scores over four- and eight-week periods without significant toxicities. However, data lacking on selected drug-ginseng interactions.

• Selective outcomes reporting
• Subject withdrawals ≥ 10%

Supports use of (controlled, manufactured) Wisconsin ginseng to modify CRF; however, more research is needed to determine how to maximize positive effects. It appears that ginseng effects may only be seen during active treatment.

Evaluate ginkgo biloba for the prevention of cognitive decline associated with adjuvant treatment for breast cancer

Patients were randomized to receive 60 mg of ginkgo biloba or a matching placebo twice a day starting before the second cycle of thermotherapy and continuing throughout treatment and 1 month beyond chemotherapy completion. Participants were stratified by type of chemotherapy, age, menopausal status, and lymph node involvement. Data were collected at baseline before the first or second chemotherapy cycle, during chemotherapy, at the first visit after chemotherapy (1 month), and at 6, 12, 18, and 24 months post-chemotherapy.

• A total of 210 participants were enrolled in the study.
• The median age was 50 years.
• The sample was 100% female.
• All participants had newly diagnosed breast cancer and were chemotherapy naïve. 
• All were receiving adjuvant chemotherapy. About 80% were receiving doxorubicin/cyclophosphamide with or without taxanes.
• 42% of the women were post-menopausal. 
• 94% of the women were Caucasian.

• Multi-site  
• Outpatient 
• 23 institutions in the United States

Participants were receiving active antitumor treatment.

Double-blind, randomized, placebo-controlled study

• High-Sensitivity Cognitive Screen (HSCS)
• Profile of Mood States (POMS)
• Cognitive subscale of the Perceived Health Scale (PHS)
• Common Terminology Criteria for Adverse Events (CTCAE) grading of adverse events
• Trail Making Test (TMT) A and B

No significant differences were seen between groups over 24 months in any study measures. All cognitive test scores improved from baseline to the first chemotherapy follow-up and then stabilized.

The study does not support the use of ginkgo biloba for prevention of cognitive impairment resulting from chemotherapy treatment in women with breast cancer.

• A risk of bias existed because of the very homogenous sample.
• The measurement validity and reliability was questionable because use of the same cognitive measures repeatedly could have resulted in improvement from practice effects.

Findings do not support the use of ginkgo biloba to prevent cognitive changes resulting from chemotherapy in patients with breast cancer.

To compare gabapentin to a placebo on three factors: efficacy in decreasing CINV, tolerability to the medication, and impact on quality of life.

• Day 1: 20 mg of dexamethasone and a 5HT3 receptor antagonist
• Days 2 and 3: 8 mg of dexamethasone two times per day with or without a 5HT3 receptor antagonist
• Day 4: 4 mg of dexamethasone two times per day with or without a 5HT3 receptor antagonist

• Day 1: One tablet (300 mg gabapentin/placebo) in the evening
• Days 2 and 3: One tablet (300 mg gabapentin/placebo) two times per day
• Days 4 and 5: One tablet (300 mg gabapentin/placebo) two times per day or three times per day

• N = 413
• AGE ≥ 50 years (73% in the gabapentin arm, 72% in the placebo arm)
• MALES: 30%, FEMALES: 70%
• KEY DISEASE CHARACTERISTICS: Breast, lung, colorectal, gynecologic, and hematologic cancers among others
• OTHER KEY SAMPLE CHARACTERISTICS: Performance status of 0–2, chemotherapy naive for highly emetogenic and moderately emetogenic chemotherapy; able to swallow pills; first cycle of chemotherapy

• SITE: Multi-site    
• SETTING TYPE: Outpatient    
• LOCATION: United States

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Palliative care

This phase 3 study was a placebo-controlled trial that was randomized and double-blinded.

• The patients kept a nausea and vomiting diary
• Numeric analog scales were used daily to measure average level of nausea, worst level of nausea, treatment satisfaction, and distress.
• The use of any rescue medications were recorded.
• Satisfaction with treatment and distress were recorded using a numeric analog scale.
• National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) to grade edema, somnolence, dizziness, and ataxia
• Patients used a self-report analog scale to measure loss of appetite, mood swings, diarrhea, fatigue, impaired concentration, and drowsiness.
• Functional Living Index-Emesis (FLIE)

This study did not support the effectiveness of gabapentin as prophylaxis for delayed chemotherapy-induced nausea and vomiting when used in conjunction with dexamethasone and a 5HT3 receptor antagonist.

• Risk of bias (sample characteristics)
• Findings not generalizable
• Other limitations/explanation: The authors defined highly emetogenic chemotherapy as a cisplatin-based regimen; however, several other chemotherapies are also highly emetogenic. Because the authors did not include all high-risk chemotherapies, the sample characteristics may be biased and the findings may not be generalizable to other highly emetogenic chemotherapies.

Based on this study, gabapentin is not recommended as prophylaxis for delayed chemotherapy-induced nausea and vomiting.

To determine whether any of three specific doses of American ginseng help cancer-related fatigue, as well as to evaluate toxicity.

Patients were randomized to receive ginseng doses of 750, 1,000, or 2,000 mg per day or placebo. Doses were given in twice daily dosing over eight weeks. The ginseng used was Wisconsin ginseng that met quality-control requirements for pesticides and contaminants. Specific description of ginsenosides content is described. 

Outcome measures were obtained at baseline, four weeks, and eight weeks. Patients were stratified according to stage of disease, gender, baseline fatigue score, and current treatment. Randomization assignments were computer-generated using a dynamic allocation procedure for distribution of stratification factors.

• In total, 175 patients (66% female) with a history of chronic fatigue completed the study. 
• Mean age across study groups ranged from 58 to 62 years (standard deviation [SD] = 12).
• Patient diagnoses were predominantly breast, colon, and lung cancer.
• Of the patients, 62% had stage III/IV disease.
• Of the patients, 71% had a baseline fatigue score of 4 to 7.
• Of the patients, 65% had previous chemotherapy.
• Of the patients, 57% were receiving current chemotherapy and 18% were receiving current radiotherapy.
• No significant differences existed between groups in demographic, disease, or treatment characteristics.

This was a multisite collaborative trial of the North Central Cancer Treatment group and the Mayo Clinic.

This was a randomized, double-blind, placebo-controlled study.

• Brief Fatigue Inventory (BFI)
• Vitality subscale of the Medical Outcome Scale (MOS) Short Form (SF-36)
• Global Impression of Benefit Scale
• Pittsburgh Sleep Quality Index (PSQI)
• Global Impression of Change
• Linear Analogue Scale
• Toxicities were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0 (NCI CTCAE)
• Patients completed weekly self reports of toxicities in a symptom experience diary to rate side effects on a 0 to 10 scale, with higher scores indicating greater severity.

• Mean scores for the SF-36 subscale between collective ginseng arms and placebo were not significantly different. A trend was observed for greater positive effects at the highest ginseng dose.
• Analysis of change in fatigue showed a greater effect on fatigue with the highest two dose groups, but this was not statistically significant.
• A trend was observed for greatest effect on quality of life measures at the highest ginseng doses.
• The greatest PSQI improvement over time occurred in the placebo group.
• Patient subjective perception of benefits showed an overall trend of higher benefit in the two highest ginseng dosage groups.
• No significant toxicities were associated with the use of ginseng.

Findings suggest that ginseng at the dose of 750 mg per day did not provide any benefit over that of placebo. At the two highest doses of ginseng, a trend was observed of decreased fatigue compared to placebo.

• The study was powered as a pilot study to evaluate composite ginseng dose groups versus placebo, so dose-related findings were underpowered to show statistical significance. 
• A challenge in studying herbal supplements is the lack of standardization and variability in content affected by growing conditions, so the findings may not be generalizable to use of ginseng grown elsewhere or under different climactic conditions.

The preliminary evidence here suggests that the improvement in patient perception with ginseng versus placebo is that this effect may have broad benefit to patients, even if objective measures of outcomes are nonsignificant. It would be worthwhile to more clearly and definitively evaluate the benefits of ginseng in additional larger, more definitive clinical trials.

To explore the effectiveness of psycho-oncologic interventions for patients and partners on anxiety, depression, psychopathology, and distress

Patients and partners who had been referred for psycho-oncologic service were recruited. Common interventions were psychoeducation, cognitive restructuring, behavior control techniques, guided imagery, relaxation, couples communication training, and other types of counseling in an individualized, nonstandard fashion. Patients and partners were grouped according to propensity scores calculated from variables shown to be significant in regression analysis for outcomes of interest, including gender, age, cancer site, stage of disease, baseline anxiety, and depression. Propensity matched control patients, and partners who did not receive the intervention were identified and used as control comparisons. Analysis was done in groupings according to the level of distress with propensity scores as low-, moderate-, or high-distress.

• N = 66 patients and 45 partners in ITT analysis; 43 patients and 27 partners completed the study  
• MEAN AGE = 57.8 years (SD = 14.2 years) for patients, 56 years (SD = 14.4 years) for partners in the intervention
• MALES: 60.6% for patients, 26.1% for partners; FEMALES: 39.4% for patients, 73.9% for partners
• KEY DISEASE CHARACTERISTICS: Multiple tumor types—hematologic, head and neck, and gastrointestinal most common; 63.6% of patients had stage 3 or 4 disease; 69.5% of partners were involved with stage 3–4 disease
• OTHER KEY SAMPLE CHARACTERISTICS: In most areas, patients in the control group did not have significant differences from those in the treatment groups. However, the majority of patients in the control group were highly educated, with 24% at the university level. Educational characteristics of patients and partners in the intervention group were not reported. Note: Sample characteristics are those who were moderately distressed. All characteristics of the full sample across all groups are not clearly provided.

• SITE: Single site  
• SETTING TYPE: Outpatient  
• LOCATION: Germany

• PHASE OF CARE: Multiple phases of care
• APPLICATIONS: Palliative care 

• Naturalistic design
  • Quasi-experimental with matched control comparison

• Hospital Anxiety and Depression Scale (HADS)
• Symptom checklist (nine psychological symptoms)
• Global Severity Index for overall psychopathology

Time effects within patient groups showed significant decreases over time in depression and distress (p ≤ .05), but not for anxiety and psychopathology. No group effects were seen on outcomes over time. Among partners, no changes were seen over time and no significant effects of the intervention were seen on outcomes. The same pattern was seen in completer and intent to treat analysis. Pre- and post-intervention data showed that patients had significant declines in anxiety (effect size Cohen’s d = 0.32, p = .01), distress (d = .46, p = .001), and depression (d = 0.52, p = .001) at 12 months, and partners had significant declines in anxiety (d = 0.45, p = .01) and distress (d = .42, p = .02) within the highly distressed group. No significant differences were seen in the less distressed group over time.

Findings suggest that psychotherapeutic interventions can reduce anxiety, distress, and depression among patients and partners who are highly distressed. Little benefit may exist for individuals who are less anxious or distressed at baseline.

• Small sample (less than 100)
• Baseline sample/group differences of import
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Measurement/methods not well described
• Questionable protocol fidelity
• Other limitations/explanation: Distress measurement and definition are not described. The matched controls were not completely described but were highly educated; the education level of the comparison group is unknown. The intervention was not standardized or reviewed for content, so one cannot determine the similarities or dissimilarities of intervention sessions.

Psychotherapeutic interventions may be beneficial for patients and caregivers who are highly distressed. Nurses need to be aware of the overall level of patient and caregiver distress and identify those who are likely to benefit from referral for therapy.

To evaluate the efficacy of an energy and sleep enhancement (EASE) intervention to relieve fatigue and sleep disturbance and improve health-related functional status.    

One hundred fifty-three individuals receiving chemotherapy were randomized to the EASE intervention and 139 were randomized to an attention control intervention. Participants in each group received three telephone sessions taught by a specially trained oncology nurse and a separate written handbook for each assigned intervention. The EASE intervention was based on the common sense model and involved appraisal and representation of symptoms, with a focus on fatigue and sleep disturbance, including communication of individualized strategies for fatigue management and sleep enhancement. The control intervention focused on information about nutrition and a healthy diet. The primary outcomes of fatigue, sleep disturbance, and functional status were measured before chemotherapy, day 4 after first treatment (baseline), and 43 to 46 or 57 to 60 days later (follow-up), depending on the chemotherapy cycle length. Two secondary outcomes, pain and depression, were chosen for evaluation, but not targeted for the intervention, because of an increasing body of evidence linking them to fatigue.

• Two hundred seventy-six patients (83% female and 17% male) receiving chemotherapy were included.
• Mean age was 53.9 years (SD = 12.02).
• The most common cancer diagnoses were breast (55%), lung (17%), lymphoma (8%), and ovarian (6%).
• Of the patients, 90% were Caucasian, 70% were married, 42% were college educated, and 95% were treated with chemotherapy alone.

• Multi-site study conducted at two universities:  one community cancer center and one comprehensive cancer center
• Outpatient
• The intervention was delivered by nurses at Fox Chase Cancer Center, Philadephia, PA
   

Patients were undergoing the active treatment phase of care.

This was a randomized, controlled trial using repeated measures and an attention control.

• Demographic and clinical information form    
• General Fatigue Scale (GFS)
• Profile of Mood States Fatigue subscale (POMS-F)
• Pittsburgh Sleep Quality Index (PSQI)
• Octagonal Basic Motionlogger Actigraph
• Morin Sleep Diary
• Brief Pain Inventory (BPI)
• POMS Depressive symptoms subscale (POMS-D)
• Symptom Checklist (SCL)
• Adapted BPI interference items (SXINT)
• Short Form 12 Health Survey (SF-12)
• Eastern Cooperative Oncology Group (ECOG) Performance Status
   

Fatigue and patient-reported sleep disturbance were moderately elevated in both groups at baseline and follow-up. Actigraphy revealed that the total sleep time was almost eight hours, and sleep efficacy was in the normal range of greater than 85% for both groups at both time points. Physical functioning was diminished and at the same level as a sample with serious illness. Mental functioning was in the normal range. The EASE intervention did not improve fatigue, reduce sleep disturbance, or prevent functional decline during chemotherapy. Both the EASE intervention group and the control group had an increase in fatigue and decline in physical functioning over time. ANOVA revealed no statistically significant group-by-time effects for fatigue, sleep disturbance, or functional status. A positive outcome in both groups was a decrease in the average number of nighttime awakenings over time. Unemployed individuals showed greater benefit from the EASE intervention and reported less pain and symptom interference.

In patients with cancer undergoing chemotherapy, the EASE intervention did not significantly improve fatigue, sleep disturbance, or physical functioning compared to the control group. Potential explanations include high variability or floor effect for fatigue, incorrect timing of measures, insufficient amount or dose of the intervention, and confounding effects of gender. Future research should consider screening for symptom severity and tailoring interventions.

• The ineffectiveness of EASE could be affected by the intervention dose, timing of the measures, and the large number of participants with low symptom severity.
• There was an overrepresentation of patients with breast cancer and underrepresentation of patients with lung cancer.
• Factors that may have affected the outcome included variation in populations, treatments being received, and lack of control over the severity of symptoms.

Future research directions were clearly described in the study, and practice implications included:  many individuals with multiple symptoms during chemotherapy could benefit from effective behavioral interventions conducted over time by skilled nurses. Further research could inform nurses of the most effective management methods to control symptoms.

The energy conservation and activity management (ECAM) intervention consisted of information provision, guidance in formulating and implementing a plan for energy conservation and activity management, and support in appraising the effectiveness of symptom management efforts. The intervention included completing a journal to monitor fatigue, sleep, rest, activity, and other symptoms; listing and prioritizing usual activities; and creating a tailored energy conservation plan. The intervention was delivered by nurse counselors in three telephone sessions that were 15 to 30 minutes in length.

• The study included 396 adults (age range 18–83 years); 85% were women, and most were Caucasian.
• Multiple diagnoses were included, but 71% of participants had breast cancer.
• All participants were initiating treatment with chemotherapy (47%), radiotherapy (44%), or concurrent chemoradiotherapy (9%).

Outpatient services of two large university cancer centers

Patients were undergoing the active treatment phase of care.

The study was a randomized, clinical trial with a repeated-measures design and an attentional control group.

• Profile of Mood States (POMS)
• Schwartz Cancer Fatigue Scale (SCFS)
• General Fatigue Scale (GFS)

• The ECAM intervention had a statistically significant effect in reducing fatigue, but the clinical effect was modest.
• The intervention group experienced significantly less disruption of usual activities compared with the control group, although the intervention was not associated with changes in overall functional status.

Efficacy findings were not confounded by the inability of patients who were in poorer health to complete the data collection process.

• Overrepresentation of women and a breast cancer diagnosis limits the generalizability to men, patients with other diagnoses, and those in poorer health.
• The amount of missing data was substantial. 
• Costs were not addressed.

Minimal training with the intervention materials is needed.

The energy conservation and activity management (ECAM) intervention included completing a journal to monitor fatigue, sleep, rest, activity, and other symptoms; listing and prioritizing usual activities; and creating a tailored energy conservation plan. The intervention was delivered by nurse counselors in three telephone sessions of 15 to 30 minutes in length.

• The study sample included 38 adults in two groups:  radiotherapy (n = 18; mean age = 59.4 years; 70% female; 84% Caucasian) and chemotherapy (n = 20; mean age = 57.4 years; 91% female; 95% Caucasian).
• The control group included 182 adults (mean age = 55.1 years; 58% female; 95% Caucasian).

• Experimental participants were outpatients in a National Cancer Institute–designated cancer center.
• Patients in the control group were from a multi-site study on fatigue measurement.

Patients were undergoing the active treatment phase of care.

• The study used a single group pre-/posttest design.
• A nonequivalent control group from another study was used for posttest comparisons.

Profile of Mood States (POMS) Fatigue scale

• The intervention was well tolerated and acceptable to patients.
• Results showed a trend for the two groups to differ at both points in time, with the control group exhibiting higher fatigue scores than the ECAM group.

• The study had a small sample size.
• The control group was a nonequivalent.
• The population was vulnerable, with many medical problems that can effect adherence.

Minimal training with the intervention materials is needed.

Databases: CINAHL, MEDLINE, PsycLIT, and CANCERLIT

The study evaluated 36 randomized clinical trials (RCTs), seven quasi-experimental trials, five  descriptions, six reviews, and one practice guideline published 1980–2000.

In 22 of 36 RCTS, psychoeducational interventions benefited patients with symptoms of depression.

The evidence dervied from this review supports the benefit of psychoeducational interventions for depression in patients with cancer.

STUDY PURPOSE: To evaluate the effectiveness of opioids in relieving the symptom of dyspnea in people with advanced disease

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 26 in review, 18 in meta-analysis 
• TOTAL PATIENTS INCLUDED IN REVIEW = 276 in meta-analysis
• SAMPLE RANGE ACROSS STUDIES: 6–25
• KEY SAMPLE CHARACTERISTICS: Cancer, chronic obstructive pulmonary disease (COPD), and heart disease were included.

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

Based on change in dyspnea from baseline, no statistically significant difference existed with opioids across seven studies. This evidence showed high heterogeneity and low overall quality. A comparison of post-treatment dyspnea scores in 11 studies showed significant benefit with opioids (standard mean difference [SMD] = –0.28, 95% confidence interval [CI] [–0.5, –0.05], p = 0.02). No significant effects (two studies) existed for nebulized opioids. Six studies were of patients with cancer. A few studies evaluated breathlessness in terms of exercise tolerance only.

The findings show that oral opioids have some benefit for the relief of dyspnea and may have some benefit for short-term improvement in exercise capacity.

• Mostly low quality/high risk of bias studies
• High heterogeneity
• Low sample sizes
• No subgroup quantitative analysis; differences for various patient subgroups were not analyzed.

Oral opioids are of benefit for reducing dyspnea. Nebulized opioids were not shown to be effective.