To analyze the effects of a four-week yoga intervention on cancer-related fatigue and the burden of overall side effects in older cancer survivors

This report is a secondary analysis of a previously published multi-site, randomized, controlled trial to assess the effects of yoga on fatigue and sleep problems among patients with cancer who completed initial treatment. Participants aged 60 years or older who had completed fatigue measures were included in this analysis. Group yoga sessions were provided two days per week for four weeks. The program included breathing exercises, postures, and mindfulness exercises involving meditation, visualization, and affirmation. Random sessions were independently observed by study coordinators to verify the content.

• N = 97  
• MEAN AGE = 65.96 years
• MALES: 6%, FEMALES: 94%
• KEY DISEASE CHARACTERISTICS: Multiple tumor types; breast cancer most prevalent (65%)

• SITE: Multi-site    
• SETTING TYPE: Outpatient    
• LOCATION: New York

• PHASE OF CARE: Transition phase after active treatment
• APPLICATIONS: Elder care 

Single, blinded, randomized, controlled trial

• Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF)
• Clinical symptom inventory 11-point rating scale (Global symptom burden was calculated as the sum of all individual symptom scores ranging from 0–120.)

Participants attended an average of 6.2 of the eight yoga sessions. After the intervention, yoga participants reported a significantly lower level of fatigue compared to the standard care patients (p = 0.03) and a significantly lower global side effect burden (p < 0.01). Significant results were only in the physical and mental components of fatigue.

The findings of this study showed that yoga improved fatigue.

• Small sample (< 100)
• Risk of bias (no appropriate attentional control condition)  
• Risk of bias (sample characteristics)
• Key sample group differences that could influence results
• Other limitations/explanation: There was high variability among the sample in the time since initial treatment ended, this ranged from 2–24 months. The sample included very few men, and the majority of participants were white and well-educated. The duration of follow-up was only four weeks. Participants were aware of the study outcomes of interest, so there was an associated potential threat to the internal validity of the study

The findings of this study suggest that yoga may be beneficial to older cancer survivors for the reduction and management of cancer-related fatigue. Studies of yoga have tended to be done in women and individuals with relatively high formal education. Additional research is needed to examine the effectiveness and acceptance of this type of intervention in more diverse patient groups.

GM-CSF topically (Leukomax mouthwash)
Given in 250 ml 400 mcg recombinant Escherichia coli GMCSF once daily as soon as erythema was diagnosed, ordered to swish and swallow over period of 1 hr.
Control arm – conventional mouthwash (Hydrocortisone, Pantocain)
Patients also told to maintain strict oral hygiene using a soft toothbrush and fluoride toothpaste, and to avoid tobacco, alcoholic beverages, very hot and cold food, and spicy food.

Stratified for RT chem. Combination or RT alone.
All patients had daily rinses at least 3x/day. GM-CSF versus pantocain, hydrocortisone, cional kreussler, and bepathen (European product).

 

The study was comprised of 59 patients, recruited, 14 not randomized, patients = 45.
GMCSF group = 23,  21 control
18 and 17 completed trial

Jan 1997 – Oct 1998

Prospective, randomized, parallel grouped phase II clinical trial (non-blinded)

WHO scale for mucositis
 

No statistically significant evidence was reached in the grade of oral mucositis or the patient’s perception of oral pain.

Unable to determine therapeutic benefit of control arm product versus lack of effect of GM-CSF versus benefit of strict oral hygiene.

Authors conclude the agent cannot be recommended.
 

Intervention not effective
 

• Sample size small
• Selection of control arm agent
• \"Tremendous cost\" of agent

IV palifermin (recombinant human keratinocyte growth factor) 60 mg/kg was given for three consecutive days immediately before a conditioning regimen (total body irradiation [TBI] plus high-dose [HD] chemo). Additional doses administered on days 0, 1, and 2.

• The study reported on 212 patients with a median age of 48.5 years and an age range of 18–69 years.
• Patients were stratified according to the center and type of cancer; 106 were given palifermin and 106 received placebo.
• All patients had hematologic cancers and were receiving autologous stem cell transplant (SCT).

The study was conducted in a multisite setting.

This was a placebo-controlled, double-blind, phase 3, randomized trial.

• The World Health Organization (WHO) oral toxicity scale was used.
• The Radiation Therapy Oncology Group (RTOG) acute radiation-morbidity scoring criteria for mucous membranes was used.
• The Western Consortium for Cancer Nursing Research (WCCNR) revised staging system for oral mucositis was used.
• Use of analgesia and total parenteral nutrition (TPN) was recorded.
• Duration of mucositis was recorded.
• Incidence of mucositis was recorded.
• Mucositis was evaluated for 28 days.

• Fewer patients in the palifermin group had WHO grades 3 or 4 (63%) than in the control group (98%) (p < 0.001).
• Fewer patients in the palifermin group had WHO grades 4 (20%) than in the control group (62%) (p < 0.001).
• Patients in the palifermin group had a lower median duration of mucositis at 6 days versus 9 days in the control group (p < 0.001).
• Fewer patient in the palifermin group reported soreness of mouth and throat (29%) than in the control group (46.8%) (p < 0.001).
• Patients in the palifermin group reported lower use of opioids (212 mg morphine equivalents) compared to the control group (535 mg morphine equivalents) (p < 0.001).
• Incidence of TPN was lower in the palifermin group (31%) than the control group (55%) (p < 0.001).
• Adverse events were rash, pruritus, erythema, mouth and tongue disorders, and taste alteration.

Patients in the palifermin group experienced statistically significant decreases in incidence and duration of mucositis.

• One or more of the study researchers had a relationship with AMGEN, which manufactures palifermin.
• The study only looked at a hemotologic autologous SCT population.
• The trial only studied the IV formulation.
• Palifermin costs may be a limitation.

Patients in the study group received 910 mg/m² IV amifostine 15–30 minutes prior to  200 mg/m² melphalan prior to autotransplant for multiple myeloma (MM). 

• The study reported on a sample of 90 patients; 43 patients received amifostine, and 47 did not.
• The age range was 31–69 years with a median age of 54 years.

This was a multicenter study conducted between May 1999 and November 2000.

This was an open label, randomized study.

The World Health Organization (WHO) scale for mucositis, median duration of mucositis, duration of total parenteral nutrition (TPN), and duration of narcotics use were recorded.

• Patients in the amifostine group experienced a reduction in median grade of maximal mucositis and incidence of grades 2–4 mucositis compared to the control group. 
• Patients in the amifostine group were more likely to experience no mucositis than patients in the control group, although the difference was not significant.
• Median duration of maximal severity was 3 days in the control group and 4 days in the amifostine group (p = 0.18).
• The control group was more likely to experience severe delayed emesis compared to the amifostine group, although this difference was not significant. 
• No significant differences were found in the requirement for or duration of TPN or narcotics.

This study provided weak statistical evidence for the use of amifostine.

• This study was supported by Schering Plough, which also manufactured amifostine, and Amgen.
• Amifostine infusion toxicities were common in this study.

• FINAL NUMBER STUDIES INCLUDED = 102 (However, data from 82 studies were abstracted, WMES were calculated from 66 high quality studies, and a systematic level of evidence criteria was applied to evaluate 60 outcomes.)
• TOTAL PATIENTS INCLUDED IN REVIEW = 41 (control), 42 (intervention)
• SAMPLE RANGE ACROSS STUDIES: 4–322 patients
• KEY SAMPLE CHARACTERISTICS: 40% during treatment, 60% after treatment, 83% breast cancer, 90% randomized controlled trials, 80% aerobic (either alone or combined with another modality), 76% did not adequately describe their sample, and 57% described the intervention

PHASE OF CARE: Multiple phases of care

The majority of studies demonstrated a positive effect on upper and lower body strength and self-esteem with physical activity during treatment. The majority of studies also demonstrated a positive effect on aerobic fitness, lower body flexibility, lean body mass, quality of life, trial outcome index, breast cancer subscale, vigor and vitality, fatigue, immune parameters, pain, symptoms, and side effects post-treatment. Twenty-nine of 36 studies reporting on aerobic exercises reported no side effects from physical activity. Significant WMES were found post-treatment for fatigue (-0.54, p = 0.003).

In general, physical activity is well-tolerated during and after cancer treatment. More studies are needed on specific kinds of exercise and the structure of delivery. Physical activity studies with fatigue as an outcome have increased from five to 14 since 2005 for post-treatment interventions with 93% of studies showing positive results and 50% of them being statistically significant.

• Most of the studies involved patients with breast cancer.
• Considerations for the difficulty of making recommendations based on variations in dose response, cancer diagnosis, and stage of treatment during the intervention were acknowledged.

Patients can be educated that physical activity after a cancer diagnosis can be safe with modifications as necessary.

The mindfulness based stress reduction (MBSR) intervention was based on the main principle that purposeful management of awareness can be used repeatedly in the ongoing process of adapting to illness once experiential knowledge of key processes in the stress-response cycle is mastered. Objectives of program were to

1. Provide an opportunity to develop an understanding of one’s personal responses to stress and a means to modify them
2. Allow group member to take an active role in their healing process
3. Teach options for self-care that promote feelings of competence and mastery
4. Enhance feelings of well-being
5. Provide a safe and supportive group environment.

The intervention consisted of seven 90-minute weekly sessions. Patient outcomes were evaluated at baseline and at week 7 (end of intervention).

• N = 90 
• MEAN AGE = 51 years
• KEY DISEASE CHARACTERISTICS: Patients with cancer with multiple diagnoses and stages, with breast cancer being the most common (38%)
• OTHER KEY SAMPLE CHARACTERISTICS: Well educated with a mean of 15 years of formal education, convenience sample

• Randomized wait-list control design
  • MBSR (N = 53)
  • Wait-list control (N = 37)

• Profile of Mood States (POMS)

The MBSR intervention did not have a significant effect on improving fatigue outcomes for patients. When comparing pre- and post-test intervention scores, both the control and intervention groups experienced a decline in fatigue scores from baseline to week 7; however, this difference did not reach significance for either group.

In the initial sample of 109 patients enrolled in the study, 19 dropped out. A dropout analysis was performed, and initial POMS scores of dropouts were found to have significantly more mood disturbance on the subscales of anxiety, depression, fatigue, and total mood disturbance (p < 0.05).

• Because MBSR was a multi-component intervention, it is difficult to isolate the mechanisms of action or specific techniques they contributed to the improvements observed.
• It is possible that those assigned to the waitlist control group felt disappointment and may not have improved as much spontaneously over time as they would have otherwise.
• Because the dropout group demonstrated higher mood disturbance, the MBSR program may not be sufficient to treat patients with more serious disturbances.

To establish the safety and efficacy of modafinil for the treatment of fatigue in patients with non-small cell lung cancer

Patients were randomized to take either oral modafinil 100 mg or a matched placebo capsule. Patients took the medication on a fixed-dose titration schedule of one capsule daily for 14 days and then two capsules daily for the next 14 days. Assessments were done at baseline and on days 14 and 28.

• N = 160
• MEAN AGE = 68.9 years
• MALES: 50%, FEMALES: 50%
• KEY DISEASE CHARACTERISTICS: All patients had non-small cell lung cancer.

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

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

• Functional Assessment of Chronic Illness Treatment–Fatigue (FACIT-F) scale for fatigue
• Epworth Sleepiness Scale (ESS)
• Hospital Anxiety and Depression Scale (HADS)

Fatigue declined in all patients with no significant differences between groups. Modafinil appeared to be well-tolerated with no difference between groups in adverse events; however, more patients in the modafinil group withdrew from the study (p = .02). 42% of those receiving modafinil and 23% of those on the placebo reported that the treatment was not helpful.

Modafinil was not shown to be effective in reducing fatigue in this study.

• Subject withdrawals ≥ 10% 
• Other limitations/explanation: It is not clear what phase of care patients were in and whether receiving active treatment.  

The findings of this study do not show the efficacy of modafinil in the treatment of cancer-related fatigue. Nurses should be aware that there is insufficient evidence to support effectiveness of modafinil for fatigue and should advocate for the use of interventions that have demonstrated effectiveness.

To determine the feasibility of conducting a randomized, controlled trial to assess the efficacy and safety of modafinil for the treatment of fatigue in patients with lung cancer.

Patients with non-small cell lung cancer (NSCLC) took modafinil in a fixed dose-titration schedule (100 mg daily on day 1 and increasing in the second week to 200 mg daily) for 14 days.

• Twenty patients (6 females, 14 males) were included.
• Median age was 74 years. 
• All patients had NSCLC.

• Multisite
• Inpatient
• United Kingdom

This was an intervention feasibility study.

• Chalder Fatigue Questionnaire (CFQ)
• Epworth Sleepiness Scale (ESS)
• Hospital Anxiety and Depression Scale (HADS)
• Functional Assessment of Cancer Therapy-Fatigue (FACT-F)

• There was a change in fatigue between days 0 and 14.
• Mean fatigue decreased from 6.9 to 3.7.
• There were statistically and clinically significant improvements in fatigue scores from days 0 to 7.
• There was no statistically significant change from days 7 to 14.

It is feasible to conduct randomized, controlled trials.

The study had a small sample size, with less than 30 patients.

• This was an inexpensive pharmacologic intervention for cancer-related fatigue.
• Randomized, controlled trials are needed to confirm the benefit.
• The intervention was well tolerated in patients with advanced cancer.
• Poststudy, 10 patients chose to continue taking modafinil.

To evaluate a multimodal mind-body program (MMMT) compared to walking effect on fatigue in women with stage I–IIIA breast cancer

Participants in the intervention group underwent six hours of training in meditation, whole-food cooking, naturopathic strategies, and mindfulness by a multidisciplinary team. A sports therapist supervised a walking program in weeks 1, 3, and 10. Participants were encouraged to walk at home three times per week for 30 minutes. Participants in the control group also underwent a sports therapist-supervised walking program in weeks 1, 3, and 10. They also were encouraged to walk at home three times per week for 30 minutes.

• N = 55   
• AGE: Control mean: 55.3 years; MMMT mean: 58.1 years
• MALES: 0%, FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Average time first diagnosis: 39.7 months control, 61.9 months MMMT; stage I disease: 48% control, 30% MMMT; stage II disease: 44% control, 56.7% MMMT; stage IIIA disease: 0% control, 6.7% MMMT
• OTHER KEY SAMPLE CHARACTERISTICS: 20% smokers in MMMT group, 0 in control; mean fatigue in last month: MMMT 6.5, control 6.7

• SITE: Single site 
• SETTING TYPE: Outpatient 
• LOCATION: University of Duisburg-Essen, Germany

• PHASE OF CARE: Late effects and survivorship

• RCT

• German Fatigue Assessment Questionnaire with visual analog scale
• European Organization for Research and Treatment of Cancer EORTC QLQ-30
• Multidimensional Fatigue Inventory (MFI)
• Hospital Anxiety and Depression Scale (HADS)
• Menopausal Rating Scale

Unusual fatigue in the last week and last month was improved in both groups with no group differences. Anxiety in the MMMT group was improved compared to the control group (p = .043) during treatment but was not maintained in follow-up (p = .422). Both groups showed overall anxiety improvement. Reported pain between groups was improved in MMMT at follow-up compared to control (p = .031).  Menopausal symptoms decreased in both groups. No significant side effects were seen.

A home-based exercise program showed improvement in reported fatigue. The addition of a mind-body component showed no additional benefit.

• Small sample (< 100)
• Risk of bias (no control group)
• Unintended interventions or applicable interventions not described that would influence results
• Key sample group differences that could influence results
• Questionable protocol fidelity
• Subject withdrawals ≥ 10%

Home-based exercise is a reasonable and safe option for patients experiencing cancer-related fatigue.

To compare regimens using fosaprepitant and olanzapine for chemotherapy-induced nausea and vomiting (CINV) prevention

Patients on regimens for the prevention of CINV who were receiving highly emetogenic chemotherapy (HEC) received either a medication regimen of fosaprepitant, ondansetron, and dexamethasone, or a regimen of olanzapine, ondansetron, and dexamethasone. Those on the olanzapine regimen only received dexamethasone on day 1. Both groups had additional rescue medication as needed. All patients were assessed within 24–72 hours for CINV via follow-up phone calls, with results documented in the electronic medical record.

• N = 148
• MEAN AGE = 58.47 years
• AGE RANGE = 21–81 years
• MALES: 53%, FEMALES: 47%
• CURRENT TREATMENT: Chemotherapy, combination radiation and chemotherapy
• KEY DISEASE CHARACTERISTICS: All were receiving HEC. Tumor types were not reported.
• OTHER KEY SAMPLE CHARACTERISTICS: Of the patients, 38.5% were also receiving radiation therapy.

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

• PHASE OF CARE: Active antitumor treatment

• Retrospective cohort noninferiority design

Complete response defined as no emesis after cycle 1. A difference of 15% complete response (CR) rate was used as the limit for noninferiority testing.

The difference in the CR rate between groups was 8.9% in the acute phase, 12.9% in the delayed phase, and 8.6% overall. Statistical analysis showed that results in the olanzapine group were not inferior based on the difference level specified. Comparison of wholesale acquisition costs showed that the olanzapine regimen was less than 4% of the cost of the regimen using fosaprepitant ($8.58 versus $265.59).

The olanzapine regimen tested here was associated with less than a 15% difference in CR rate compared to a regimen containing fosaprepitant.

• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Measurement validity/reliability questionable
• How CINV was assessed and documented is not described.
• No subgroup analysis for those receiving concomitant radiation therapy
• No information is provided regarding the use of breakthrough medication and any associated costs.
• No information regarding nausea severity

This study showed that a regimen based on olanzapine was not inferior to one with fosaprepitant among patients receiving HEC if a less than 15% difference in CR rate is clinically acceptable. Individuals on the olanzapine had a higher prevalence of delayed phase CINV, though those in the olanzapine regimen also did not receive dexamethasone after day 1. The fosaprepitant regimen was much more expensive than the olanzapine regimen, so it may be a good alternative for patients with limited coverage or financial resources. Additional studies are needed to identify the most cost-effective regimens for CINV prevention, and this work needs to also provide greater focus on the prevention of nausea.