To determine the effects of a behavioral therapy (BT) sleep intervention (individualized sleep promotion plan [ISPP]) on cancer-related fatigue over a one-year period in women receiving adjuvant chemotherapy for breast cancer.

Patients at each study site were stratified according to number of planned anthracycline-based treatments and good versus poor sleep quality. Patients were then randomly assigned to the ISPP group or a control group that received care regarding health eating (HEC), which received the same amount of individual time and attention as the ISPP group. At baseline, patients in the ISPP group spent 90 minutes with the research nurse to develop a 12-item ISPP plan. Two days before all treatments, they spent another 30 minutes with the research nurse revising the plan based on sleep diaries and plan adherence data. After each revision, plans were reinforced in a 15-minute, in-person session seven to nine days after the revision. Plans included

• Stimulus control
• Modified sleep restriction
• Relaxation therapy
• Sleep hygiene counseling.

Thirty-minute sessions were held to revise the BT plan again at 30, 60, and 90 days after the last chemotherapy treatment. HEC participants received in-person sessions of equal time and attention before each treatment and at 30, 60, and 90 days after the completion of chemotherapy.

• In total, 217 patients (100% female) completed the study and were analyzed.
• Mean age was 52.14 years (range 29–83).
• All patients had breast cancer.
• All patients were receiving adjuvant chemotherapy.
• In each group, 14% of the patients had a cancer stage above II, at IIIA.
• Of the patients, 75% had at least some college education.
• The majority of patients were employed outside the home.
• Patients were excluded if they had a self-reported comorbidity associated with poor sleep and fatigue.

• Multi-site
• Twelve oncology clinics

This was a randomized, controlled trial with a one-year follow-up.

• Symptom Experience Scale (SES) to measure distress experiences of nausea, pain, appetite, bowel pattern, concentration, and appearance
• Hospital Anxiety and Depression Scale (HADS)
• Medical Outcomes Study Short Form 36 General Health Survey, version 2 (MOS-SF 36-v2)
• Piper Fatigue Scale:  22-item scale, Crohnbach’s alpha = 0.93-0.98
• Pittsburgh Sleep Quality Index (PSQI):  Crohnbach’s alpha = 0.74-0.83
• Daily sleep diary
• Wrist actigraph to quantify continuous monitoring of body movement for total sleep time after onset and sleep efficiency:  percent of time asleep after falling asleep out of total time in bed, number of awakenings, and time and percent of time awake after sleep onset

The BT group had a significant improvement in sleep quality compared to the HEC group at 90 days (p = 0.002) but not at one year (p = 0.052). Higher fatigue (p = 0.027) and higher anxiety (p = 0.012) at baseline were associated with poorer sleep at one year. There were no differences in most diary and objective sleep findings at selected times over the year. Sleep diary and actigraph findings did not coincide for either group. Values recorded in the diaries tended to show better sleep time and percent and lower numbers of awakenings than the actigraph findings. Moderate to severe fatigue was reported at one year by 20% of patients in the BT group and 24% in the HEC group. Fatigue changed over time for both groups, but there were no significant differences between the groups. PSQI scores over time were significantly better in the BT group (p = 0.013).

The BT intervention improved global sleep quality but did not improve fatigue in women over a period of one year. Baseline anxiety was associated with higher fatigue and poor sleep at one year.

• Participants had relatively mild sleep disruptions at baseline, which may have limited the effect and effect size of the sleep and fatigue scores.
• Differences in patient perception by diary and actigraph findings were not explained.
• The coscientist model used in the BT group incorporated participant freedom to design their own BT plan. A drawback of this approach was that patients often chose strategies with easier habits to alter than those that might be most effective.
• There was limited diversity in the sample demographics in terms of ethnicity and education level.

To determine the effect of behavioral therapy (BT)—specifically, an individualized sleep promotion plan (ISPP)—on sleep quality and fatigue in patients with breast cancer undergoing adjuvant chemotherapy.

Eligible women who consented to participate were randomized using stratified random sampling to either the BT group or to a healthy eating control (HEC) group prior to adjuvant chemotherapy. Patients completed questionnaires at baseline and wore a wrist actigraph for two days prior to initial treatment. Patients randomized to the BT group developed an ISPP during individual visits with the research nurse two days prior to treatment. Modifications to this plan were made two days prior to each treatment and 30 days after the last treatment. Modifications were based on patients' sleep diary data and treatment adherence. BT plans were reinforced during 15-minute sessions seven days after each revision. Patients in the HEC group received equal time and attention during individual visits and received information on healthy eating topics at each visit. Patients in the HEC group were referred to their treatment clinic for questions about fatigue and sleep.

• The study was comprised of 219 female patients with breast cancer.
• Mean age was 52.13 years (range 29–79) in the BT group and 52.16 years (range 30–83) in the HEC group.
• Patients had an initial diagnosis of stage I to IIIA breast cancer and had undergone either modified radical mastectomy or lumpectomy.
• Of the patients, 70% were partnered and 74% had at least some college education.
   

The study was conducted in 12 oncology clinics in the Midwestern United States.
 

Patients were undergoing the active treatment phase of care.

This was a randomized, controlled trial.

• Symptom Experience Scale (SES):  This scale measures frequency, intensity, and distress associated with six symptoms associated with cancer treatment. Scores for fatigue and sleep were not included in the mean SES score because they were measured in-depth by other study instruments.    
• Hospital Anxiety and Depression Scale (HADS): This scale measures anxiety and depression symptoms.
• Medical Outcomes Study Short-form General Health Survey (MOS-SF 36-v2):  The physical functioning subscale of this measure was used to measure physical functioning prior to cancer diagnosis.
• Piper Fatigue Scale (PFS):  The PFS is a 22-item scale of subjective cancer-related fatigue. The PFS was used at each treatment because fatigue was expected to fluctuate from treatment to treatment. Higher scores on the PFS indicate worse fatigue. Reported internal consistency for this study was 0.93 to 0.98.
• Pittsburgh Sleep Quality Index (PSQI):  The PSQI is a 19-item subjective measure of sleep quality over the past month. Seven component scores are summed to obtain global scores ranging from 0 to 21, with higher scores indicating greater sleep difficulties. In women with breast cancer, Cronbach’s alpha for global PSQI score is 0.80; it was 0.74 to 0.83 for this study.
• Wrist actigraphy and daily diaries were used to measure sleep variables. The study used the Motionlogger® Actigraph with one-minute epochs. Variables included total sleep time after sleep onset, sleep efficiency, number of awakenings, and minutes and percent awake after sleep onset. Actigraphs were recorded 48 hours before the initial treatment, for seven days and nights during treatment and for seven days and nights 30 days after the last treatment.
  
  
  
  
   

Mean PSQI scores in both groups were greater than five, which indicated poor sleep compared to the general population; however, mean scores were not greater than eight, a cutoff score associated with poor sleep quality in patients with breast cancer. Actigraphy and diary data showed normal sleep duration and sleep efficiency in both groups across treatment and follow-up. Number of awakenings after sleep onset measured by both sleep diaries and actigraphy were higher than normal in both groups. Significant differences between sleep diaries and actigraphy were observed for all sleep variables (p < 0.01 for all variables), with lower numbers of awakenings and higher sleep efficiency per diary data in the BT group. A significant group by time interaction was found for changes in the PSQI, with sleep quality improving in the BT group (p < 0.049). Although not significant, there were trends towards improved sleep quality over time in the BT group per actigraphy for total sleep time and number of awakening and per sleep diary for sleep efficiency. Perceived fatigue changed significantly over time in both groups (p < 0.001), with increased fatigue during treatments and decreased fatigue after the end of treatments in both groups. There was no apparent effect of BT on fatigue levels.

Patients in the BT group showed greater improvement in sleep quality over time than those in the the HEC group, although perceptions of improved sleep quality were not consistently associated with objective sleep measures, sleep diaries, or reported fatigue. BT was not shown to have an effect on fatigue.

• There was a lack of true baseline values of sleep and fatigue because patients were enrolled after surgery.
• There was no control of patients’ expectations of treatment.
• There were modifications to stimulus control and restriction therapy within the BT intervention model.
• The study population lacked racial/ethnic diversity.

BT may be used by trained nurses to improve sleep quality in patients with breast cancer receiving adjuvant chemotherapy. Further research is needed to determine the long-term effects of BT on sleep quality and fatigue in this population.

To evaluate the outcomes of an intervention designed to promote sleep and modify fatigue after adjuvant breast cancer chemotherapy.

A multicomponent cognitive-behavioral therapy in the form of a four-part intervention consisting of sleep hygiene counseling, relaxation therapy, sleep restriction, and an individualized sleep promotion plan (ISPP) stimulus control was used. It started two days before the first chemotherapy treatment; continued during treatment; was revised 30, 60, and 90 days after the last treatment; and was reinforced seven days later. Sleep and fatigue were the outcomes measured.

• The study was comprised of 21 female Caucasian patients with stage I or II breast cancer following adjuvant chemotherapy.
• Mean patient age was 55.3 years (range 43–66).

The study was conducted in the Midwestern United States in the patients’ homes.

Patients were undergoing the long-term follow-up phase of care.

This was a prospective, repeated measures, quasiexperimental feasibility study.

• Pittsburgh Sleep Quality Index (PSQI)
• Daily diary
• Wrist actigraph

High adherence to the four components of the ISPP was found, except for stimulus control. Sleep latency remained stable. Sleep efficiency ranged from 82% to 92%, and total rest ranged from seven to eight hours per night. The number of night awakenings ranged from 10 to 11 per night.

• The pilot study was not designed to test the effectiveness of the intervention.
• Research RN training was required.
• Actigraphs incurred a cost.

A multicomponent cognitive-behavioral therapy in the form of a four-part intervention consisting of sleep hygiene counseling, relaxation therapy, sleep restriction, and an individualized sleep promotion plan (ISPP) stimulus control was used. It began two days before the first chemotherapy treatment, was revised before each treatment, and was reinforced seven days after each treatment. Restrictions were delivered by RNs. Sleep and fatigue were the outcomes measured.

• The study was comprised of 25 female Caucasian patients with stage I or II breast cancer during adjuvant chemotherapy.
• Mean patient age was 54.3 years (range 40–65).

The study was conducted in the Midwestern United States, in urban oncology clinics and the patients’ homes.

Patients were undergoing the active treatment phase of care.

This was a prospective, repeated measures, quasiexperimental, feasibility study.

• Pittsburgh Sleep Quality Index (PSQI)
• Daily diary
• Wrist actigraph

Sleep latency, sleep efficiency, total rest, and ratings of feeling refreshed on awakening were stable. Time awake after sleep onset and nighttime awakenings exceeded desired levels.

• The pilot study was not designed to test the effectiveness of the intervention.
• Research RN training was required.
• Actigraphs incurred a cost.

Patients received a multi-component, cognitive-behavioral therapy (CBT), individual sleep promotion plan (ISPP) that included

• Sleep hygiene
• Relaxation prescription
• Stimulus control
• Sleep restriction delivered by a registered nurse (RN).

The ISPP started two days before the first prescription; continued during chemotherapy prescription; was revised 30, 60, and 90 days after the last prescription; and was reinforced seven days later. There were three doses and reinforcements.

• Twenty-one Caucasian patients (100% female) were included. 
• Mean age was 55.3 years (range 43–66).
• Patients had stage I or II breast cancer following adjuvant chemotherapy.

• Midwestern United States
• Patient homes 

Patients were undergoing the long-term follow-up phase of care.

This was a prospective, repeated measures, feasibility study with a single group and no control.

• Piper Fatigue Scale (PFS) and single fatigue intensity item
• Piper’s Integrated Fatigue Model (IFM)
• Adherence
• Sleep

Adherence to the intervention was high except for stimulus control. Fatigue scores were not significantly different over time.

• The pilot study was not designed to test the effectiveness of the intervention.
• The study had a small sample size.
• Research RN training was needed.
• The actigraph had costs.

Patients received multicomponent cognitive-behavioral therapy (CBT). Individual sleep promotion plans (ISPPs) included

• Sleep hygiene 
• Relaxation prescription
• Stimulus control
• Sleep restriction delivered by a registered nurse (RN). 

Each plan started two days before the first prescription, was revised before each prescription, and was and reinforced seven days after each prescription. There were four doses and reinforcements.

• Twenty-five Caucasian patients (100% female) were included.
• Mean age was 54.3 years (range 40–65).
• Patients had stage I or II breast cancer and were receiving adjuvant chemotherapy.

• Midwestern United States
• Urban oncology clinics
• Patient homes

Patients were undergoing the active treatment phase of care.

This was a prospective, repeated measures, feasibility study with a single group and no control.

• Piper’s Integrated Fatigue Model (IFM)
• Piper Fatigue Scale (PFS) and single fatigue intensity item
• Adherence
• Sleep

• There was moderate to high adherence (46%–80%) to the components of the sleep plan.
• Fatigue on the PFS two days postchemotherapy was stable over time.
• Fatigue intensity was lower (not significant) postchemotherapy three but rebounded after chemotherapy four.

• The pilot study was not designed to test the effectiveness of the intervention.
• The study had a small sample size.
• Research RN training was needed.
• The actigraphs had costs.

To determine the effectiveness of a behavioral therapy (BT) intervention, an individualized sleep promotion plan (ISPP), on sleep quality and fatigue in women with breast cancer receiving adjuvant chemotherapy.

Participants were recruited and screened for eligibility between 2003 and 2006. Eligible women interested in participation were visited by a research nurse who completed the randomization procedure, administered baseline questionnaires, and had patients wear an actigraph two days prior to the initial treatment. The intervention was delivered by research nurses who were trained by a sleep psychologist.

Those assigned to the BT group developed a 120-item ISPP with the research nurse according to the nurse's review of responses to measures to identify areas of sleep difficulty. Advice and information was tailored to individual needs. Revisions to the ISPP were made in 30-minute appointments made with participants two days prior to each treatment and 30 days after the last treatment. Reinforcement of the plan was made in 15-minute appointments seven days after each revision. Each ISPP included

• Modified stimulus control
• Modified sleep restriction
• Relaxation therapy
• Sleep hygiene counseling.

Patients in the control group received equal time and attention at each home visit and were provided with general support and a discussion of a new healthy eating topic.

• In total, 217 patients (100% female) completed the study and were analyzed.
• Mean age was 52.14 years (range 29–83). 
• All patients had breast cancer.
• All patients were receiving adjuvant chemotherapy.
• In each study group, 14% of patients had cancer stage above II, at IIIA.
• Of the patients, 75% had at least some college education.
• The majority of the patients were employed outside the home.
• Patients were excluded if they had a self-reported comorbidity associated with poor sleep and fatigue.

Multisite

This was a randomized, controlled study.

• Symptom Experience Scale (SES) to measure the distress experiences of nausea, pain, appetite, bowel pattern, concentration, and appearance
• Hospital Anxiety and Depression Scale (HADS)
• Medical Outcomes Study Short Form General Health Survey, version 2 (MOS-SF-36-v2)
• Piper Fatigue Scale (PFS):  22-item scale, Crohnbach’s alpha = 0.93-0.98
• Pittsburgh Sleep Quality Index (PSQI):  Crohnbach’s alpha = 0.74-0.83
• Daily sleep diary
• Wrist actigraph to quantify continuous monitoring of body movement for total sleep time after onset and sleep efficiency:  percent of time asleep after falling asleep out of total time in bed, number of awakenings, and time and percent of time awake after sleep onset

Baseline sleep quality measures indicated mild fatigue, somewhat poor sleep quality, low levels of symptom distress, and normal anxiety and depression levels. PSQI scores indicated lower sleep quality than the general adult population but better scores than those previously associated with poor sleep quality in patients with breast cancer. There were significant differences over time on all sleep variables from the diaries and actigraphs (p < 0.01). Diaries showed a significantly lower number of awakenings (p = 0.032), a lower average amount of time awake while in bed (p = 0.027), and higher sleep efficiency (p = 0.001) in the BT group.  Fatigue scores in both groups increased during treatment and decreased after treatment ended (p < 0.0001). This pattern was similar in both study groups. Perceived fatigue was similar between the two groups. There was a trend of improved sleep quality over time (PSQI) in the BT group.

The four-component ISPP was associated with improved sleep quality over time, better sleep efficiency, and fewer awakenings. Findings suggested that perceptions of improved sleep quality were not consistently associated with diary entries or objective sleep measures.

• Study participants tended to have relatively good sleep quality and low fatigue prior to chemotherapy compared to other reported patients with breast cancer. This may have reduced the effects seen and makes the clinical impact of findings unclear.
• The study ended 30 days after the last treatment; therefore, the longer-term effectiveness cannot be determined.
• The intervention was provided by trained nurses rather than sleep specialists, which may have affected the findings.
• The relative effectiveness of nurse-delivered BT has not been examined.

To evaluate the efficacy and safety of megestrol acetate (MA) in palliating anorexia-cachexia syndrome in patients with cancer, AIDS, or other underlying pathologies

Studies that met the following eligibility criteria were reviewed.

• Double-blind, single-blind, or unblended randomized controlled trials (RCTs)
• RCTs that assessed the use of MA compared to a placebo or other drug treatments in patients diagnosed with anorexia-cachexia related to cancer, AIDS, or other underlying pathologies
• Crossover studies that reported the results of the first phase of the study

Data extraction was conducted by two independent authors. Methodological quality was assessed using the Oxford scale (Jadad, 1996). Scores for methodological quality were generally high. Studies in which more that 50% of patients were lost to follow-up were excluded from the analysis.

• Thirty trials, which included a total of 4,123 participants, met the eligibility criteria.
• Mean participant age was 58 years in the treatment groups and 57 years in the control groups.
• The proportion of males to females in the treatment groups was 1,140/502 and 1,733/731 in the control groups. 
• The doses of MA administered ranged from 100 mg to 1,600 mg per day.
• Twenty-one trials compared different doses of MA with a placebo; four compared different doses of MA with other drugs; three compared different doses of MA; and two compared MA with other drugs and a placebo.

Results for MA versus placebo: In patients with cancer, a statistically significant improvement in appetite was observed in the patients treated with MA. Weight gain also was observed in this group.

Results for MA versus other drugs: MA did not show benefits in terms of appetite improvement in comparison to other drugs. Significant differences in quality of life were not reported.

Results for different dose levels of MA: Using 400–800 mg as a cutoff and comparing high to low doses, significant differences in appetite outcomes could not be appreciated.

MA improves appetite and weight gain in patients with cancer. Due to study heterogeneity, no overall conclusion can be drawn about its impact on quality of life; a more systematic approach was suggested for the measurement of quality of life in the trials. The clinical effects of MA do not appear to be dose-related, and the mechanism by which MA increases weight gain is unknown. 

MA cannot be recommended for use in patients with AIDS or anorexia-cachexia related to other pathologies. Edema, included in the adverse event profile of MA, is the only significant difference between the treatment and a placebo.

To study effects of armodafinil on cancer-related fatigue in patients with multiple myeloma

Patients were randomly assigned to study groups in this crossover design study. One group was a treatment-only arm that got armodafinil, and the other was a placebo-first arm that received a placebo followed by armodafinil. Patients received armodafinil 150 mg once daily for 56 days in the treatment-only group. In the other group, patients received a placebo for 28 days and armodafinil on days 29–56. Assessments were done at baseline and at days 15, 28, 43, and 56. Five variations of study assessments were used to address potential memorization effects, and the order in which versions were used was varied.

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

• PHASE OF CARE: Active antitumor treatment

Double-blind, randomized, crossover-controlled trial

• Brief Fatigue Inventory (BFI)
• Hospital Anxiety and Depression Scale (HADS)
• Epworth sleepiness scale
• Trail Making Test (TMT) version B
• Symbol Digits Modalities Test (SDMT)
• Digit span test
• Functional Assessment of Chronic Illness Scale–Fatigue (FACIT-F)
• Functional Assessment of Cancer Therapy–General (FACIT-G)

Adverse effects observed during armodafinil treatment were similar between groups. Fatigue as measured by the BFI scale decreased significantly for both groups over time with no difference between groups. Outcomes measured by FACIT scores increased significantly in the placebo-first group by day 28, and FACIT fatigue scores improved significantly in both groups. Anxiety decreased significantly from baseline in both groups. Depression scores only declined significantly in the placebo-first group by day 28. Degree of sleepiness decreased significantly in the placebo group. There were no significant changes in study measures between day 28 and day 56 in which all patients received armodafinil.

Armodafinil was not shown to significantly improve symptoms of fatigue, anxiety, or depression in patients with multiple myeloma.

• Small sample (< 100)
• Other limitations/explanation: 20% drop-out rate prior to day 56; more patients in the treatment-only group dropped out.

Armodafinil, a medication similar to modafinil, was not shown to be effective for the reduction of fatigue, anxiety, or depression.

The type of evidence found was based on review of the literature and clinical expertise.

The panel focused mainly on colorectal cancer and patients receiving chemotherapy with FU and CPT-11 or radiation therapy, so this is not applicable to other populations (i.e., transplant population).

Diarrhea is a challenge for patients receiving chemotherapy and/or radiation therapy for their cancer. Through in-depth gastrointestinal assessments and optimal treatment, nurses are able to minimize the potential for increased toxicities associated with chemotherapy-induced diarrhea.