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.

DATABASES USED: MEDLINE (May 2002–May 2005), selected studies related to amifostine

KEYWORDS: stomatitis, mucous membrane, mucositis (text in titles and abstracts)

INCLUSION CRITERIA: Limited to \"neoplasm\" and English language

FINAL NUMBER STUDIES INCLUDED = 29 trials included, 6 covered in detail; pilot studies and randomized, controlled studies included

SAMPLE RANGE ACROSS STUDIES: Sample sizes range from small to more than 200

KEY SAMPLE CHARACTERISTICS: Patients with head and neck cancer receiving radiation alone; patients with cancers of various origin receiving combination chemoradiation or radiation alone; patients receiving intensity-modulated radiation therapy; and studies examining routes of administration in patients with head and neck cancer, patients with prostate cancer, and patients receiving epirubicin

The study did not provide sufficient evidence for recommendations related to amifostine and prevention or management of oral mucositis. The authors recommended maintaining the original guideline from the Multinational Association of Supportive Care in Cancer—chemoradiation for non-small cell lung cancer for prevention of esophagitis (level of evidence III, grade of recommendation C). Several small studies demonstrated prevention of proctitis in patients with only rectal carcinoma. No effect was shown for other pelvic cancers. Therefore, the authors suggested that the guideline be revised to include the recommendation of amifostine at least 340 mg/m² IV daily prior to radiation (level of evidence III, grade of recommendation B) for rectal carcinoma to prevent proctitis. For patients with hematologic disorders, no significant data could reinforce any recommendations. Possible future uses and routes of amifostine also were discussed.

To determine the feasibility of conducting a larger phase III trial to investigate the effectiveness of TENS for control of cancer-related bone pain

Patients were randomized to receive either active TENS at the first application and placebo TENS at the second application, or vice versa. Researchers responsible for outcome assessments were blinded to patient group. Placebo TENS was delivered using devices that were identical in appearance but delivered no current output. Patients were informed that sometimes they would feel a tingling sensation and sometimes they might not feel this. Patients were instructed not to tell the research observer any sensations they were feeling. Pain intensity measures were obtained at baseline, then repeated after 30 and 60 minutes of TENS application. Patients returned for the second TENS application two to seven days later and experienced an identical procedure. TENS application was given using a single channel device, and placement was based on recommendations for conventional TENS of the International Association for the Study of Pain. Pain was assessed at rest and on a patient-specified movement. Patients continued their current pain medication regimen.

• The study reported on a sample of 24 randomized patients, with 19 analyzed.
• Mean patient age was 72 years, with a range of 40–91 years. 
• The sample was 75% male (18) and 25% female (6). 
• The majority of patients had prostate cancer. Additional types included breast, lung, thyroid, and renal.
• All patients had radiologic evidence of bone metastases, pain rated as at least 3 on a 10-point rating scale, and an expected survival of longer than four weeks.
• Most (87%) were being treated with strong opioids, including morphine, fentanyl, or oxycodone, 79% had previous radiotherapy, and 33% had received biophosphonates.
• The most common sites of painful bone metastases were pelvis, lumbosacral spine, and lower limbs.
• The majority of patients had an Eastern Cooperative Oncology Group performance status of 1 or 2.
• Patients were on stable pain medication regimens.

• Multisite
• Outpatient setting in the United Kingdom

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

• Numerical pain rating scale (1–10)
• Verbal rating scale (four categories from no pain to severe pain)
• Short Form McGill Pain Questionnaire (SF-MPQ)
• Patient satisfaction questionnaire designed by authors regarding benefit, ease of use, and impact on pain or rest

The mean pain change in pain intensity score for active TENS was –0.84 compared with placebo TENS of –2.16. The mean change with movement was –2.32 for active TENS compared with placebo change of –2.0. at one hour. The mean pain relief on movement was higher with active TENS. The difference in proportion of patients who reported good or very good pain relief on movement with active TENS by verbal ratings was 36.8% (95% CI 7.5–66.2%). There were no clear patient preferences between active and placebo TENS. Three patients experienced adverse events, increased pain with TENS application, that were deemed likely to be or definitely related to TENS use.

TENS has the potential to provide improved pain relief on movement in patients with bone pain.

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

The purpose of this study was to determine feasibility and use findings to plan for a phase III study, rather than to determine intervention effect. Findings suggest that TENS may be more effective in pain relief on movement than for pain relief at rest for bone pain. Findings also showed an effect on the measure of pain relief, but not on the measure of pain intensity. This suggests that pain relief measurement may be more useful in clinical trials than just measurement of pain severity at given points in time.