To determine whether cognitive behavioral therapy (CBT) for post-cancer fatigue has an effect on patients’ perceived cognitive functioning and/or neuropsychological test performance

Subjects were randomly assigned to intervention (CBT) or wait-list control (WLC) group. Participants were evaluated on six perpetuating factors of fatigue: inadequate coping with the cancer experience, fear of recurrence, dysfunctional beliefs concerning fatigue, sleep dysregulation, activity dysregulation, and low social support and negative social interactions. Results were used to customize the standardized modules for an individualized CBT intervention. Each hour-long CBT session was delivered by one of three trained therapists over a six-month interval. The number of sessions varied per participant since it was dependent upon when therapeutic goals were met. Participants were offered up to two booster sessions over an additional six months. Measurements were performed at baseline (T1) and at six months (T2).

• N = 98 (50 CBT and 48 WLC)    
• MEAN AGE = 44.9 years
• MALES: 51%, FEMALES: 49%
• KEY DISEASE CHARACTERISTICS: Primarily solid tumors (predominately breast and testicular cancer) as well some hematologic cancers
• OTHER KEY SAMPLE CHARACTERISTICS: Patients were included in the study if they were severely fatigued as defined by a score of ≥ 35 on the fatigue severity subscale of the Checklist Individual Strength scale and without evidence of a somatic origin. Additional eligibility criteria were completed last cancer treatment at least one year prior to study enrollment, had no evidence of cancer recurrence, and were not currently receiving psychological or psychiatric treatment.

• SITE:  Not stated/unknown   
• SETTING TYPE: Outpatient   
• LOCATION: Netherlands

PHASE OF CARE: Late effects and survivorship

Randomized clinical trial with waitlist control group

• Checklist Individual Strength (Concentration subscale)
• Sickness Impact Profile (Alertness Behavior subscale)
• Computerized simple-reaction time and choice-reaction time tasks
• Wechsler Adult Intelligence Scale (Symbol Digit Modalities Test)
• Checklist Individual Strength (Fatigue Severity subscale)

At baseline, most participants (78%) had clinically relevant difficulties with concentration as indicated by scores on the reaction time tasks; however, no differences existed between the intervention and control group. In contrast, the CBT group reported greater cognitive disability at baseline than WLC, as measured the CIS-concentration subscale (p = 0.04) and SIP-alertness subscale (p = 0.015). After intervention completion, there was a significant improvement in concentration and alertness behavior (p < 0.05) in participants who received CBT as compared to WLC. For CBT group, the improvements in self-reported concentration and alertness behavior were significantly associated with their decrease in fatigue severity (p < 0.001; p < 0.02); SDMT scores and computerized reaction time tests were slightly improved but not significant.

Individualized CBT may be an effective intervention in reducing self-reported fatigue. Although improvements in concentration and alertness behaviors were found, it is difficult to differentiate if they were related to reduced fatigue, CBT, or both. Improvements in perceived cognition were not associated with either depression or anxiety.

• Small sample (< 100)
• Risk of bias (no appropriate attentional control condition)
• Key sample group differences that could influence results
• Intervention expensive, impractical, or training needs
• Other limitations/explanation: 16% of subjects did not complete neuropsychological tests at T2; not statistically significant between groups; significantly higher number of WLC subjects received chemotherapy, which could possibly influence results; while CBT program was tailored for individual needs, the administration over a six-month interval by a trained therapist may limit general applications or feasibility in the clinical setting.

CBT decreased fatigue and improved perception of cognitive functioning over a six-month interval; however, the durability of those results are unknown. Further research is warranted to validate these findings and to determine whether this intervention can be adapted for general clinical use.

To evaluate the effects of active exercise using a facilitating apparatus with compression on arm lymphedema secondary to breast cancer

Patients received two sessions of four, 12-minute stints of exercise using an active apparatus pulley system. The device was a vertical iron wheel fixed to a 30-cm-high support on a metal bench. The patient revolved the wheel, thus elevating the shoulder and stretching the arm. A homemade short-stretch compression sleeve made of a cotton polyester material was used during one of the exercise sessions. Arm volume measurements were taken before and immediately after each exercise session.

• The study sample (N = 20) was comprised of female patients who had breast cancer.
• Mean age was 63.3 years, with a range 49–82 years.
• All patients had a mean difference in arm volumes of at least 200 ml.

The study took place at an outpatient setting in Brazil.

The study has clinical applicability for late effects and survivorship.

The study used an observational single group design.

Arm volume was measured by water displacement.

A mean reduction in arm volume of 24.6 ml was seen in the exercise session while wearing the compression garment (p < 0.0004). Without the compression garment, arm volume increased by a mean of 9.7 ml.

The apparatus used here was effective for provision of active exercise. Without the compression garment, exercise increased arm volume slightly. The low stretch, inelastic compression had a synergistic effect with exercise to reduce arm volume.

• The sample size was small, with fewer than 30 participants.
• The study had a risk of bias because of no control group or blinding. 
• The standard deviations reported showed high variability of results in the study sample, suggesting actual effects were highly variable even within this small sample. 
• Whether the mean is truly representative of overall group results was not clear.

Findings demonstrated the importance of use of a compression mechanism during exercise in patients with lymphedema.

To evaluate the efficacy of a new combination therapy for the management of lymphedema

All patients had a three-to-four hour weekly session that included manual lymph drainage, mechanical lymph drainage, and exercises using facilitating apparatuses and a compression sleeve made from a cotton-polyester material. Exercise and daily life activities were adapted for home use, and psychological and nutritional supports were provided. Compression sleeves were adapted for home use. Activities were individually evaluated and adapted for each patient by an occupational therapist to ensure they could be adapted to fit the treatment program. The textile used for low-stretch compression sleeves exert pressure with muscle activity and rest, and lengthwise elasticity allows flexibility in the limb.  Arm volume was measured monthly.

• The sample (N = 66) was comprised entirely of females. 
• Mean age of the sample was 58.8 years with a range of 33–72 years.

The study was conducted in a single-site, outpatient setting in Brazil.

 A prospective study design was used.

Water displacement was used to measure volume.

• Mean follow up was 12.3 months. 
• The mean volume difference at baseline was 559 ml. 
• An average of 70.1% volume reduction was found at the end of the study (p < 0.0001).

The model of treatment appeared to be effective in management of lymphedema among women with breast cancer.

• The study had a small sample size with fewer than 100 patients.
• Bias is a risk because of the lack of a control group, no blinding, and no random assignment. 
• No disease-related information or patient adherence information was provided.

This approach for lymphedema management appears to be effective. Methods shown here are similar to complete decongestive therapy, with differences in the textile used for compression sleeves, use of an apparatus for arm exercises, and once weekly manual lymph drainage.

The patient education intervention was delivered in three sessions and consisted of:  one-to-one education, training and counseling, and audio-visual computerized educational materials. In session one (first cycle of chemotherapy treatment), patients were introduced to the project and were given information about fatigue and how to manage it, as well as a diary to record their daily feelings related to fatigue. In session two (second cycle of chemotherapy treatment), the nurse and patient engaged in an open interview about treatment, side effects, and daily activities of the patient and discussed the diary notes. In session three (one month after the completion of treatment), the patient discussed with the nurse changes in fatigue perception throughout treatment using diary notes. A questionnaire was completed by both the intervention and control groups at sessions one and three. Only the intervention group completed the questionnaire at session two.

• Forty patients who were chemotherapy-naïve with colorectal or gastric cancer (experimental group:  n = 23, mean age = 58.5 years [range 32–74]; control group:  n = 17, mean age = 62.7 years [range 49–75]) were included.
• Patients were excluded if they had received previous cancer treatment; had presence of respiratory, cardiac, or hepatic dysfunction; had a learning disability; had central nervous system metastasis; and/or had received previous radiotherapy.

• Single site
• Comprehensive cancer center in Barcelona, Spain

Patients were undergoing the active treatment phase of care.

The study used an experimental, randomized, stratified design.

• Functional Assessment of Cancer Treatment (FACT)
• Diary notes

Fatigue levels were lower for the intervention group after the second session in comparison to baseline and remained steady after one month posttreatment. Fatigue levels remained stable for the control group at baseline to one month posttreatment. These differences were not statistically significant.

• The study had a small sample size; therefore, it was underpowered.
• The observed difference may not be only due to the nursing intervention and can be attributed to outside factors, such as the response to medical treatment.
• The nursing intervention was slightly different according to needs of participants about fatigue, and the nurse was not always the same for all three sessions.

To determine the clinical benefit of hyperbaric oxygen therapy on the management of bowel dysfunction in patients who receive radiation therapy to the pelvis

Study of patients with chronic gastrointestinal problems for greater than 12 months post radiation therapy in spite of optimal medical management. Patients received either hyperbaric oxygen therapy or sham.

• N = 84   
• AGE = 62 years
• MALES: 44%, FEMALES: 56%
• CURRENT TREATMENT: Radiation 
• KEY DISEASE CHARACTERISTICS: Past therapy with pelvic radiation for treatment of gynecologic, prostate, or anal cancer

• SITE: Multi-site   
• SETTING TYPE: Outpatient    
• LOCATION: U.K.

PHASE OF CARE: Late effects and survivorship

Double-blinded, sham-controlled, phase 3, randomized trial

• Inflammatory Bowel Disease Questionnaire (IBDQ)
• IBDQ rectal bleeding

No difference between treatment groups existed.

In this patient group, no improvement using hyperbaric oxygen versus sham occurred.

• Small sample (< 100)
• Intervention expensive, impractical, or training needs

Large randomized, phase 3 studies are required before any conclusions can be made about the use of hyperbaric oxygen in patients with bowel dysfunction after radiation therapy.

To examine the effects of interventions for the prevention, treatment, or both, of herpes simplex virus (HSV) in patients receiving treatment for cancer.

• Databases searched were Cochrane Oral Health Group’s Trials Register, CENTRAL, MEDLINE, EMBASE, CINAHL, CANCERLIT, SIGLE, and LILACS.
• Keywords searched were neoplasm, cancer, bone marrow transplant, herpes simplex or herpes labialis, and mucositis herpetic.
• All randomized, controlled trials (RCTs) compared interventions for the prevention or treatment or both of HSV infection in people being treated for cancer.  Published and unpublished studies were included in the searches.
• Articles were excluded if they were not RCTs, did not involve patients with cancer, and did not meet the inclusion criteria.

Forty studies were initially reviewed.

• After excluding studies due to the exclusion criteria, 17 studies remained for analysis.
• The sample size across studies ranged from 21 to 151.
• The majority of studies were conducted in patients with hematologic malignancies.  Only one study included patients with solid tumors.

• Acyclovir was more effective than placebo in the prevention of herpes infections whether given orally (relative risk [RR] = 0.11; 95% CI [0.05, 0.24]) or intravenously (IV) (RR = 0.24; 95% CI [0.07, 0.86]). No differences were found in effectiveness between oral or IV use or between adults and children.
• Valaciclovir appeared to be as effective as acyclovir in two relatively small trials for prophylaxis. In one trial comparing prostaglandin E to placebo, placebo was more effective in prevention than prostaglandin. In terms of herpes treatment, there were only two studies found and reported. Acyclovir was more effective than placebo in terms of time to healing (p = 0.01) and the duration of viral shedding was lower with acyclovir (p = 0.00008) compared to placebo.

The evidence suggested that acyclovir may be beneficial for the prevention and treatment of herpes infection in this patient population; however, the risk ratios were relatively small, suggesting limited benefit.  Valaciclovir may also be effective; however, few studies have reported this particular agent, so firm conclusions cannot be drawn. Prostaglandin E appears to have no benefit for the prevention of herpes infection in this group of patients. The degree of immunocompromised patients in study samples was not discussed, and sample sizes varied across studies, suggesting limited ability to truly generalize the findings provided here.  Acyclovir was more effective than placebo in the prevention of herpes infections whether given orally (RR = 0.11; 95% CI [0.05, 0.24]) or IV (RR = 0.24; 95% CI [0.07, 0.86]). No differences were found in effectiveness between oral or IV use or between adults and children. Valaciclovir appeared to be as effective as aciclovir in two relatively small trials for prophylaxis.

Fifteen trials evaluated the effect for prevention of herpes infection, and two trials evaluated herpes treatment.

The purpose of the study was to evaluate itraconazole solution or capsules compared with control (no treatment, placebo, oral polyenes, or fluconazole).

Searches were conducted through Cochrane Central Register of Controlled Trials and MEDLINE (January 1966 to July 2003); abstracts from the annual meetings of the American Society of Hematology, Interscience Conference on Antimicrobial Agents and Chemotherapy, European Hematology Association, European Group for Blood and Marrow Transplantation, German and Austrian Society of Hematology and Oncology, and the British Society for Hematology (1994–2003). Reference lists of relevant studies were reviewed. The pharmaceutical manufacturer of itraconazole was contacted.

13 randomized, controlled trials.

3,597 patients (1,812 on itraconazole and 1,785 controls) with hematologic malignancies who were neutropenic (absolute neutrophil count less than 500) following chemotherapy or bone marrow transplantation.

• A statistically significant decrease was found in the incidence of invasive fungal infections in the itraconazole solution group (49% reduction), but not in the itraconazole capsule group.
• A statistically significant decrease existed in the incidence of invasive yeast infections in the itraconazole solution group (60% reduction), but not in the itraconazole capsule group.
• A statistically significant decrease was found in the incidence of proven invasive aspergillus infections in the itraconazole solution group (48% reduction), but not in the itraconazole capsule group
• A statistically significant decrease was noted regarding mortality in the itraconazole solution group (42% reduction), but not in the itraconazole capsule group.
• No significant difference existed between the groups regarding mortality from any cause during the study period.

Antifungal prophylaxis with an itraconazole solution for neutropenic patients with hematologic malignancies reduces invasive fungal infections, invasive yeast infections, invasive aspergillus infections, and mortality. Bioavailability and dosing are significant factors because benefits are only derived from the oral or IV cyclodextrin solution and not the capsules.

The capsules are not recommended and the dosing should be at least 400 mg per day of the oral cyclodextrin solution or 200 mg per day of the IV solution.

To conduct a thorough systematic review of interventions aimed at families with chronically ill members and to describe and critically evaluate these interventions for caregivers of chronically ill persons

• PubMed MEDLINE, CINAHL, Cochrane Library, EMBASE, and PsycINFO (English only) databases were used. After the initial search, one additional search occurred in Web of Science, SocINDEX, Sociological Abstracts, and ERIC (no citations from the additional search were included).
• Key words were chosen based on predefined terms of each database, with main focus on the following words: intervention, caregivers, and diagnoses of diabetes, cardiovascular disease, cancer, or stroke.
• Studies included in the search addressed the selected diagnoses (stroke, cardiovascular disease, cancer, or diabetes) and were reviews and controlled studies published in English between 1997 and 2007.
• Studies that used patients younger than 18 years of age and dying adults were excluded.

• Forty-six studies were initially reviewed. Included in the report were 32 controlled studies (29 with randomization) described in 35 articles (stroke = 19, cancer = 10, cardiovascular disease = 3, and diabetes = 0). Study quality was addressed via author collaboration.
• Of the 32 studies, 12 were from the United States, and an additional 10 were completed in Western Europe. All patient with cancer/caregiver studies supported an international perspective.

• The final sample of 32 studies included 4,264 patients.
• Across studies, samples ranged from 30 to 1,040 caregiver/patient dyads.
• Very few studies addressed dropout rates and reasons for that occurrence.
• Participants were diagnosed mostly with stroke, then cancer, and least of all cardiovascular disease; no other information appears in the study information about samples.

Experimental interventions provided support to caregivers, patients, or both. Of the 32 studies, 4 interventions addressed caregivers alone and 32 interventions addressed both patients and caregivers. All experimental interventions included health professional–led discussion and guidance to increase knowledge, comfort, or resource allocation for persons addressed in the study. Educational delivery occurred at individual, couple, and group levels, and sessions occurred in a variety of inpatient and outpatient areas, including the patient’s/caregiver’s home. Half of the interventions involved home visits by a professional who taught, counseled, or helped a participant with practical home roles.

All studies involving patients with cancer or caregivers used hospital-based interventions and centered on alleviating physical and psychosocial concerns of patients with cancer. Although the focus of interventions was the same for patients experiencing stroke and cardiovascular disease, most interventions occurred in the home with a focus on caregiver well-being.

Educational interventions incorporated cognitive-behavioral therapy to support knowledge transfer that would improve participant well-being. Some studies compared different forms of an intervention (e.g., individual versus group), and some interventions included sites and telephone contacts. No studies considered or changed an intervention based on the participant’s social background. Professional actors of studies were mostly nurses and healthcare providers prepared at the bachelor's degree. The authors noted across disease groupings that interventions fit into the following areas: caregiver experience with burden, level of knowledge, skills mastery, and satisfaction.

Of 32 studies, 22 reported effects in one or more areas that the intervention targeted. Studies that showed a positive intervention effect mostly focused on caregiver burden and mastery of skills to provide care. However, the authors noted that it is not possible to support any consistency between interventions because many different instruments used in the 32 studies measured the same variable (e.g., 26 measures for depression).

The authors noted that the systematic review guides the following conclusions:

• There is a lack of knowledge supported by evidence about the effect of interventions on caregivers examined in this study; this inadequate level of evidence shows a need to challenge the quality of the studies.
• The effect of interventions targeting caregivers of chronically ill patients is inconclusive and recommendations on the type of intervention that would be most appropriate cannot be made. Few studies exist that document the effect of interventions on caregivers of chronically ill patients because most times the ill patient is the focus of the healthcare team. The few documented studies often lack sufficient rigor to support changed clinical practice for caregivers and the patients they serve.
• Interventions with a different, broader focus than short-term education or group dynamic process in a secondary healthcare setting should be considered.
• Further work should build on connections between randomized control studies with reliable and valid instruments and strong definition of an intervention that  may show significant intervention effects. This evidence will provide credible data for how to change and improve clinical practice.
• Additional qualitative work may inform understanding of ways health providers can create knowledge of caregivers through building on content and process of care already known to caregivers. This collaboration will allow tailoring of psychosocial and learning interventions for caregivers with unique histories and needs to support their health and ability to continue their caregiving role.

To evaluate the efficacy and safety of balugrastim compared to pegfilgrastim

Patients were randomized to receive either once per cycle 40–50 mg balugrastim or 6 mg pegfilgrastim by subcutaneous injection 24 hours after administration of chemotherapy. Blood samples were obtained twice weekly after post-nadir absolute neutrophil count (ANC) was greater than two, and temperature was measured twice daily.

• N = 238
• MEAN AGE = 49.9 years
• MALES: 0.04%, FEMALES: 99.6%
• KEY DISEASE CHARACTERISTICS: Patients with breast cancer. Approximately one-third had metastatic disease.
• OTHER KEY SAMPLE CHARACTERISTICS: Patients were excluded if they had received more than one prior chemotherapy cycle.

• SITE: Multi-site  
• SETTING TYPE: Not specified  
• LOCATION: Russia and Ukraine

• PHASE OF CARE: Active antitumor treatment

• Open-label randomized noninferiority trial

• Duration of severe neutropenia defined as ANC < 0.5 x 10⁹/L
• Incidence of febrile neutropenia (oral temp ≥ 38.2 C)
• Time to ANC nadir
• Duration and depth of ANC nadir
• Time to ANC recovery
• National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0

Difference in duration of severe neutropenia was less than one day between balugrastim and pegfilgrastim, and was similar in both dosages of balugrastim. Duration and incidence of severe neutropenia were reduced in subsequent cycles in all groups. There were no significant differences in incidence of febrile neutropenia. In cycle one, time to ANC recovery was shorted in the balugrastim group (2.0–2.1 days versus 2.6 days, p = 0.005). Adverse effects were similar in both groups. Presence of antibodies to the medication was similar in both groups.

A single fixed dose of balugrastim was not inferior to pegfilgrastim for management of neutropenia.

• Risk of bias (no blinding)

Balugrastim is an effective alternative to pegfilgrastim in patients with breast cancer receiving myelosuppressive chemotherapy. A single fixed dose per cycle was as effective as pegfilgrastim. Further research comparing various colony-stimulating factors (CSFs) and biosimilar agents are needed to continue to identify the most acceptable and cost-effective methods for hematopoetic support in patients receiving myelosuppressive chemotherapy with a high risk of febrile neutropenia.

To explore the effects of a prostate-specific program on physical activity, fatigue, mental distress, and quality of life (QOL).

Courses were conducted by a multidisciplinary team, including lectures, physical activity, and group sessions, lasting for six days. Activity was performed in groups of six to nine patients twice daily, including water gymnastics, walking, Nordic walking, resistance training, pelvic floor training, stretching, and relaxation for 60 to 90 minutes. Group sessions met for one hour daily and were led by a nurse with experience in group counseling. Lectures involved presentation of medical facts, treatment modalities, late effects, and social and other benefits of physical activity. Study measurements were obtained at baseline and at three-month follow-up.

• Sixty-eight patients (100% male) were included, and 51 completed the entire program. 
• Mean age was 67.4 years (range 48.5–81.2).
• All patients had prostate cancer.
• Of the patients, 14% had metastatic disease, 43% had undergone surgery and radiotherapy, 20% had received radiotherapy, and 16% had received hormonal therapy.
• Median time since diagnosis was 18.2 months.
• Most patients were retired, 50% had completed college education, and 86% were married or cohabitating.

• Single site
• Inpatient
• Norway

Patients were undergoing the active treatment phase of care.

This was a prospective, observational study.

• Godin Leisure-Time Exercise Questionnaire
• Fatigue Questionnaire (physical score range 0–21; mental score range 0–12)
• Memorial Anxiety Scale for Prostate Cancer (MAX-PC)
• Hospital Anxiety and Depression Scale (HADS)
• European Organization for Research and Treatment of Cancer Quality of Life (EORTC QLC-C30 QOL) scale

Total fatigue scores declined from 16.1 to 14.0 (p = 0.001), and physical fatigue declined from 11.1 to 9.2 (p = 0.001). Those who did not complete the entire program had higher baseline fatigue scores. Anxiety results were mixed:  anxiety declined on the prostate specific measure (p = 0.001), but there was no change on the HADS scale. QOL measures did not change significantly.

Although there was a significant reduction in fatigue, the degree of change was small (2 of 33 points possible). The study did not provide strong support for the effectiveness of this program.

• The study had a small sample size, with less than 100 patients.
• No control or comparison group was used.
• The sample was highly variable in terms of the age range, and the rehabilitative needs of younger patients who may have undergone curative surgery can be expected to be different than those of older patients; this was not analyzed.
• Use of an inpatient setting for six days for this type of program can be expected to be expensive.
• Time from surgery to study entry varied, and final measures were three months after the program, with no interim assessment; it is not clear what the best timing of such interventions are in the disease trajectory.
• There was no information regarding continued activity prior to the final study measures being obtained.

The results suggested a small effect of this type of program on fatigue and no significant impact on overall anxiety or QOL.