200 mcg of misoprostol or placebo was dissolved in 15 ml of water. Patients swished in oral cavity for two minutes, then swallowed. Patients were advised to gargle before swallowing.

The study was comprised of 83 patients with squamous cell carcinoma of the head and neck, older than 18 with a total radiation dose higher than 50 Gy.
Misoprostol arm: n = 42
Placebo arm: n = 41
 

1999–2002

Double-blind, placebo-controlled, randomized trial

Extent of RTOG grade 3 mucositis (incidence and duration).

Secondary endpoints were time to development of mucositis, extent of grade 2 mucositis, patient weight, general well-being using VAS, and oropharyngeal or oral soreness.

RTOG, VAS
 

No significant differences were found for endpoints. More patients in the misoprostol arm reported increased levels of oral or oropharyngeal soreness.

Did not accrue adequate patients according to statistical analysis.

12% patient withdrawals

To evaluate short- and long-term effects of different exercise parameters during adjuvant treatment on cancer-related fatigue.

Databases searched were CINAHL, EMBASE, MEDLINE, Scopus, PEDro, and Cochrane Library to 2008. Hand searching was performed using reference lists from articles obtained.

Search keywords were cancer (and related terms), chemotherapy, radiotherapy, hormone*, exercise, cycle, train*, walk, and fatigue.

Studies were included in the review if 

• They were randomized, controlled trials
• They studied effects of exercise on cancer-related fatigue in adults receiving adjuvant therapy
• There was overlap of 50% or more of the exercise intervention with the cancer treatment period
• The study compared exercise with a no exercise usual care group
• Patient-reported fatigue was the outcome.

No exclusion criteria were specified.

Initally, 1,097 articles were identified. A final set of 18 articles met the inclusion criteria. The PEDro scale was used to rate the methodological quality of the research. Fifteen studies were considered to be of high quality, with a score 4 or greater (range 2–8).

• The final sample of 18 studies involved 1,109 patients.
• Study sample sizes ranged from 14 to 174 patients.
• Twelve of the 18 studies were performed in patients with breast cancer.

Overall Findings in Breast Cancer

• Pooled results in patients with breast cancer (n = 654) showed a small significant reduction in fatigue with exercise (standardized mean difference [SMD] = 0.22; 95% confidence interval [CI] [0.06, 0.37]; Z = 2.46; p = 0.01).

Home-Based Exercise

Exercise was home-based and self-monitored in seven studies. Interventions consisted of walking for 10 to 45 minutes per week and for three to six times per week. In one study, the participants also performed resistance exercises. Cancer treatments and timing of the programs varied. Adherence ranged from 70% to 100%.

• Pooled results of 2 high-quality studies (n = 128) showed a small nonsignificant reduction in fatigue (SMD = 0.10; 95% CI [-0.25, 0.45]).

Supervised Exercise Programs

Supervised programs were used in five studies. Three involved aerobic exercises, and the others included groups with stretching and/or resistance exercises. Most were performed for 10 to 30 minutes three times per week. Programs were completed by 39% to 100% of partcipants.

• Pooled analysis of three high-quality studies (n = 340) showed a medium significant reduction in fatigue with exercise (SMD = 0.30; 95% CI [0.09, 0.51]).

Overall Findings in Prostate Cancer

Four studies were performed in patients with prostate cancer; three were supervised and one was home-based.

• Pooled results in these five studies showed a medium significant reduction in fatigue with exercise (SMD = 0.32; 95% CI [0.05, 0.59]).
• Subgroup analysis of home-based and supervised programs showed small nonsignificant effects, with these approaches analyzed individually.

Findings in Multiple Myeloma and Acute Myeloid Leukemia

One study was performed in each of these patient groups. One was of low quality. Both had nonsignificant reductions in fatigue.

Only short-term effects could be analyzed because only one study described any longer-term effects of physical exercise. No significant adverse effects overall were seen. Supervised aerobic exercise programs were more effective in reducing fatigue than home-based programs. There were significant positive effects during breast cancer treatment, with small to moderate effect sizes. The most effective frequency intensity or duration of exercise could not be determined. Reported adherence to the exercise program varied widely.

• There was an overall beneficial effect of exercise in patients with prostate cancer when all findings were pooled; however, the effectiveness of home-based and supervised programs could not be demonstrated separately.
• The limited number of studies and available data in this area may have influenced these results.
• The clinical relevance of findings could not be determined due to the wide range of measurement instruments used in the research and the lack of associated data that establish clinically important differences.

Findings showed that exercise had at least a small beneficial effect in reducing fatigue for patients during adjuvant treatment. Supervised programs may be more effective than self-managed home-based programs. More research on the effects of resistance exercise, home-based exercise, and most effective exercise parameters are needed. Longer-term outcomes and patient adherence need to be examined further. Research on the effects of exercise in other patient types is also needed.

To compare the effectiveness of two antifungal prophylaxis regimens in the setting of hematopoietic cell transplantation (HCT)

The study compared patient outcomes between patients undergoing HCT who received only 200 mg posaconazolel three times daily for 100 days to those who also received intermittent IV micafungin at 50–100 mg. Micafungin was provided for patients who were unable to take the oral medication for any reason. The decision to switch to micafungin was at the physician’s discretion.

• N = 212
• MEAN AGE = 46.7 years
• MALES: 58%, FEMALES: 42%
• KEY DISEASE CHARACTERISTICS: Most patients undergoing HCT had acute leukemia or lymphoma.

• SITE: Multi-site  
• SETTING TYPE: Multiple settings    
• LOCATION: Germany

PHASE OF CARE: Active antitumor treatment

• Retrospective

• Incidence of proven or probable invasive fungal infection (IFI) defined according to European Organization for Research and Treatment of Cancer and the Mycoses Study Group (EORTC/MSG)
• Febrile neutropenia defined as incidence of fever not responsive to antibiotics for at least 72 hours.
• Pneumonia—fever with positive diagnostic imaging

Mean number of febrile days was 5.9 in the posaconzole group and 4.3 in the group also receiving micafungin (p = 0.051). The number of possible IFI in the group receiving micafungin bridging was significantly lower (16% versus 3.8%, p = 0.005). Those receiving micafungin bridging had higher fungal-free survival at 100 days post-HCT (p = 0.009). There was no difference in overall survival between groups.

Use of IV micafungin in patients unable to take oral posaconazole was effective in reducing fungal infections.

• Risk of bias (no random assignment)

This study shows that intermittent use of IV micafungin was effective for patients unable to take oral posaconazole for antifungal prophylaxis following HCT. Both of these regimens were shown to be feasible and effective. Further research in this area is warranted to determine most effective drug combinations and timing to prevent breakthrough IFI.

To compare caspofungin and itraconazole as secondary prophylaxis in patients with hematological malignancies.

Physicians completed case report forms via the intranet for data collection and analysis.  Physicians did not follow any specific protocol, drug selection was based upon individual discretion and timing, and dosages of medications used varied. Outcomes were assessed at the end of neutropenia.

• Seventy-seven patients (64% male, 36% female) were included.
• Average age was 48.5 years (range 16–72).
• Seventy percent of patients did not undergo transplantation.  Most of the remaining patients underwent allogeneic stem cell transplantation.

• Multi-site  
• Inpatient 
• Germany

Patients were undergoing the active antitumor treatment phase of care.

This study was observational.

• European Organization for Research and Treatment of Cancer (EORTC)/Mycoses Study Group (MSG) criteria for diagnosis and assessment of first and breakthrough invasive fungal disease (IFD)
• Complete response (defined as a disappearance of all clinical, microbiological, and radiographic evidence of infection)
• Partial response (defined as >50% radiographic signs of infection).

Incidence of breakthrough IFD was similar in both groups of patients (31.9%–32.1%). There were no significant differences between groups in any other outcome measures.  Death attributable to IFD ranged from 3.6% to 4.3%. Aspergillosis was the most frequent infection, followed by candidiasis.  Overall mortality was 16%.
 

No differences were found in efficacy between these two medications; however, no conclusions could be drawn due to multiple study limitations and significant differences between patient groups in the sample.

• Small sample (<100)     
• Baseline sample/group differences of import   
• Risk of bias (no control group, no blinding, no random assignment, sample characteristics*) 
• Key sample group differences that could influence results*
• Measurement validity/reliability questionable*

*Substantial variability in patient characteristics that would influence findings, variability in methods of treatment, other measures used for infection prevention, etc.

This study provided no evidence to differentiate the efficacy between these two medications for secondary antifungal prophylaxis.

To compare the effects—on quality of life and symptoms of depression—of an intervention consisting of a psychotherapeutic intervention, narrative therapy, plus escitalopram to the effects of usual care plus escitalopram

The initial sample was composed of 1,026 patients, between March 2006 and June 2008, with a diagnosis of breast, lung, or colorectal nonmetastatic cancer, three months after cancer diagnosis and no later than two years after diagnosis. Investigators used the Hospital and Anxiety Depression Scale (HADS) to screen participants for depression. A total of 150 had depressive disorder according to DSM-IV-TR criteria. The study contained 72 participants, 33 in usual care and 39 in combined care. Escitalopram was administered on a fixed-flexible schedule in both groups, beginning with 10 mg per day and adjusted up to 20 mg per day by week 8. A minimum of six months treatment was established for both groups. The narrative intervention was carried out individually during 12 weekly sessions, each 45 minutes long, and was guided by a treatment manual. Of the sessions, 10% were videotaped to help ensure adherence. Usual care consisted of oncologist-adminstered antidepressant. The oncologist followed a protocol and reported side effects of the medication. The follow-up of patients in the usual-care group was similar to that of patients in the treatment group. Investigators assessed depression-related outcome at weeks 12 and 24.

• The sample was composed of 72 participants. At the 12-week assessment, the sample contained 68 participants. At the 24-week assessment, the sample contained 56 participants.
• Mean patient age was 54.6 years (SD = 10.4 years). The age range was 35–75 years.
• The sample contained 19.4% males and 80.6% females.
• Participants had lung, breast, or colorectal nonmetastatic cancer and major depressive disorder, single-episode or major recurrent depressive disorder, or adjustment disorder with depressed mood, or adjustment disorder with mixed anxiety and depressed mood.
• Participants had a life expectancy longer than one year and a Karnofsky Performance Status Score of 70 or higher. Participants were receiving ambulatory care and had depressive disorder according to DSM-IV-TR criteria.
   

• Multisite
• Outpatient
• Madrid, Spain

• Phases of care: multiple
• Clinical applications: late effects and survivorship

Two-center randomized controlled trial

• European Organization for Research and Treatment Cancer Core Quality of Life C30 (EORTC QLQ-C30), a self-rating scale that measures quality of life. Thirty items evaluate five functional domains and three scales of symptoms. Five items assess common physical symptoms of cancer. Other items assess global health, global quality of life, and the perceived financial impact of disease and treatment. Scores are 0–100. The EORTC QLQ-C30 has been validated for use by Spanish patients with cancer.    
• Hospital anxiety and depression scale (HADS). Investigators used this scale at baseline, for screening, and at 12 and 24 weeks. HADS is a 14-item self-rating scale that measures anxiety and depression and is designed specifically for patients with physical illness. A score of 11 or more indicates probable psychological morbidity; a score of 8–10 indicates possible psychological morbidity. The scale has been validated for use by Spanish patients.

Demographic variables did not differ significantly between the two groups. Gender and age were unbalanced because of cancer types. At 12 and 24 weeks, the combined-therapy group showed significantly greater improvement in all the dimensions of function (p < 0.01), pain scale (p = 0.02), global health (p = 0.02), and global quality of life (p = 0.007). Between groups there were no statistically significant differences in symptoms of depression. From week 12 to 24, study retention was higher in the combined-treatment group (p = 0.01).

Using combined therapy for major depression in patients with cancer results in significant improvements in quality of life but does not result in a significant reduction in symptoms of depression. Narrative therapy is an integrative intervention designed to address components of critical importance in patients with depression. The therapy may have a positive impact on patient’s fears and worries about medication interactions and side effects.

• The study had a small sample size, with fewer than 100 participants.
• Types of cancer were not evenly distributed between groups.
• The study used interim analysis to estimate statistical power and sample size.
• A different specialist administered the drug.
   

The interventions proved to be acceptable to patients. The intervention shows good potential for dissemination, is relatively easy to implement, and improved compliance. The intervention may be a low-cost means of improving the quality of life of patients with cancer.

To determine if a mouthwash containing morphine decreases oral pain associated with chemotherapy- or radiotherapy-induced mucositis

Subjects were randomized to two groups. One used 2% morphine solution. The other used a placebo, a quinine solution. Both groups used the specified solution six times daily, holding the solution in the mouth for 2 minutes at each application. After three days patients crossed over to the alternate treatment. Patients kept daily diaries and rated oral pain before and one hour after the mouthwash. The study lasted six days.

• The sample was composed of 11 patients.
• Mean patient age was 55.1 years (SD = 3 years).
• The report did not state the percentages of males and females in the sample.
• The report did not state key disease characteristics.
• All patients were receiving either chemotherapy or radiotherapy. Most patients used acetaminophen and NSAIDs for pain; three patients used opiods.
   

• Multisite
• Clinical
• Switzerland
   

Phase of care: active treatment

Randomized double-blind crossover study

The study used a 10 cm visual analog scale (VAS), to rate pain.

ANOVA suggested a difference over time between placebo and morphine, but authors noted no significant differences in pain between mouthwashes on the same or different days. Not all patients adhered to prescribed frequency of use. Authors noted no adverse events.

Study results did not support the use of morphine mouthwash as a treatment for the pain of oral mucositis.

• The study had a small sample size, with fewer than 30 patients.
• The study had a risk of bias resulting from sample characteristics.
• Other possible study limitations were short duration; low pain levels, given the medications used; and lack of information about rescue medication. The study did not consider how many subjects may have been receiving multiple treatments, a factor that might have affected mucositis. The frequency of mouthwash use, to achieve effective pain relief, is unknown.

This study was too small to demonstrate the effects of a morphine-containing mouthwash on mucositis-associated oral pain.

To investigate the effectiveness of silver leaf dressings in treating radiation-induced dermatitis compared with the current standard of care (silver sulfadiazine).

Patients presenting with grade 2 or greater skin toxicity within radiation portals were offered the topical treatment of silver sulfadiazine (application three times daily and removed prior to daily radiation) and silver leaf dressing worn constantly (removed only for radiation treatments).

Each patient applied silver leaf dressing on one side of the neck and silver sulfadiazine on the other.

Silver leaf dressing and silver sulfadiazine were each assigned randomly to each side of the patient’s neck.

• Twelve patients were entered, and five completed the study.
• Age and gender were not reported.
• Patients had squamous cell carcinoma of the base of the tongue, tonsillar fossa, oropharynx, hypopharynx, or larynx.
• Radiation doses varied from 60 Gy in 30 fractions to 72 Gy in 42 fractions.
• The majority of patients received 70 Gy in 35 fractions.
• Five of the 12 patients received concurrent platinum-based chemotherapy.

The study used a quasiexperimental design; patients were used as their own controls.

• Patients were evaluated weekly (or more) by a treating physician. At evaluations, patients were questioned regarding quality of pain control by the treating physician and an independent research coordinator.
• Radiation Therapy Oncology Group (RTOG) acute skin toxicity scoring system was used to grade dermatitis.
• Digital photographs were taken to establish baseline skin status, as well as for follow-up during and after.
• Three physicians were presented with digital photographs and were asked to evaluate and grade skin toxicity, as well as compare both sides of the head and neck of patients.

• No difference in improvement was reported between the control and test sides in any patient with regard to RTOG grade throughout the duration of application of both modalities. However, within the same grade, two of three observers agreed on some degree of improvement in dermatitis with silver leaf dressing compared with silver sulfadiazine.
• Eight of the 12 patients (67%) subjectively reported improved pain control on the side treated with silver leaf dressing.
• Seven of the 12 patients (58%) on the silver leaf dressing treatment side presented with smaller regions of same-grade dermatitis with a tendency toward faster healing.
• Four of the 12 patients (33%) had equivalent results with both treatment modalities.
• Duration of healing varied between 7 and 28 days.
• Within the same RTOG grade, sliver leaf dressing appeared to provide greater relief of pain and greater skin condition.

Silver leaf dressing does not appear to be superior to standard treatment for radiation-induced dermatitis when the RTOG grading system is used.

• The study had a very small sample, and less than one-half of patients completed the study.
• No formal pain assessment scale was consistently used during pain assessment.
• The potential impact of concurrent chemotherapy on healing could not be evaluated or discussed.
• Because of the subjective nature of evaluation of dermatitis within RTOG grade, the opinion of the majority of observers served to classify response of dermatitis. It would be more reliable to have averaging of observations.
• The study lacked strict guidelines to ensure conformity to treatment.

10-week CBSM

• N = 240
• MEAN AGE = 50.99 years for CBSM and 49.69 years for psychoeducational control group 
• FEMALE: 100%
• KEY DISEASE CHARACTERISTICS: Patients with early-stage breast cancer (stage III and below) who had completed surgery (lumpectomy or mastectomy) prior to randomization

• SITE: Not stated or unknown  
• SETTING TYPE: Not specified  
• LOCATION: Southern Florida

• PHASE OF CARE: Active anti-tumor treatment

• Experimental (random assignment)

• Pittsburgh Sleep Quality Index (PSQI)
• Fatigue Symptom Inventory (FSI)

No statistical differences in PSQI total scores or changes in fatigue intensity between groups. Changes in sleep quality were associated with change in fatigue.

CBSM may have some positive effects on elements of sleep quality and fatigue. Data support an association between sleep quality and fatigue (fatigue-related daytime interference).

• Risk of bias (no appropriate attentional control condition)
• Risk of bias (sample characteristics)
• Key sample group differences that could influence results
• Intervention expensive, impractical, or training needs
• Questionable protocol fidelity
• Subject withdrawals were 10% or greater

Consider evaluation of sleep disturbance in patients experiencing fatigue.

STUDY PURPOSE: To review the evidence for opioids in the treatment of dyspnea in patients with cancer

TYPE OF STUDY: Systematic review

• FINAL NUMBER STUDIES INCLUDED = 14 
• TOTAL PATIENTS INCLUDED IN REVIEW = 247
• SAMPLE RANGE ACROSS STUDIES: 9–70
• KEY SAMPLE CHARACTERISTICS: Lung and breast cancer were the most common. Other tumor types were included.

PHASE OF CARE: Not specified or not applicable
 
APPLICATIONS: Palliative care

• Morphine was examined in nine studies. All showed positive effects of morphine on dyspnea at rest or exercise, given by oral or subcutaneous routes.
• Hydromorphone was examined in five studies. Most were nonrandomized studies, and all showed benefit in opioid-naïve and opioid-treated patients.
• Fentanyl was examined in three studies. Mixed results were reported.
• No respiratory depression episodes were reported with the use of opioids.

Overall, opioids were seen to be beneficial in reducing dyspnea.

• Limited search
• Limited number of studies included
• Low sample sizes

This review adds to the body of evidence regarding the efficacy of opioids for the management of dyspnea in patients with cancer. Morphine is the most frequently studied opioid.

The study aim was to evaluate the comparative safety and effectiveness of fluconazole versus itraconazole as primary prophylaxis in neutropenic patients with cancer. The main outcomes of the study were withdrawals from the studies because of adverse effects, documented fungal infections, invasive fungal infections, differentiation between mold and yeast invasive infections, and overall mortality. Secondary outcomes were total fungal infections, suspected fungal infections, superficial fungal infections, and mortality attributed by the authors of each randomized, controlled trial (RCT) to fungal infections.

PubMed (until March 2005), Current Contents Connect, and the Cochrane Central Register for Controlled Trials databases were searched, as were the references from relevant articles, including review papers, to identify relevant RCTs. Two independent reviewers performed literature searches and examined the identified relevant RCTs for evaluation of data on toxicity and effectiveness.
   

Search terms included prophylaxis, prevention, antifungal, azoles, fluconazole, itraconazole, ketoconazole, miconazole, clotrimazole, neutropenia, granulocytopenia, bone marrow transplantation (BMT) and stem cell transplantation (SCT)
   

A study was considered eligible if it was an RCT, it compared the effectiveness of prophylactic fluconazole with prophylactic itraconazole in neutropenic patients, and it assessed toxicity, effectiveness of azoles, or mortality. Concurrent use of topical antifungal agents, such as nystatin or amphotericin B, were permitted. The administration of IV amphotericin B was not permitted unless an invasive fungal infection was documented or suspected.

RCTs comparing the effectiveness of fluconazole or itraconazole with placebo or no treatment or polyenes were excluded. RCTs comparing other azoles also were excluded.

Seven refernece were retreived.

Statistical analyses were performed using meta-analyst software. The heterogeneity between RCTs was assessed by using a chi-square test; a p value lower than 0.1 was defined to note statistical significance in the analysis of heterogeneity. Publication bias was assessed by the funnel plot method using Egger’s test. Pooled odds ratios (OR) and 95% confidence intervals (CIs) for all primary and secondary outcomes were calculated, by using both the Mantel-Haenszel fixed effects and the DerSimonian-Laird random effects models. Results from the fixed effects model are presented only when no heterogeneity between RCTs was observed; otherwise, results from the random effects model are presented. A methodologic quality assessment of each trial was performed. Details of randomisation, the use of double blinding, handling of withdrawals, concealment of allocation, and generation of allocation sequences were awarded one point, for a maximum achievable score of five points. High-quality RCTs scored more than two points, while low-quality RCTs scored two or less points, according to the reported methodology.

• Five total studies were reviewed.
• Sample sizes per article ranged from 59–581.
• Key characteristics indluded neutropenic patients with cancer treated with fluconazole or itraconazole for the prevention of fungal infections.

Active treatment

No statistically significant differences were noted between prophylaxis with fluconazole and itraconazole regarding documented fungal infections (OR = 1.51, 95% CI [0.97, 2.35], five RCTs), invasive fungal infections (OR = 1.44, 95% CI [0.96, 2.17], four RCTs), development of mold infections (OR = 1.36, 95% CI [0.83, 2.24], four RCTs), development of yeast infections (OR = 2.28, 95% CI [0.92, 5.666], three RCTs), and all-cause mortality (OR = 0.89, 95% CI [0.63, 1.24], five RCTs).

Prophylactic use of fluconazole resulted in significantly more fungal infections (OR = 1.62, 95% CI [1.06, 2.48], four RCTs). However, no statistical difference was noted between fluconazole and itraconazole in the development of suspected fungal infections (OR = 1.23, 95% CI [0.74, 2.02], four RCTs), superficial fungal infections (OR = 1.49, 95% CI [0.67, 3.31], three RCTs), and mortality attributed by the authors to fungal infections (OR = 1.3, 95% CI [0.75, 2.25], five RCTs). Significantly fewer patients were withdrawn from the studies due to the development of adverse effects with fluconazole prophylaxis when compared with itraconazole (OR = 0.27, 95% CI [0.18, 0.41], five RCTs). Gastrointestinal complaints were the most common reason for withdrawal from the studies because of adverse effects. The main reason for withdrawal from the RCTs because of an adverse effect was hepatic or renal dysfunction.

Fluconazole was associated with slightly more fungal infections, but there was no difference in mortality between fluconazole and itraconazole, and fluconazole was associated with fewer adverse effects.

Fluconazole and itraconazole are both effective for primary antifungal prophylaxis.