To evaluate the effect of anterior ultrasound-guided superior hypogastric plexus neurolysis in patients with gynecologic cancer with pelvic cancer pain

Patients were randomly divided into two groups. Group 1 received oral morphine for pain control, and group 2 had ultrasonography-guided superior hypogastric plexus neurolysis (SHPN). Oral morphine was given to both groups as rescue analgesia. The pain, functional capacity, global satisfaction score, and adverse effects were recorded.

• N = 50  
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Advanced gynecologic malignancy (stage III and IV), no planned curative intervention or chronic pelvic pain, visual analog scale (VAS) score greater than 7
• EXCLUSION CRITERIA: Unstable cardiovascular, respiratory, hepatic, or hematologic disease; psychological disorder; lower limb neurologic disorder; drug abuse

• SITE: Single site   
• SETTING TYPE: Inpatient   
• LOCATION: Rotary Cancer Hospital, New Delhi, India

• PHASE OF CARE: Multiple phases of care
• APPLICATIONS: Elder care, palliative care

• Randomized, controlled trial

• VAS
• Eastern Cooperative Oncology Group (ECOG) status
• Global pain relief score
• Global satisfaction score

No difference was seen between the two groups when comparing age, height, and wight (P > 0.05). Both groups showed a significant decrease in VAS pain sores at one week, one month, two months, and three months, and from baseline at each visit (P < 0.05). At three months, no significant difference was seen in VAS scores. No statistical difference was seen in baseline morphine consumption. Consumption declined from baseline in group 2 at the first week, but consumption increased at the rest of the time points. At the first week and month, rescue doses of morphine differed but not significantly for the last two visits. At week one, ECOG status was significantly better for group 2 (p = 0.002), and global pain was better at one month (p = 0.008), but by the end of the study, no statistical difference was seen. The global satisfaction score was better at dthe first week (p = 0.00) and first month (p = 0.04). Less adverse effects occurred in group 2 than group 1, but the difference was not statistically significant.

Ultrasonography-guided SHPN may be a potential intervention for patients with gynecologic cancer experiencing pelvic pain. This may be an option for those who cannot tolerate opioids or are experiencing adverse effects from long-term use of opioids. Although this intervention requires prep and fasting and is associated with its own adverse effects and risk, this may be an option for intervention. This study does not appear strong enough to replace opiate as the standard but rather supports the intervention as an adjuvant treatment because a portion of patients with cancer may be resistant to traditional therapies.

• Small sample (less than 100)
• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Findings not generalizable
• Other limitations/explanation: The intervention requires a certain amount of expertise to perform, can be associated with several adverse effects, is invasive, and requires bowel prep and the patient to fast for eight hours.

Nurses need to be aware of this potential intervention and management of adverse events in practice. Education would be required to manage adverse effects and side effects of this intervention.

To conduct a meta-analysis of the effectiveness of exercise interventions on health-related quality of life (HRQoL) and domains (e.g., physical, psychological, economic, social, and spiritual well-being) of HRQoL among adult cancer survivors posttreatment.

Databases searched were Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, MEDLINE, EMBASE, CINAHL, PsycINFO, PEDro, LILACS, SIGLE, SPORTDiscus, OTSeeker, Sociological Abstracts, Web of Science, and Scopus.

Search keywords (selected from appendices) were exercise, quality of life, health-related quality of life, pain, and cancer.

Studies were included in the review if they

• Were randomized, controlled trials (RCTs) and controlled clinical trials that compared exercise interventions with either usual care or no exercise
• Evaluated the impact on overall HRQoL or at least one domain of HRQoL in cancer survivors posttreatment
• Reported cancer survivors diagnosed as adults (18 years and older).

Studies were excluded if they reported patients with terminal cancer or in hospice care who were receiving active treatment for primary or recurrent cancer.

A total of 1,795 relevant references were retrieved.  A total of 1,636 articles were excluded based on the title and abstract.  After further review of the abstract, 82 were excluded because they did not meet the inclusion criteria. An additional 13 were excluded from qualitative synthesis because they were ongoing studies.

• The review included a final number of 40 trials in qualitative synthesis and 33 in quantitative (meta-analysis of findings).
• A total of 3,694 participants were randomized to an exercise (n = 1,927) or control (n = 1,764) group.
• Of the 40 studies, 38 were RCTs, three used variation of an RCT, and two used a quasiexperimental design. All but four trials were randomized to an exercise group or a control group.
• Studies included various cancer types, including breast, colorectal, head and neck, and others. Twenty-two trials were focused on breast cancer only.
• The time frame included 30 studies completed with treatment and 10 completed during and after cancer treatment. Only posttreatment data were included. The range of treatment time was immediate completion of treatment to up to 15 years after completion.
• The majority of trials reported females only; 15 used mixed gender samples.
• Participant age ranged from 39 to 68 years.
• Of those reporting socioeconomic status, the majority of participants had at least a high school education.
• Fifteen trials reported past exercise use, with types of exercise including strength and resistance training, walking, cycling, yoga, qigong, and tai chi.

The review has clinical applicability for late effects and survivorship.

Exercise had a positive effect on change in HRQoL scores at 12 weeks and six months of evaluation, and it improved cancer-specific HRQoL in breast cancer concerns. The effect on HRQoL remained after exclusion of patients who were receiving active treatment. For cancer-specific HRQoL, there was significant improvement in exercise groups compared with controls for breast cancer concerns at baseline to 12 weeks and six months. There was a significant decrease in anxiety in the exercise group compared to controls at 12 weeks only (standardized mean difference [SMD] = -0.26; 95% confidence interval [CI] [-0.44, -0.07]) but not in breast cancer-only analysis. There was a high risk of bias in most of these studies, and when these were removed, the results were not significant. Significant differences were noted in body image at follow-up (12 weeks to six months and beyond) using the Rosenberg Self-Esteem Scale. Significant change scores were noted for cancers other than breast for improving depression scores (SMD = -0.46; 95% CI [-0.72, -0.19]). Significant improvements were noted in emotional well being (12 weeks) and fatigue (12 weeks and 6 months) (SMD = -0.42; 95% CI [-0.83, -0.02]). No effects after six months were seen for fatigue, and effects were not significant when studies involving patients during treatment were excluded. Improvement in pain using follow-up scores (12 weeks) was seen (SMD = -0.29; 95% CI [-0.55, -0.04]), but this was from a single trial. Positive effects were noted in sexuality scores at six months and sleep disturbance at 12 weeks (sleep SMD = -0.46; 95% CI [-0.72, -0.20]). Significant improvements were noted in change scores for social functioning (12 weeks and six months). No significant changes were noted in cognitive function, general health perspective, role function, and spirituality in exercise trials.

Exercise interventions showed beneficial effects on HRQoL and some HRQoL domains, including breast cancer concerns, body image, emotional well being, sexuality, sleep disturbances, social functioning, anxiety, fatigue, and pain at various follow-up time points.

• Studies included used exercise programs of various types, intensity levels, and lengths.
• Significant effects found tended to be in subgroups of patients or at only one time point, limiting the confidence in observed effects.
• Measures of HRQoL varied, creating heterogeneity among the studies in how HRQoL was quantified.
• There was a high risk of bias in the trials reviewed. In many cases, no significant effects were seen when analyzing changes in symptoms from baseline to follow-up time points, and significant findings were seen in comparing only follow-up scores between various comparison groups. Results should be used with caution for these reasons.

Findings supported the general benefit of exercise for patients with cancer; however, there is further need for research to verify the positive effects of exercise on symptoms of cancer in various patient groups and at various phases of cancer care. These future research studies should determine how to produce larger effect sizes over time and delineate predictors of that effect, such as type of exercise, intensity of the program, timing, and type of cancer and treatment in order to maximize the effect on QoL. It will be important to note that certain questionnaires can affect the outcomes, and consistency would improve this body of research.

PURPOSE: To evaluate the effectiveness of exercise interventions on several domains of health-related quality of life

• FINAL NUMBER STUDIES INCLUDED = 40 in systematic review (33 in meta-analysis)
• TOTAL PATIENTS INCLUDED IN REVIEW = 3,694
• SAMPLE RANGE ACROSS STUDIES: 7–271 patients
• KEY SAMPLE CHARACTERISTICS: Multiple tumor types

PHASE OF CARE: Late effects and survivorship

Studies included those with interventions such as yoga, tai chi, and qigong, as well as more traditional exercises. Moderate to vigorous exercise was associated with positive effects on quality of life (SMD = 0.29, 95% CI = 0, 0.58), but no effect was seen for mild to moderate level exercise. These findings did not differ by type of cancer. Anxiety was reduced in all studies by 12 weeks, but this was not observed at longer follow-up periods. At 12 weeks, more vigorous exercise showed no overall effect on anxiety with pooled data. However, a significant effect was seen with mild to moderate exercise (SMD = -0.26, 95% CI = -0.02,-0.51). For fatigue, there were significant positive effects at 12 weeks and between three and six months, but not at six months

The findings of this review show the benefits of various types of exercise on anxiety, fatigue, and quality of life among cancer survivors. Results varied by exercise intensity and at various time points in patient follow-up. This suggests that benefits exist mainly in the short-term up to six months.

Most studies showed a moderate to high risk of bias. All types of exercise were combined with various mind/body interventions, which would affect the results of the meta-analysis. It is not clear that these various types of interventions are truly equivalent types of interventions. The methods of measurement for the studies included were not provided, and differences in measurement would affect the meta-analysis. The search result volumes differed in two areas of this report. The differences reported by exercise intensity are confusing. It is not clear how more vigorous exercise improved quality of life while less vigorous exercise only affected anxiety.

Overall findings confirm other findings that exercise is beneficial for patients with cancer at various phases of care. This particular analysis was aimed at cancer survivors who completed initial treatment. It is of interest that the benefits of interventions appear to wane around the six-month timeframe. It is not clear if the interventions were done in a group setting for some time period or if social interaction could have influenced the findings that long-term effects were not generally seen if group exercise activity had ceased. Future research in this area should incorporate data to facilitate our understanding of the longevity of effects and mechanisms to maintain improvements long-term.

To determine the proportion of patients achieving complete control during the overall study period and continued for 24 hours after the last dose of chemotherapy, and to determine the proportion of patients achieving complete control within each 24-hour interval of observation

The first 50 patients received ondansetron plus dexamethasone. The experimental group received 0.25 mg IV palonosetron 30 minutes prior to chemotherapy on day 1, then every other day for the duration of the high-dose chemotherapy. Patients also received daily dexamethasone and omeprazole. The rescue medication was metoclopramide for any emesis or if the patient requested the medication. Nurses obtained data from the patients, including subjective nausea assessment every 24 hours and any episodes of emesis or use of rescue medication. Chemotherapy regimens included several myeloablative and non-myeloablative regimens.

• N = 108   
• AGE = 20–76
• MALES: 67%, FEMALES: 33% 
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Non-Hodgkin lymphoma, Hodgkin disease, breast cancer, testicular cancer, sarcoma
• OTHER KEY SAMPLE CHARACTERISTICS: Alcohol consumption, chemotherapy type (melphalan versus cytarabine versus other regimens)

• SITE: Single site   
• SETTING TYPE: Inpatient    
• LOCATION: Milan, Italy

PHASE OF CARE: Active antitumor treatment

Exact single-stage design using a historical cohort

Nausea in the past 24 hours was measured using a subjective Likert-type scale ranging from 1–4. Emesis was measured by nurses. Use of rescue medication was measured from nurse reports. Patients who withdrew from the study were considered nonresponders. Patient age, gender, alcohol consumption, emetic regimen, and duration of chemotherapy were evaluated as predictive of chemotherapy-induced nausea and vomiting (CINV). Odds ratios, Fisher’s exact test, a chi-squared test, and the Mann-Whitney U test were used.

The average number of days of chemotherapy was 4.7 with a range of 2–6 days in the historical cohort and 4.3 days with a range of 2–6 days in the palonosetron group. Complete control was 50% for overall, 58% for early, and 82% for the historical group. In the palonosetron group, the complete control was 81%, 84.5%, and 96.5%. Overall difference for the overall study period showed a p value of 0.001. The early period showed a p value of 0.002, and the p value of the late period was 0.022. In both cohorts, patients without nausea or with mild nausea did not experience emesis. Patients with emesis were significantly more prevalent in the ondansetron arm (p < 0.005).

The change to every other day palonosetron significantly improved the management of CINV in multiday high-dose chemotherapy.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)

Evidence supports every other day palonosetron, which is safe and effective for managing CINV in high-dose chemotherapy that is given over several days.

RESOURCE TYPE: Evidence-based guideline

• Not reported

• Basic oral care will reduce severity of oral mucositis and associated pain.
• An opioid-based systemic pain control program is usually needed.
• Topical coating agents and anesthetics may reduce mucosal sensitivity, but with short duration.
• Topical capsaicin should not be used.
• A transmucosal opioid is a rational approach to odynophagia, which should be viewed as incidental breakthrough pain.

No quality rating of evidence used is discussed, and numerous consensus statements are not supported by evidence or any references.

This guideline is a mix of consensus-based and evidence-based recommendations. Nurses should be aware of the need for patients to continue trying to swallow to avoid disuse muscle atrophy and fibrosis from treatment. This guideline suggests that pain on swallowing be managed as breakthrough pain, and that transmucosal opioids would be an appropriate approach for management.

To investigate the neural correlates of semantic strategic training in patients with distinct prefrontal cortex lesions

In the 30-minute semantic organizational strategy training, subjects were taught three steps to improve memory: (1) organize words into categories, (2) memorize words, and (3) retrieve words by category. Subjects were required to undergo a minimum of five training trials and to demonstrate that they had learned how to apply the semantic organizational strategy. Pre- and post-test evaluations consisted of subjects undergoing functional magnetic resonance imaging (fMRI) scanning immediately prior to and after the semantic strategy training.

• N = 21      
• MEAN AGE = 45.7 years for bilateral orbitofrontal cortex (BOFC) patients and 39.57 years for dorsolateral prefrontal cortex (LPFC) patients
• MALES: 57%, FEMALES: 43%
• KEY DISEASE CHARACTERISTICS: 21 patients with confirmed primary brain tumor (PBT) located in the prefrontal cortex, specifically the LPFC or BOFC
• OTHER KEY SAMPLE CHARACTERISTICS: At least six months post-chemotherapy and radiation therapy; time since surgical resection ranged from 6 months to 10 years (mean = 2.65 years; SD = 2.4 years); all subjects were non-aphasic, right-handed, and free of other neurological or psychiatric conditions.

• SITE: Not stated/unknown  
• SETTING TYPE: Not specified    
• LOCATION: Not stated but ethics approval was received from the University of Sao Paulo Medical School.

Exploratory study using a pre- and post-test design in a convenience sample

• 3 word lists of 16 words each: unrelated and related non-structures, and related structure word lists for cortical activation during scanning
• fMRI scan

Both subject groups recalled more words (p < 0.001) and organized more words together (p < 0.001) after semantic training. For the BOFC group, there were significant differences (p < 0.01) after the intervention of increased activation: (1) right cuneus and posterior cingulate gyrus, and left precuneus during the related structure word list trial and (2) left precentral gyrus, postcentral gyrus, inferior frontal gyrus, and insula during the unrelated word list trial. For the LPFC group, there were significant differences (p < 0.01) after the intervention, in multiple cortical areas: (1) increased activation in the left inferior frontal gyrus, precentral gyrus, and insula during the related non-structured word list trial (2) increased activation in the left inferior frontal gyrus, precentral gyrus, and anterior cingulate during the related structure word list trial, and (3) decreased activation in the left supramarginal gyrus, precuneus, superior temporal gyrus, and superior parietal lobe during the related structure word list.

The intervention increased use of categorizing words, thereby improving memory performance in subjects with prefrontal PBT. Changes in cortical activation suggest intervention application and recruitment of compensatory brain mechanisms for memory tasks. Further study with longitudinal measures is warranted to demonstrate continued cortical activation and intervention application during memory tasks.

• Small sample (< 30)
• Risk of bias (no control group)
• Findings not generalizable
• Intervention expensive, impractical, or training needs
• Other limitations/explanation: fMRI scanning for pre- and post-measures is expensive, is impractical, and requires specialized training and equipment. This study was performed in a homogenous sample.

This study demonstrated the application of a quick single session semantic training intervention aimed at improving verbal memory performance in those with known neuropathology.

The purpose of the study was to evaluate a protocol change of not routinely prescribing G-CSF to manage uncomplicated neutropenia in patients with Hodgkin lymphoma on adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) therapy.

Eligible patients who consented to participate had baseline data collected (demographics, comorbidities, standard blood tests, routing staging via computed tomography scan, and bone marrow biopsies when indicated, and prognostic factors). Response rates were evaluated via repeat computed tomography scans following completion of ABVD therapy. Patients with limited stage disease received 2–4 cycles of ABVD with involved field radiation and those with advanced stage disease received 6–8 cycles of ABVD. Blood tests were taken every two weeks. No primary prophylactic G-CSF was administered; but was given as secondary prophylactic for febrile neutropenia. Adjustments were made to the chemotherapy regimen for nonhematologic toxicities (peripheral neuropathy or lung toxicity). Comparisons were made to a retrospective chart review in which C-GSF was administered as primary prophylaxis.

• 33 in the prospective group, 89 in the retrospective study group
• Mean age was 38 years in the prospective group and 42 years in the retrospective group.
• 18 males (55%) were in the prospective group and 50 (56%) were in the retrospective group. 15 females (45%) were in the prospective group and 39 (46%) were in the retrospective group
• Key disease characteristics include biopsy-proven Hodgkin lymphoma
• Participants were excluded if neutropenic or if they had significant cytopenias prior to starting chemotherapy, Hodgkin lymphoma-related bone marrow involvement, initiating chemotherapy as an inpatient, and/or comorbidities of HIV, active infection, or severe cardiac or pulmonary disease

A single-site outpatient location (the London Regional Cancer Program)

Active antitumor treatment

Prospective cohort with comparison to historical cohort

• Statistical analyses included using two-tailed Mann-Whitney U test for continuous variable comparisons with chi-square or Fisher’s exact test for proportional comparisons.
• Taylor series approximation was used to calculate the absolute difference in risk of developing febrile neutropenia.
• Cost analysis was also conducted.

Six percent of patients in the prospective group (did not receive primary prophylactic G-CSF) acquired febrile neutropenia, interfering with 0.6% of chemotherapy treatments. There was no significant difference from the retrospective comparison group in rate of febrile neutropenia, although the prospective group had a significantly higher rate of neutropenia (p < 0.001). The cost savings to the institution of not using primary prophylactic G-CSF was $10,241.

Not using G-CSF as a primary prophylactic treatment for patients with uncomplicated neutropenia who are being treated with ABVD for Hodgkin lymphoma is safe and cost saving.

• Small sample (less than 100 participants)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)

Closely monitoring patients for febrile neutropenia would be highly important in patients not receiving G-CSF as primary prophylaxis. Educating patients and healthcare providers about the safety of not using G-CSF as a primary prophylactic treatment is important. While this study provides some evidence that primary prophylaxis may not be of benefit related to development of febrile neutropenia, the ability to draw firm conclusions is limited by study design and other limitations. Ongoing research in the most cost effective way to prevent infection is needed.

To focus on the role of psychostimulants, particularly methylphenidate, in the treatment of cancer-related fatigue (CRF).

Databases searched were MEDLINE, EMBASE, CINAHL, and Cochrane Register from inception to 2009.

Search keywords were not stated but appeared to be related to cancer-related fatigue and psychostimulants. According to the authors, “An exhaustive list of search terms was used and a systematic review methodology was applied.”

Studies were included if they were randomized, controlled trials testing a psychostimulant against a placebo or usual care in the treatment of CRF.

No exclusion criteria were stated.
 

The total number of references retrieved was not stated. One author screened relevant titles and abstracts. The final list of included studies was agreed on by all the authors. Data were “extracted and independently reviewed using predesigned data extraction forms. Data were entered into Cochrane review manager software.” More information on search terms and numbers of articles initially reviewed would have been helpful; it was unclear as to who designed the “predesigned data extraction forms.”

• The final number of studies included was five.
• The sample range across studies was 50 to 152 patients (N = 426 patients).
• Minimal information was provided.
• Mean age ranged from 50 to 71 years for the various studies (no range was provided).
• There appeared to be various tumor types and treatment both current and past.
• No other demographic data were provided.
   

• Patients were undergoing the transitional phase of care after initial treatment.
• The study has clinical applicability for late effects and survivorship and palliative care.

Four studies measured CRF with the Functional Assessment of Cancer Therapy–Fatigue (FACT-F), and one used the Brief Fatigue Inventory (BFI). There was a significant effect of psychostimulants over placebo (standardized mean difference = –0.28; 95% confidence interval [CI] [–0.48, –0.09]; p = 0.005). There was no difference in the rate of adverse effects between the drug and the placebo.

According to the authors, “evidence suggests that methylphenidate may be effective in management of CRF”; however, there was no large well-conducted clinical trial, and evidence from smaller trials was somewhat contradictory; thus, the authors stated “this advice must be considered to be tentative and provisional.”

Generally, this was a weak systematic review because the authors talked about performing an extensive search but provided no details about that search. The meta-analysis was also weak because only one (the largest) of the five studies showed improvement with psychostimulants compared to placebo.

Because there was no evidence about the long-term side effects of the medications, methylphenidate may best be used in patients with advanced disease or short-term use in those on active treatment. However, there was a trend toward benefit in some patients, and it may be worth a trial in selected patients as suggested by the authors.

To examine the role of methylphenidate and other drugs in the management of cancer-related fatigue

DATABASES: Cochrane Register of Controlled Trials, EMBASE, and hand searching of several journals and reference lists

KEYWORDS: neoplasms or cancer or carcinoma or tumour, bone marrow transplant, neutropenia, radiotherapy, fatigue. Complete listing of search terms is provided.

INCLUSION CRITERIA:

• Randomized controlled trial
• Designed to test a drug against placebo or usual care
• Use of a multi-item measure of fatigue

EXCLUSION CRITERIA:

• Measure of fatigue with single-item tool or visual analog scale

TOTAL REFERENCES RETRIEVED: Initial searching provided 5,841 articles and abstracts for screening. One hundred sixteen were reviewed in detail.

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Studies were done from 1992–2007. Data were collected from studies on a standard form by two independent reviewers, and any differences were resolved by consensus.

FINAL NUMBER STUDIES INCLUDED = 27

SAMPLE RANGE ACROSS STUDIES = 12–939

TOTAL PATIENTS INCLUDED IN REVIEW: 6,568 

KEY SAMPLE CHARACTERISTICS: Samples included a variety of tumor types, a variety of treatments, and patients in active treatment as well as after treatment.

Erythropoietin

Ten trials were included in meta-analysis.

• Dosages ranged from 3,000–40,000 units, and frequency varied.
• After 12 weeks of treatment, there was a significant reduction of fatigue (Z = 8.32, p <.001, SMD = -.038).
• Most patients were anemic.
• Half of the studies were open label.

Darbepoetin

Four trials were included in meta-analysis.

• After 12 weeks of treatment, there was a significant effect compared with placebo (Z = 1.96, p = .05, SMD = -0.13).
• All patients were anemic.

Paroxetine

Two studies were included.

• After eight weeks of treatment, there was no fatigue benefit (Z = 1.06, p = -.29, SMD = -0.08).

Progestational Steroids

Four studies were included—three with megestrol acetate and one with medroxyprogesterone acetate.

• After an average of eight weeks of treatment, no benefit was seen (Z = 1.06, p = .29, SMD = -0.18).
• There was substantial heterogeneity among trials.
• There was a consistent negative effect across all trials.

Methylphenidate

Two studies were included.

• There was no overall benefit (Z = 0.63, p = .53).

Single studies

• One study on 12 patients reported a significant effect of etanercept, an inhibitor of tumor necrosis factor.
• One study on 466 women with metastatic breast cancer reported a significant effect of ibandronate compared with placebo.

Findings suggest that there is no overall, effective pharmacologic management of cancer-related fatigue. Meta-analysis of progestational steroids report an overall negative effect, suggesting that this approach is counterproductive for fatigue management.

• There is some expected bias in results due to lack of complete study data in some trials.
• Overall effect sizes reported are small, so, though statistically significant, the actual effectiveness in the patient experience is unclear.

The majority of patients who were treated with hematopoietic growth factors were anemic, pointing to the need to correct anemia, rather than any direct effect on the symptom of fatigue. These results point to the need to clinically evaluate such potential causes of fatigue. Even in these cases, the effect size is relatively small.

To evaluate the effectiveness of pharmacologic interventions used for fatigue in patients with cancer

Databases searched were PaPaS, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, Dissertation Abstracts International (DAI), metaRegister of Controlled Trials (mRCT) (January 2007–October 2009). Journals searched were British Journal of Cancer, Journal of Clinical Oncology, Journal of Pain and Symptom Management, and Journal of Palliative Medicine. The reference lists of all articles were checked for additional studies. Conference abstracts also were searched.

Search keywords were neoplasms, bone marrow transplantation, cancer, carcinoma, tumour, adenocarcinoma, leukemia, lymphoma, malignant, radiotherapy, fatigue, tired, weary, weariness, exhausted, lack or loss or lost energy or vigor, apathy or lassitude or lethargy, or feeling drained, sleepy, or sluggish.

Studies were included in the review if they

• Assessed drug therapy for the management of cancer-related fatigue (CRF) compared to placebo, usual care, or a nonpharmacologic intervention.
• Were randomized, controlled trials (single-blind and open-label were allowed).
• Included adult patients with a clinical diagnosis of cancer.

This review was an update of a previous review. The updated search retrieved 647 additional references. Of those, six additional studies met the inclusion criteria. The final sample of studies included was 31.

The review included 7,104 participants who received a drug intervention for CRF.

Psychostimulants

• Four trials examined methylphenidate, and one used dexamphetamine. These included 426 patients total.
• Evidence existed of a significant effect on fatigue with methylphenidate over placebo, and evidence supported the use of psychostimulants in the treatment of CRF.
• The standardized mean difference was positive, with a small effect and narrow confidence interval (CI) (total mean difference = –0.28; 95% CI [-0.48, -0.09]; Z = 2.83; p = 0.005).
• Fatigue was measured with the Functional Assessment of Cancer Therapy-Fatigue (FACT-F) in all studies.

Erythropoietin and Darbepoetin

• Eleven studies were combined in total and demonstrated a positive effect. The weighted mean difference of studies using the FACT-F outcome measure in erythropoietin gave a score of 4.33, which was a clinically significant difference. The conclusion was limited to patients with anemia who were undergoing chemotherapy. Greater improvement was more likely in those with lower hemoglobin levels.
• In placebo-controlled trials of darbepoetin, the mean difference using the FACT-F score was -1.96, which was less than the minimally clinical significant difference.
• Combined analysis for both agents gave a mean difference score of 3.75, which was clinically significant. 
• Erythropoietin and darbepoetin cannot be recommended because of adverse events associated with these drugs.

Antidepressants/Paroxetine

• Two studies using paroxetine and a trial using sertraline were analyzed. Analysis showed no benefit for the treatment of CRF.

Progestational Steroids

• In studies that could be combined, no evidence existed to support continued use for the treatment of fatigue.
• The clinical significance of results of ibandronate were unclear.
• One study of etanercept during chemotherapy had statistically significant results, but the study had a small sample size and poor design. It was suggested that additional trials be conducted.
• One study of donepezil showed no benefit over placebo.

Four trials of methylphenidate provided evidence for use that was supportive but associated with a small effect size in a dose of 10–20 mg per day. Serious adverse events were minimal; however, clinicians need to review contraindications before prescribing. Additional large-scale trials were suggested using methylphenidate to further evaluate use in CRF. Erythropoietin and darbepoetin can no longer be recommended for CRF because of increased adverse events associated with these drugs. No current evidence exists to support the use of steroids.

• Reviewers found major limitations in the reporting of trials and multiple methods of measuring outcomes.
• Some outcomes in trials were not reported due to extensive missing data.
• These findings point to the need for improved research reporting to meet Consolidated Standards of Reporting Trials (CONSORT) guidelines and the benefit that could be derived from use of consistent methods of measuring outcomes.