Management of Fatigue in Patients with Advanced Cancer.

OPINION STATEMENT: Fatigue is a common and distressing symptom experienced by patients with cancer. It is most common in patients with locally advanced or metastatic incurable disease. It can have profound effects on quality-of-life and physical functioning. In addition to general supportive measures (directed at tackling contributory conditions and comorbidities), a variety of specific interventions have been developed which can be broadly categorised as physical therapies, psychological therapies or medication. There is some evidence that each of these approaches can have benefits in patients with earlier stage disease, those undergoing active treatment and in cancer survivors. The best evidence is for aerobic exercise, yoga, cognitive-behavioural therapy (CBT) and psycho-educational interventions. Less strong evidence supports the use of medications such as methylphenidate or ginseng. In patients with advanced disease, it is likely that the mechanisms of fatigue or the factors contributing to fatigue maintenance may be different. Relatively fewer studies have been undertaken in this group and the evidence is correspondingly weaker. The authors recommend the cautious use of aerobic exercise (e.g. walking) in those who are still mobile. The authors advise considering the use of psycho-educational approaches or CBT in those patients who are able to engage in such forms of therapy. In patients near the end-of-life, the authors advise use of dexamethasone (short-term use) and other pharmacological treatments only on the basis of a clinical trial.

Improved cancer-related fatigue in a randomised clinical trial: methylphenidate no better than placebo.

INTRODUCTION: Methylphenidate is a psychostimulant drug used to treat fatigue in patients with advanced cancer, for which there is no gold standard of treatment. OBJECTIVE: To explore the efficacy of methylphenidate in the relief of fatigue in patients with advanced cancer. MATERIALS AND METHODS: A randomised double-blind placebo-controlled multicentre clinical trial, stratified according to the intensity of fatigue. The treatment was considered effective if the improvement in mean fatigue intensity between baseline values and day 6 was significantly higher in the methylphenidate group than in the placebo group. The responses were measured using the Edmonton Symptoms Assessment System (ESAS) and the Functional Assessment of Cancer Therapy-Fatigue (FACT-F) scales. RESULTS: 35 patients received placebo and 42 patients received methylphenidate. The populations of both groups were homogeneous. Patients receiving methylphenidate did not exhibit statistically significant improvement of fatigue in comparison to patients receiving placebo (p=0.52). The mean improvement of fatigue (ESAS) on day 6 was -1.9 (±2.5) in the placebo group, and -2.3 (±2.6) in the methylphenidate group (p=0.52). The results obtained with the FACT-F were congruent with those obtained by the ESAS. The responses in patients with severe fatigue were -2.4 (±2.9) in the placebo group and -3.4 (±2.5) in the methylphenidate group; the difference was not statistically significant (p=0.3). CONCLUSION: Methylphenidate was not more efficient than placebo to treat cancer-related fatigue. Fatigue improved significantly after 3 days of treatment and was stabilised on day 6, both with placebo and methylphenidate. The side effects of methylphenidate were mild and infrequent. TRIAL REGISTRATION NUMBER: EudraCT Registry (2008-002171-27).

Placebo response in trials of drug treatments for cancer-related fatigue: a systematic review, meta-analysis and meta-regression.

BACKGROUND: Cancer-related fatigue (CRF) is one of the most distressing symptoms experienced by patients. There is no gold standard treatment, although multiple drugs have been tested with little evidence of efficacy. Randomised controlled trials (RCTs) of these drugs have commented on the existence or size of the placebo response (PR). The objective of this systematic review was to establish the magnitude of the PR in RCTs of drugs to relieve CRF and to identify contributing factors. METHOD: RCTs were included in which the objective was to treat CRF. A meta-analysis was conducted using the standardised mean change (SMC) between baseline and final measurement in the placebo group. To explore factors that may be associated with the PR (eg, population or drug), a meta-regression was undertaken. Risk of bias was assessed using the revised Cochrane tool. RESULTS: From 3916 citations, 30 relevant RCTs were identified. All had limitations that increased their risk of bias. The pooled SMC in reduction in fatigue status in placebo groups was -0.23 (95% confidence intervals -0.42 to -0.04). None of the variables analysed in the meta-regression were statistically significant related to PR. CONCLUSION: There is some evidence, based on trials with small samples, that the PR in trials testing drugs for CRF is non-trivial in size and statistically significant. We recommend that researchers planning drug studies in CRF should consider implementing alternative trial designs to better account for PR and decrease impact on the study results.

The use of methylphenidate to relieve fatigue.

PURPOSE OF REVIEW: To review recent evidence on the efficacy and safety of methylphenidate as a symptomatic treatment of patients with cancer-related fatigue (CRF). RECENT FINDINGS: Five clinical trials published since 2011 were identified. Two of these concluded that methylphenidate is more efficacious than placebo in providing relief from CRF, but the remaining three showed no difference in favour of methylphenidate. The studies were heterogeneous as per the dosage, scales used for evaluating fatigue and the target group studied. None of the studies detected serious reactions, and only mild and infrequent side-effects of methylphenidate were reported. Three new metanalyses show the slightly superior effect of methylphenidate compared to placebo in CRF. SUMMARY: Overall, literature supports the existence of moderate benefit of methylphenidate in CRF, backed up by weak evidence. Future studies should aim at better identifying the profile of patients who would benefit most from this pharmacological intervention.

Palliative Care Bedside Teaching: A Qualitative Analysis of Medical Students' Reflective Writings after Clinical Practices.

CONTEXT: A mandatory course in palliative care (PC) is organized for all final-year medical students at the University of Navarre. It consists of 24 lectures, 4 workshops, and 1 scheduled five hour clinical PC service experience at two different sites. In the 48 hours after the visit and related to the clinical experience, each student has to complete a 500-word reflective writing (RW) piece. OBJECTIVE: To investigate how a brief PC clinical experience helps equip the medical student. METHODS: Qualitative study of RW. Two researchers produced a content analysis of students' RW. They collaboratively developed themes and categories with a constant review of the classification tree and an exhaustive collection of quotes. Differences between services were analyzed (λ2). RESULTS: One hundred sixty-seven RW were analyzed from the 197 students on the course (response rate 85%). Six major themes emerged: All the students identified central aspects of PC work dynamics; students acquired specific PC knowledge (86%); the personal influence of the experience was reported (68%); students described how patients and their caregivers deal with the patients' illness (68%); students talked about the essence of PC and essential aspects of medicine (42%); students reported spontaneously having changed their assumptions about PC (15%); and they realized that the experience was relevant to all clinical practice. Categories such as teamwork, the expression of patients' and caregivers' feelings, and family devotion showed statistical differences between services (λ2 p < 0.05). CONCLUSION: A short bedside clinical experience in PC, encouraging student reflection, provides a deeper understanding of PC and even of core medicine values. The data we gather cannot explain only new skill acquisition but seems to suggest a life-changing personal experience for the student.