A systematic review on the role of fish oil for the treatment of cachexia in advanced cancer: an EPCRC cachexia guidelines project.

BACKGROUND: The European Palliative Care Research Collaboration is developing clinical guidelines on cachexia in patients with advanced cancer. A systematic review on the use of fish oil/omega-3-fatty acids (n-3-FA)/eicosapentaenoic acids (EPA) in advanced cancer patients suffering from cancer cachexia was performed as part of the guideline development. METHODS: The systematic literature search in Medline on the use of fish oil/n-3-FA/EPA identified 244 papers, with 38 publications included in the final evaluation. Some smaller trials, often unrandomized and without a control group, reported a good effect of n-3-FA in patients with advanced cancer and cachexia. However, the results of the larger randomized controlled trials could not support the positive results, as they mostly did not find a significant effect. RESULTS: Adverse effects such as abdominal discomfort, fish belching, fish aftertaste, nausea and diarrhoea were reported with a low incidence. No serious adverse effects were documented, but adverse effects often had an impact on quality of life. This often limited dose escalations or even led to discontinuation of n-3-FA. CONCLUSION: There is not enough evidence to support a net benefit of n-3-FA in cachexia in advanced cancer. On the other hand, adverse effects were infrequent, with no severe adverse effects. The results from the review led to a weak negative GRADE recommendation.

Patient-focused endpoints in advanced cancer: criterion-based validation of accelerometer-based activity monitoring.

BACKGROUND & AIMS: Objective assessment of daily physical activity (PA) by body-worn accelerometers offers potential as a novel endpoint in the clinical management of advanced cancer patients. This study aimed to assess criterion-based validity of an accelerometer-based activity monitoring system (AM-system), ActivPAL™, using two different methods. METHODS: Advanced cancer in patients and outpatients (Karnofsky Performance Status (KPS) 40-100). ActivPAL™ measurements were validated against (i) observations and (ii) energy expenditure (EE) measured by 2-week doubly-labelled water (DLW) protocol. RESULTS: Absolute errors for mean time spent in different body positions (<0.1%) and number of transfers (0%) were low. Step count error was significantly higher in patients with KPS 40-60 (non-self caring) compared to KPS 70-100 (self-caring) (33 vs. 24%, p = 0.006). Post-hoc mathematical analysis demonstrated that absolute errors for the mean energy expenditure of activity (EEA) (1.4%) and mean total EE (0.4%) were low, but agreement was also low. CONCLUSIONS: AM-systems provide valid estimates of body positions and transfers, but not step count, especially in non-self caring patients. ActivPAL™ can derive estimates of EE but there is considerable variability in results, which is consistent, in part, with the inaccuracy in step count. Further studies are required to assess the validity of different endpoints derived from AM-systems in advanced cancer patients.

Systematic review of the role of alternative application routes for opioid treatment for moderate to severe cancer pain: an EPCRC opioid guidelines project.

The European Palliative Care Research Collaboration is updating the EAPC recommendations on opioids in cancer pain management. A systematic literature search on Medline on the use of alternative routes for opioid application identified 242 papers, with 72 publications included in the final evaluation. Two or more alternative routes of opioid application were compared in 18 papers with a total of 674 patients. The best evidence base was available for the subcutaneous route. A comparison of subcutaneous and intravenous routes found no differences, confirming both routes as feasible, effective and safe. Efficacy and safety of the rectal route was comparable to the parenteral route. The side effect profile seemed to be very similar for the subcutaneous, intravenous, rectal or transdermal routes. Local side effects were reported for rectal application as well as for subcutaneous and transdermal administration. In conclusion, the systematic review found good evidence that subcutaneous administration of morphine or other opioids is an effective alternative for cancer patients if oral treatment is not possible. However, for a number of patients intravenous, rectal or transdermal therapy will offer a good alternative to the subcutaneous route. The review found no significant differences in efficacy or side effects between the alternative application routes.

Pharmacological treatments for fatigue associated with palliative care.

BACKGROUND: In healthy individuals, fatigue is a protective response to physical or mental stress, often relieved by rest. By contrast, in palliative care patients fatigue can be severely debilitating, thereby impacting daily activity and quality of life, often with rest not counteracting fatigue. Fatigue frequently occurs in patients with advanced disease and modalities treating cancer often contribute or cause fatigue. Further complicating issues are its multidimensionality, subjective nature, and lack of a consensus definition of fatigue. Pathophysiology is not fully understood and evidence-based treatment approaches are needed. OBJECTIVES: The objective was to determine efficacy of pharmacological treatments on non-specific fatigue in palliative care. The focus was on patients at an advanced stage of disease, including cancer and other chronic diseases associated with fatigue, aiming to relieve fatigue. Studies aiming at curative treatment (e.g. surgical intervention for early breast cancer) were not included. SEARCH STRATEGY: We searched EMBASE; Psych Lit, CENTRAL and MEDLINE to June 2009. SELECTION CRITERIA: We considered randomised controlled trials (RCTs) concerning adult palliative care with focus on pharmacological treatment of fatigue. The primary outcome had to be non-specific fatigue (or related terms such as asthenia). DATA COLLECTION AND ANALYSIS: Results were screened and included if they met the selection criteria. If two or more studies were identified that investigated a specific drug in a population with the same disease, meta-analysis was conducted. In addition, comparison of type of drug investigated in a specific population as well as comparison of frequent adverse effects of fatigue treatment was done by creating overview tables. MAIN RESULTS: More than 2000 publications were screened, and 22 met inclusion criteria. In total, data from 11 drugs and 1632 participants were analysed. Studies investigating amantadine, pemoline, and modafinil in participants with Multiple Sclerosis (MS)-associated fatigue and methylphenidate in patients suffering from advanced cancer and fatigue could be used for meta-analysis. Amantadine in MS and methylphenidate in cancer patients showed a superior effect. Most studies had low participant numbers and were heterogenous. AUTHORS' CONCLUSIONS: Based on limited evidence, we cannot recommend a specific drug for treatment of fatigue in palliative care patients. Surprisingly, corticosteroids have not been a research focus for fatigue treatment, although these drugs are frequently used. Recent fatigue research seems to focus on modafinil, which may be beneficial although there is no evidence currently. Amantadine and methylphenidate should be further examined. Consensus regarding fatigue assessment in advanced disease is needed.