The results of the MePFAC study are likely to lead to changes in clinical practice and to the treatment recommendations contained in existing professional guidelines.
In the UK, the Palliative Care Formulary (PCF)42 is used as the reference text for prescribers in palliative medicine. The most recent edition of the formulary (PCF8) lists ‘fatigue refractory to correction of underlying contributory factors’ as one of the ‘beyond licence’ indications for MPH. However, the formulary notes that the use of psychostimulants for fatigue is controversial, and for this reason, use should be ‘reserved for fatigue refractory to other measures’. The National Comprehensive Cancer Network guidelines recommend that MPH may be considered for use in patients on treatment, post treatment and at the end of life, although they state that the drug ‘should be used cautiously and should not be used until treatment- and disease-specific morbidities have been characterised or excluded’.43 The European Society of Medical Oncology guideline development committee on cancer-related fatigue was unable to reach consensus on the issue. Some panel members recommended that psychostimulants might be considered in selected patients but that their usefulness and safety should be re-evaluated after a short time, and others considered that these drugs could not be recommended.44 The American Society of Clinical Oncology guidelines45 concluded that ‘evidence suggests that psychostimulants (e.g. MPH) and other wakefulness agents (e.g. modafinil) can be effectively used to manage fatigue in patients with advanced disease or those receiving active treatment. However, there is limited evidence of their effectiveness in reducing fatigue in patients after active treatment who are currently disease free’. On the basis of our research, MPH should no longer be recommended as a treatment for fatigue in patients with advanced cancer (even in selected cases or as a therapeutic trial for a short time period). The balance of the evidence now indicates that, even if MPH were to result in small improvements in fatigue (over and above those provided by placebo), the magnitude of such improvements is likely to be less than the MCID. There is stronger evidence for other management approaches (such as exercise), and further research in this area should focus on determining the optimum strategies for delivering such interventions and/or on the evaluation of other pharmacological and non-pharmacological approaches.
The results of our study have already been presented at the European Association of Palliative Care 13th World Research Congress (see Report Supplementary Material 7), and the main results have been published in a peer-reviewed journal.1 Members of the research team plan to work with national and professional associations to ensure that the findings are incorporated into updated guidelines. One of the co-applicants is working on an updated systematic review and meta-analysis of RCTs which will include the data from the MePFAC trial.