Our research recommendations in priority order are, firstly, that a number of studies has now been undertaken to investigate the effectiveness or otherwise of MPH for the relief of fatigue in patients with advanced cancer, and the results of our study, combined with the balance of evidence from previous trials, suggests that further research to evaluate the effectiveness of this intervention, for this indication, in this population, is no longer warranted.
Secondly, although MPH was not effective at treating fatigue in advanced cancer, it was reasonably well-tolerated and safe to use. For that reason, it may still be reasonable to consider further trials to evaluate the effect of MPH on other symptoms of advanced cancer which are otherwise difficult to treat (e.g. opioid-induced drowsiness or low mood).
Finally, and notwithstanding the neutral results of our study (lack of effectiveness of MPH), cancer-related fatigue remains a significant problem for patients with advanced cancer, and improving the management of this symptom should remain a priority for research funders. There is a number of further plausible candidate pharmacological interventions that are in need of further evaluation in RCTs, including paroxetine,46 anamorelin (a selective ghrelin agonist)47 and ginseng.48 Exercise is probably the intervention with the best evidence for effectiveness for relief of fatigue,8,49 although further research is needed into the best way to deliver exercise to patients with advanced cancer and to understand the extent to which exercise should be used as part of a multimodal approach to fatigue management (combined with nutritional, psychological and pharmacological interventions).