Moraska, A. R., Sood, A., Dakhil, S. R., Sloan, J. A., Barton, D., Atherton, P. J., . . . Loprinzi, C. L. (2010). Phase III, randomized, double-blind, placebo-controlled study of long-acting methylphenidate for cancer-related fatigue: North Central Cancer Treatment Group NCCTG-N05C7 trial. Journal of Clinical Oncology, 28, 3673–3679.
To evaluate the efficacy of long-acting methylphenidate in alleviating cancer-related fatigue (CRF), assess tolerability, and determine the effects on quality of life (QOL) in patients with CRF. Prior studies of methylphenidate have yielded mixed results. The drug used here was a mixture of d and l isomers of methylphenidate.
Patients were stratified according to disease stage, baseline fatigue scores, and whether they were receiving concomitant cancer treatment. They were then randomized to receive methylphenidate or placebo for four weeks. Patients took one tablet (18 mg of long-acting methylphenidate) on days 1 to 7, two tablets (36 mg) on days 8 to 14, and three tablets (54 mg) on days 15 to 28. Tablets were to be taken in the morning. A standard dose modification procedure was used in case of adverse effects attributed to the study drug.
The study was a double-blind, randomized, placebo-controlled trial.
In advanced stage disease (stage III–IV), mean improvement in fatigue was 19.7 with methylphenidate and 2.1 with placebo (p = 0.02) Early stage patients had less improvement with methylphenidate than those receiving placebo. Similar trends were seen in SF-36 measures; however, differences between groups were not statistically significant. Self-reported adverse events showed a significant increase in nervousness (p = 0.003) and appetite loss (p = 0.034) in the methylphenidate arm. Individuals in the placebo arm reported improvements in self-reported adverse effects in nervousness, shakiness, appetite loss, abdominal pain, and sex drive. Both study groups were similar in terms of gender distribution, age, disease stage, and other baseline measures.
The study demonstrated benefit for d-methylphenidate compared with placebo in alleviating CRF. Methylphenidate appeared to have some benefit in patients with advanced stage of disease.
There appeared to be some benefit of long-acting methylphenidate in patients with more advanced disease; however, these patients also experienced adverse effects. For use in these patients, benefits in terms of fatigue would need to be weighed against the adverse effects for individual patients from the patient's perspective.
The study findings suggest that further research on effectiveness, particularly in patients with more advanced disease, is warranted.