Phase II, randomised, double-blind, placebo-controlled trial of methylphenidate for reduction of fatigue levels in patients with prostate cancer receiving LHRH-agonist therapy

Abstract

Objectives: To investigate whether methylphenidate can alleviate fatigue, as measured by the Functional Assessment of Cancer Therapy: Fatigue subscale, in men with prostate cancer (PCa) treated with a luteinizing hormone-releasing hormone (LHRH) for a minimum of 6 months, and to assess changes in global fatigue and quality of life (QoL) as measured by the Bruera Global Fatigue Severity Scale (BFS) and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), respectively.

Participants and methods: We performed a single-centre, randomised, double-blind, placebo-controlled trial with the aim of recruiting 128 participants. Men treated with a LHRH agonist for PCa were screened between February 2008 and June 2012 for fatigue at our outpatient clinics using the BFS. Participants were randomised to receive either 10 mg daily of methylphenidate or placebo. Change in fatigue levels and in SF-36 scores between both groups were compared using linear regression, adjusted for baseline scores.

Results: The study was closed prematurely because of poor accrual. Of the 790 subjects screened, 24 men were randomised to methylphenidate or placebo (12 per group). After 10 weeks, the improvement in mean [sd] fatigue score was greater in the methylphenidate than in the placebo arm (+7.7 [7.7] vs +1.4 [7.6]; P = 0.022). The within-group analysis showed a significant improvement in fatigue scores in the methylphenidate arm (P = 0.008) but not in the placebo arm (P = 0.82). The use of methylphenidate also resulted in a significantly greater improvement in QoL as measured by the physical and mental component summary scores than did the use of placebo (P = 0.04 for both component scores).

Conclusions: Our findings support the beneficial effect of methylphenidate on fatigue and QoL among men with LHRH-induced fatigue. Clinicians should be aware of these benefits and should consider discussing these findings with patients who have high levels of fatigue.

Keywords: androgen deprivation therapy; fatigue; gonadotropin-releasing hormone; methylphenidate; prostate cancer.