Richard, P.O., Fleshner, N.E., Bhatt, J.R., Hersey, K.M., Chahin, R., & Alibhai, S.M. (2014). A phase II, randomized, double-blind, placebo-controlled trial of methylphenidate for reduction of fatigue in prostate cancer patients receiving LHRH-agonist therapy. BJU International. Advance online publication. 

To determine if a 10-week regimen of methylphenidate could alleviate fatigue and improve quality of life in men with prostate cancer being treated with luteinizing hormone-releasing hormone agonists

Subjects were randomized to receive either methylphenidate or a placebo for up to 12 weeks. Methylphenidate was given at a dose of 5 mg daily for two weeks followed by 5 mg twice daily for eight weeks. The dose was tapered back to 5 mg per day for the last two weeks. Patients were contacted by phone at week 2 for reminders to take the medication and to assess drug tolerance. Assessments were done when patients were seen in-clinic at weeks 6, 10, and 12.

• N = 24  
• MEDIAN AGE = 66 years
• MALES: 100%   
• KEY DISEASE CHARACTERISTICS: All patients had prostate cancer.
• OTHER KEY SAMPLE CHARACTERISTICS: Baseline assessments suggested a moderate level of fatigue. Significantly more patients in the placebo arm had prior radical prostatectomy.

• SITE: Single-site    
• SETTING TYPE: Outpatient    
• LOCATION: Canada

• PHASE OF CARE: Active antitumor treatment

Double-blind, placebo-controlled, randomized trial

• Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) Scale
• Bruera Global Fatigue Severity Scale (BFS)
• Short-Form (36) Health Survey (SF-36)
• The National Cancer Institute's (NCI's) Common Terminology Criteria for Adverse Events (CTCAE)

FACIT scores improved significantly over the course of the study in all patients, but improvement was only statistically significant in the methylphenidate group (p = .008). The between-group difference in improvement was significant (p = .02). BFS scores also showed improvement in the methylphenidate group over time (p = .0006) but differences between study groups were not statistically significant. One patient discontinued the medication due to side effects.

Methylphenidate was shown in this small study to improve fatigue scores.

• Small sample (< 30)
• Measurement/methods not well described
• Measurement validity/reliability questionable
• Other limitations/explanation: There was difficulty in accruing subjects. Accrual was done over four years, and out of 345 eligible men, only 26 were recruited. This raises the question of the practicality and acceptability of this treatment to this group of patients. The Bruera scale is not commonly used, and no full description or reliability information is provided. The study was clearly underpowered.

Methylphenidate may be helpful to some patients in managing fatigue during cancer treatment. Due mostly to sample size limitations, this study does not provide strong evidence for use of methylphenidate in men with prostate cancer.