A randomized, double-blind, controlled trial of methylphenidate for fatigue in patients with advanced cancer.

TPS321 Background: Fatigue is the most common and one of the most distressing symptoms in patients with advanced cancer. Currently, there is no standard treatment for this multidimensional syndrome. Methylphenidate is found to be well-tolerated, with minimal side-effects, in both elderly and frail populations. Our objective through this ongoing trial is to determine the affect of methylphenidate on patients with fatigue, as well as investigate the role a nursing telephone intervention (NTI) plays in the improvement of fatigue. During an initial study, our group found that methylphenidate reduces opioid-induced sedation. More recent research by our group suggests that methylphenidate and a NTI are both capable of significantly reducing fatigue (Bruera et. al., JCO 2006). In order to better understand these preliminary results, we developed this clinical trial. Methods: Advanced cancer patients with fatigue ≥ 4/10 on the Edmonton Symptom Assessment Scale (ESAS), normal cognition evidenced by the Mini Mental State Examination (MMSE), no evidence of major depression and hemoglobin ≥ 8 are eligible. Following enrollment, patients are randomized twice. The first blinded randomization occurs to determine if eligible patients will receive methylphenidate or a placebo for their treatment of fatigue. The second randomization occurs to determine if patients will receive a NTI or not. This allows our group to isolate the affects both methylphenidate and a NTI play on improving patient fatigue. It also allows us to determine if there is a synergistic affect of receiving both methylphenidate and a NTI. The data will be analyzed in four groups: methylphenidate and a NTI, placebo and a NTI, methylphenidate and no specific phone call intervention (NSPCI) and finally, placebo and a NSPCI. The primary endpoint is fatigue, measured by the Functional Assessment of Chronic Illness–Fatigue (FACIT-F), administered at baseline and day 14. Following week 2, patients enter an open phase where all patients receive methylphenidate 5 mg every two hours, as needed, up to 20 mg/day through Day 36. The study blinding code will not be broken before entering this open phase. Total sample size is 250 patients; we have accrued 125 patients. No significant financial relationships to disclose.