Efficacy of Dexmethylphenidate for the Treatment of Fatigue After Cancer Chemotherapy: A Randomized Clinical Trial

Abstract Cancer and its treatment can induce subjective and objective evidence of diminished functional capacity encompassing physical fatigue and cognitive impairment. Dexmethylphenidate ( d -MPH; the d -isomer of methylphenidate) was evaluated for treatment of chemotherapy-related fatigue and cognitive impairment. A randomized, double-blind, placebo-controlled, parallel-group study evaluated the potential therapeutic effect and safety of d -MPH in the treatment of patients with chemotherapy-related fatigue. Change from baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue Subscale (FACIT-F) total score at Week 8 was the primary outcome measure. One hundred fifty-four patients (predominantly with breast and ovarian cancers) were randomized and treated. Compared with placebo, d -MPH-treated subjects demonstrated a significant improvement in fatigue symptoms at Week 8 in the FACIT-F ( P = 0.02) and the Clinical Global Impression-Severity scores ( P = 0.02), without clinically relevant changes in hemoglobin levels. Cognitive function was not significantly improved. There was a higher rate of study drug-related adverse events (AEs) (48 of 76 [63%] vs. 22 of 78 [28%]) and a higher discontinuation rate because of AEs (8 of 76 [11%] vs. 1 of 78 [1.3%]) in d -MPH-treated subjects compared with placebo-treated subjects. The most commonly reported AEs independent of study drug relationship in d -MPH-treated subjects were headache, nausea, and dry mouth, and in placebo-treated subjects were headache, diarrhea, and insomnia. d -MPH produced significant improvement in fatigue in subjects previously treated with cytotoxic chemotherapy. Further studies with d -MPH or other agents to explore treatment response in chemotherapy-associated fatigue should be considered.