Methylphenidate for Hematologic Cancer–Related Fatigue: A Randomized Clinical Trial

PURPOSE: Patients with hematologic cancer rate fatigue as their most frequent and severe unmet issue. Methylphenidate (MTP) has been reported to alleviate cancer-related fatigue (CRF) in some studies, but data from hematologic cancers are lacking. We investigated MTP for hematologic CRF. METHODS: Using a double-blinded, placebo-controlled, two-period, crossover design, 152 adult fatigued patients with hematologic cancer were randomly assigned to 6 weeks of either MTP or placebo, with a treatment-free week before the crossover. Eligibility required a Visual Analog Scale fatigue score ≥4 (range, 0-10), hemoglobin ≥8.0 g/dL, no chemotherapy within 8 weeks, and no concomitant psychopharmacologic treatment. The primary end point was the between-group difference in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) score from baseline to end of each period. RESULTS: The median age was 59.0 years (range, 21-83), 44% were women, the performance status was 0 in 57.3%, and 11% had received high-dose therapy. FACIT-F improved 8.9 points (95% CIs, 7.3 to 10.4) after MTP and 3.9 points (95% CI, 2.3 to 5.4) after placebo. The between-group difference of 5.0 points (95% CI, 2.8 to 7.2) was in favor of MTP. Reduced fatigue ratings in favor of MTP were also observed using other tools. Toxicity was mild, but more adverse events were reported during the MTP (N = 73; 57%) versus placebo (N = 52; 40%) periods. CONCLUSION: MTP treatment alleviated fatigue and may be considered as a pharmacologic fatigue intervention in patients with hematologic cancer.