A phase III, randomized placebo-controlled trial of the safety and efficacy of d-MPH as new treatment of fatigue and “chemobrain” in adult cancer patients

Background: This study investigated the safety and efficacy of dexmethylphenidate (d-MPH, Focalin) in the treatment of persistent fatigue and memory impairment after chemotherapy in non-anemic cancer patients. Methods: Adult patients (primary or metastatic brain tumors excluded) treated with ≥4 cycles of cytotoxic chemotherapy (completed ≥2 months prior to entry) were eligible. Patients completing a single-blind placebo period with no symptomatic improvement were randomized to an 8-week double-blind phase. Dosing (d-MPH or placebo) was adjusted from 10 to 50 mg/day and maintained for ≥2 weeks. Efficacy endpoints were change from Baseline (last observation carried forward) in the Functional Assessment of Chronic Illness Therapy-Fatigue Subscale (FACIT-F) Total Score (primary) and High Sensitivity Cognitive Screen (HSCS) Overall Total and Subscale Scores (secondary). Planned accrual was 160 to obtain 120 completed patients, based on comparison of FACIT-F scores in the 2 groups, assuming a 2-sided test with Type 1 error rate of 0.05, 80% power, mean FACIT-F scores of 36.8 (placebo) and 31.4 (d-MPH), and a common standard deviation of 10.5. Results: Overall, 152 patients (breast cancer: 76.0%; ovarian cancer: 13.6%) were randomized to placebo (n=75) or d-MPH (n=77); 132 patients completed. Significant improvement in the FACIT-F Total Score (Weeks 1, 5, 6, 7, 8; p<0.05) and HSCS Memory Subscale (Week 8; p<0.05) was observed in the d-MPH group versus placebo. Mean highest d-MPH dose was 27.7 mg/day. Common adverse events (AEs), headache (d

-MPH:

40.8%; placebo: 33.3%) and nausea (d

-MPH:

27.6%; placebo: 7.7%), were mostly mild to moderate. Serious AEs were reported in 2 subjects (placebo only). Conclusions: Dexmethylphenidate was well-tolerated and significantly more effective than placebo in improvement of fatigue and impaired memory after chemotherapy in adult cancer patients. For patients with fatigue and memory impairment after chemotherapy, dexmethylphenidate therapy should strongly be considered.