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.
El cáncer y su tratamiento puede inducir a la evidencia objetiva y subjetiva de la disminución de la capacidad funcional que abarca la fatiga física y deterioro cognitivo. Dexmetilfenidato (D-MPH, el D-isómero del metilfenidato) fue evaluado para el tratamiento de la quimioterapia deterioro relacionado con la fatiga y el cognitivo. Un estudio aleatorizado, doble ciego, controlado con placebo, de grupos paralelos evaluó el posible efecto terapéutico y la seguridad de D-MPH en el tratamiento de pacientes con fatiga relacionada con la quimioterapia. Cambio desde el inicio de la Evaluación Funcional de Terapia de Enfermedades Crónicas-Fatiga Subescala (FACIT-F) La puntuación total en la semana 8 fue la medida de resultado primaria. Ciento cincuenta y cuatro pacientes (en su mayoría con tumores de mama y de ovario) fueron randomizados y tratados. Comparado con placebo, D-MPH-tratados con los sujetos demostraron una mejoría significativa en los síntomas de fatiga en la semana 8 en el FACIT-F (p = 0,02) y las clínicas de gravedad general de Impresión de las puntuaciones (p = 0,02), sin cambios clínicos relevantes en la hemoglobina los niveles. La función cognitiva no ha mejorado significativamente. Hubo una mayor tasa de estudio relacionados con las drogas acontecimientos adversos (AA) (48 de 76 [63%] versus 22 de 78 [28%]) y una tasa de abandono más alta debido a acontecimientos adversos (8 de 76 [11%] frente a . 1 de 78 [1,3%]) en D-MPH-temas tratados en comparación con los sujetos tratados con placebo. El AA más comúnmente informados independiente de la relación del fármaco del estudio en los tratados con D-MPH-sujetos fueron dolor de cabeza, náuseas y sequedad de boca, y en los sujetos tratados con placebo fueron cefalea, diarrea, insomnio y. D-MPH produjo una mejoría significativa de la fatiga en pacientes previamente tratados con quimioterapia citotóxica. Otros estudios con D-MPH u otros agentes para explorar la respuesta al tratamiento de la fatiga asociada a la quimioterapia debe ser considerada.
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.
Diseño del estudio»Ensayo controlado aleatorizado (ECA)
