Marie Curie Palliative Care Research Department, Division of Psychiatry, University College London (UCL), London, United Kingdom.
University Hospitals Sussex NHS Foundation Trust, Worthing Hospital, Lyndhurst Road, Worthing, West Sussex, United Kingdom.
J Clin Oncol. 2024 Jul 10;42(20):2382-2392. doi: 10.1200/JCO.23.02639. Epub 2024 May 17.
To compare effects and side effects of 6 weeks of individually dose-titrated methylphenidate or placebo on fatigue in palliative care patients with advanced cancer.
This is a randomized, double-blind, placebo-controlled, multicenter trial. Eligible patients had advanced incurable cancer and fatigue >3/10. Principal exclusions were hypertension; psychiatric, cardiovascular, cerebrovascular, renal, liver, or blood disorders; substance dependency; and epilepsy. Patients were randomly assigned 1:1 methylphenidate or placebo starting at 5 mg twice daily. Dose of methylphenidate/placebo was titrated once per week, over 6 weeks, up to a maximum of 20 mg three times daily. Trial ended at 10 weeks. Primary outcome was the difference in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) scores between groups at 6 ± 2 weeks. Secondary outcomes included adverse effects, quality of life, and mood.
One hundred sixty-two patients (73 men; mean, 65.8; standard deviation [SD], 10.3 years) were randomly assigned, and three were excluded from analysis. Seventy-seven were allocated placebo (baseline FACIT-F = 22 [SD, 10]); 82 were allocated methylphenidate (FACIT-F = 20 [SD, 9]). After 6 ± 2 weeks, FACIT-F scores were 1.97 points (95% CI, -0.95 to 4.90; = .186) higher (better) on methylphenidate than placebo. Across 10 weeks of the study, FACIT-F was nominally higher in the methylphenidate group versus placebo (Diff, 2.20 [95% CI, 0.39 to 4.01]), but this did not reach the minimally clinically important difference (5-points). At 6 weeks, there were no differences between groups in quality-of-life or symptom domains except for depression scores (nominally reduced in the methylphenidate group: Diff, -1.35 [95% CI, -2.41 to -0.30]). There were no differences in mortality or serious adverse events.
After 6 ± 2 weeks of treatment, methylphenidate was not superior to placebo for treating fatigue in advanced cancer. Methylphenidate was safe and well-tolerated.
比较 6 周个体化滴定剂量哌醋甲酯与安慰剂对晚期癌症姑息治疗患者疲劳的影响和副作用。
这是一项随机、双盲、安慰剂对照、多中心试验。合格患者患有晚期不可治愈的癌症，且疲劳评分>3/10。主要排除标准为高血压；精神、心血管、脑血管、肾脏、肝脏或血液疾病；物质依赖；和癫痫。患者以 1:1 的比例随机分配哌醋甲酯或安慰剂，起始剂量为每日两次，每次 5mg。哌醋甲酯/安慰剂的剂量每周调整一次，6 周内最高剂量增至每日三次，每次 20mg。试验在 10 周时结束。主要结局是治疗 6±2 周时两组间功能性评估慢性疾病治疗疲劳量表（FACIT-F）评分的差异。次要结局包括不良反应、生活质量和情绪。
162 名患者（73 名男性；平均年龄 65.8[标准差 10.3]岁）被随机分配，其中 3 名患者被排除在分析之外。77 名患者分配安慰剂（基线 FACIT-F=22[标准差 10]）；82 名患者分配哌醋甲酯（FACIT-F=20[标准差 9]）。治疗 6±2 周后，哌醋甲酯组 FACIT-F 评分比安慰剂组高 1.97 分（95%置信区间，-0.95 至 4.90；=.186）。在研究的 10 周内，哌醋甲酯组的 FACIT-F 评分名义上高于安慰剂组（差异 2.20[95%置信区间，0.39 至 4.01]），但未达到最小临床重要差异（5 分）。在 6 周时，除抑郁评分外（哌醋甲酯组名义上降低：差异 -1.35[95%置信区间，-2.41 至 -0.30]），两组在生活质量或症状领域均无差异。死亡率或严重不良事件无差异。
在治疗 6±2 周后，哌醋甲酯治疗晚期癌症患者疲劳的效果并不优于安慰剂。哌醋甲酯安全且耐受良好。
