17 June 2024

Methylphenidate Versus Placebo for Treating Fatigue in Patients With Advanced Cancer: Randomized, Double-Blind, Multicenter, Placebo-Controlled Trial

(Journal of clinical oncology ;IF:45.3)

  • Stone PC, Minton O, Richardson A, Buckle P, Enayat ZE, Marston L, Freemantle N. Methylphenidate Versus Placebo for Treating Fatigue in Patients With Advanced Cancer: Randomized, Double-Blind, Multicenter, Placebo-Controlled Trial. J Clin Oncol. 2024 May 17:JCO2302639. doi: 10.1200/JCO.23.02639. Epub ahead of print. PMID: 38757263.

  • CORRESPONDING AUTHOR :Patrick Charles Stone, MD, MA, MRCP; e-mail:

    Marie Curie Palliative Care Research Department, Division of Psychiatry, University College London (UCL), London, United Kingdom

Purpose 目的

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.



Methods 方法

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.

这是一项随机、双盲、安慰剂对照、多中心试验。符合条件的患者患有晚期不可治愈的癌症且疲劳评分大于3/10。主要排除标准包括高血压、精神疾病、心血管疾病、脑血管疾病、肾脏、肝脏或血液疾病、物质依赖和癫痫。患者被随机分配到哌甲酯或安慰剂组,比例为1:1,起始剂量为每天两次,每次5毫克。哌甲酯/安慰剂的剂量每周调节一次,持续6周,最大剂量为每天三次,每次20毫克。试验在10周时结束。主要结果是组间在6 ± 2周时慢性病治疗相关性疲乏功能评估量表(FACIT-F)评分的差异。次要结果包括不良反应、生活质量和情绪。


Results 结果

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; P = .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.

162名患者(73名男性;平均年龄65.8岁;标准差[SD] 10.3岁)被随机分配,3名患者被排除在分析之外。77名患者分配到安慰剂组(基线FACIT-F=22 [SD, 10]);82名患者分配到哌甲酯组(FACIT-F=20 [SD, 9])。经过6±2周后,哌甲酯组的FACIT-F评分比安慰剂组高1.97分(95% CI,-0.95至4.90;P=0.186)。在整个10周的研究期间,哌甲酯组的FACIT-F评分名义上高于安慰剂组(差异,2.20 [95% CI,0.39至4.01]),但未达到临床上重要的差异(5分)。在6周时,除了抑郁评分在哌甲酯组名义上降低(差异,-1.35 [95% CI,-2.41至-0.30])外,两组在生活质量或症状领域没有差异。两组在死亡率或严重不良事件方面没有差异。


Conclusion 结论

After 6 ± 2 weeks of treatment, methylphenidate was not superior to placebo for treating fatigue in advanced cancer. Methylphenidate was safe and well-tolerated.

经过6 ± 2周的治疗,哌甲酯在治疗晚期癌症疲劳方面并不优于安慰剂。哌甲酯是安全且耐受性良好的。