Tombal Bertrand F, Freedland Stephen J, Armstrong Andrew J, Beer Tomasz M, Stenzl Arnulf, Sternberg Cora N, Hussain Maha, Ganguli Arijit, Ramaswamy Krishnan, Bhadauria Hemant, Ivanescu Cristina, Turnbull James, Holmstrom Stefan, Saad Fred
Urology, Cliniques universitaires Saint-Luc, UCLouvain, Brussels, Belgium.
Urology, Center for Integrated Research in Cancer and Lifestyle, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Prostate Cancer Prostatic Dis. 2022 Feb;25(2):288-295. doi: 10.1038/s41391-021-00447-9. Epub 2021 Sep 13.
Fatigue is a multifactorial symptom commonly reported by patients with prostate cancer as a result of disease and treatment. This study assesses the impact enzalutamide has on patient-reported fatigue ("fatigue") by using patient-reported outcomes from four pivotal, placebo-controlled trials of enzalutamide (ARCHES (NCT02677896), PROSPER (NCT02003924), PREVAIL (NCT01212991), and AFFIRM (NCT00974311)).
Fatigue was assessed in the individual studies using the Functional Assessment of Cancer Therapy-Prostate item GP1 at baseline, weeks 13 or 17, and every 12 weeks until disease progression. Longitudinal changes were assessed using mean scores and mixed-model repeated measures.
The fatigue rates at baseline were higher in patients with later-stage disease (metastatic and/or castration-resistant prostate cancer (CRPC)) and among patients who had already received prior treatment lines; rates ranged between 58% in PROSPER (nonmetastatic CRPC) and 86% in AFFIRM (post-docetaxel metastatic CRPC). Irrespective of disease state, initiation of enzalutamide or placebo resulted in an early increase of fatigue (by weeks 13 or 17), with fatigue levels stabilizing thereafter. At last assessment, ≥55% of patients reported fatigue improvement or stabilization in all trials compared to baseline. More patients reported fatigue worsening by ≥1 or ≥2 units with enzalutamide plus androgen deprivation therapy (ADT) than with placebo plus ADT in ARCHES, PROSPER, and PREVAIL, but the between-group difference was <10% in all trials.
The levels of fatigue were greater in mCRPC and lower in earlier states of disease. In all trials, patients reported a small increase in fatigue for the first 13-17 weeks after starting enzalutamide or placebo, with slightly greater fatigue with enzalutamide in all studies except AFFIRM, but fatigue stabilized or improved thereafter. This suggests a role for clinical management of fatigue to help patients cope early in treatment.
疲劳是前列腺癌患者因疾病和治疗而普遍报告的一种多因素症状。本研究通过使用恩杂鲁胺四项关键的、安慰剂对照试验（ARCHES（NCT02677896）、PROSPER（NCT02003924）、PREVAIL（NCT01212991）和AFFIRM（NCT00974311））的患者报告结局，评估恩杂鲁胺对患者报告的疲劳（“疲劳”）的影响。
在各单项研究中，使用癌症治疗功能评估-前列腺项目GP1在基线、第13或17周以及每12周直至疾病进展时评估疲劳情况。使用平均得分和混合模型重复测量来评估纵向变化。
晚期疾病（转移性和/或去势抵抗性前列腺癌（CRPC））患者以及已经接受过先前治疗线的患者在基线时的疲劳率较高；发生率在PROSPER（非转移性CRPC）中的58%至AFFIRM（多西他赛后转移性CRPC）中的86%之间。无论疾病状态如何，开始使用恩杂鲁胺或安慰剂都会导致疲劳早期增加（到第13或17周），此后疲劳水平稳定。在最后一次评估时，与基线相比，所有试验中≥55%的患者报告疲劳有所改善或稳定。在ARCHES、PROSPER和PREVAIL中，与安慰剂加雄激素剥夺治疗（ADT）相比，更多患者报告恩杂鲁胺加ADT导致疲劳恶化≥1或≥2个单位，但所有试验中组间差异均<10%。
mCRPC患者的疲劳水平较高，而疾病早期状态下的疲劳水平较低。在所有试验中，患者报告在开始使用恩杂鲁胺或安慰剂后的前13 - 17周疲劳略有增加，除AFFIRM外，所有研究中恩杂鲁胺导致的疲劳略多，但此后疲劳稳定或改善。这表明疲劳的临床管理有助于患者在治疗早期应对。
