晚期疾病状态的前列腺癌治疗心脏毒性图 (PROXMAP)：使用治疗史贝叶斯模型进行系统回顾和网络荟萃分析。
Prostate Cancer Therapy Cardiotoxicity Map (PROXMAP) for Advanced Disease States: A Systematic Review and Network Meta-analysis with Bayesian Modeling of Treatment Histories.
发表日期：2024 Sep 18
作者：
Moez Karim Aziz, Donald Molony, Dominique Monlezun, Travis Holder, Oliver Brunckhorst, Noel Higgason, Jerry Roland, Resa Magill, Mariya Fatakdawala, Alexander Iacobucci, Neal Mody-Bailey, Chris Owen, Andrew Zarker, Emma Thames, Justin Swaby, Daniel Xiao, Lily Choi, Shubh Desai, Jacob Galan, Brett Deng, Taylor Hartshorne, Alexis Nichols, Allan Zhang, Jared Imber, Jeffrey Song, William Jones, Alexis Rivas, Darren Sanchez, Maya Guhan, Giorgio Gandaglia, Shreyas Ranganath, Jerril Jacob, Skyler Howell, Juan Plana, Roderick van den Bergh, Matthew Roberts, Silke Gillessen Sommer, Jan Oldenburg, Guillaume Ploussard, Derya Tilki, Ivo Schoots, Erik Briers, Johan Stranne, Olivier Rouviere, Inge van Oort, Daniela Oprea-Lager, Maria De Santis, Philip Cornford,
来源：
EUROPEAN UROLOGY
摘要：
由于缺乏明确的既往证据，转移性激素敏感型（mHSPC）、非转移性去势抵抗性（M0CRPC）和转移性去势抵抗性（mCRPC）前列腺癌的一线治疗推荐并未考虑心脏毒性。本手稿评估了这些疗法的心脏毒性。我们检索了 Ovid Medline、Elsevier Embase 和 Cochrane 图书馆的随机临床试验 (RCT)，从数据库建立到 2024 年 1 月 14 日。一线 mHSPC、M0CRPC 和 mCRPC 的网络荟萃分析治疗方法是针对国际心脏肿瘤学会定义的五种心脏毒性指标构建的：心力衰竭、心肌炎、血管毒性、高血压和心律失常。其他贝叶斯网络荟萃分析还考虑了既往治疗史。纳入了 13 项随机对照试验（16 292 名患者）。对于 mHSPC，雄激素剥夺疗法 (ADT) 加多西紫杉醇 (DTX) 加醋酸阿比特龙 (AA) 加泼尼松 (P) 与 ADT 相比，高血压和心律失常显着增加（风险比 [RR] 2.85，95% 置信区间 [CI]） ] 1.67-4.89，RR 2.01，95% CI 1.17-3.44）；然而，ADT DTX 加达洛鲁胺 (DAR) 和 ADT DTX 之间没有观察到相应的差异（分别为 RR 1.55，95% CI 0.73-3.30 和 RR 0.94，95% CI 0.63-1.40）。对于假设有 mHSPC 治疗史的 mCRPC，ADT AA P 加奥拉帕尼 (OLA) 与 ADT AA P 相比，高血压显着降低（RR 0.20，95% CI 0.16-0.26）。 M0CRPC 结果并不显着。对于 mHSPC，ADT DTX DAR 表现出比 ADT DTX AA P 更低的心脏毒性，因为盐皮质激素过量减少导致高血压和心律失常的风险较低。此外，在先前 mHSPC 治疗雄激素剥夺后，OLA 与 ADT AA P 叠加用于 mCRPC 治疗时，与直觉相反，可降低高血压。版权所有 © 2024 欧洲泌尿外科协会。由 Elsevier B.V. 出版。保留所有权利。
Recommendations of first-line therapies for metastatic hormone-sensitive (mHSPC), nonmetastatic castrate-resistant (M0CRPC), and metastatic castrate-resistant (mCRPC) prostate cancer do not account for cardiotoxicity due to a lack of clear prior evidence. This manuscript assesses cardiotoxicity of these therapies.We searched Ovid Medline, Elsevier Embase, and the Cochrane Library for randomized clinical trials (RCTs) from database inception to January 14, 2024. Network meta-analyses of first-line mHSPC, M0CRPC, and mCRPC therapies were constructed for the five cardiotoxicity metrics defined by the International Cardio-Oncology Society: heart failure, myocarditis, vascular toxicity, hypertension, and arrhythmias. Additional Bayesian network meta-analyses also accounted for prior treatment history.Thirteen RCTs (16 292 patients) were included. For mHSPC, androgen deprivation therapy (ADT) plus docetaxel (DTX) plus abiraterone acetate (AA) with prednisone (P) demonstrated a significant increase in hypertension and arrhythmias versus ADT + DTX (risk ratio [RR] 2.85, 95% confidence interval [CI] 1.67-4.89, and RR 2.01, 95% CI 1.17-3.44, respectively); however, no corresponding differences were observed between ADT + DTX plus darolutamide (DAR) and ADT + DTX (RR 1.55, 95% CI 0.73-3.30, and RR 0.94, 95% CI 0.63-1.40, respectively). For mCRPC assuming a history of mHSPC treatment, ADT + AA + P plus olaparib (OLA) demonstrated a statistically significant decrease in hypertension versus ADT + AA + P (RR 0.20, 95% CI 0.16-0.26). M0CRPC results were unremarkable.For mHSPC, ADT + DTX + DAR demonstrates less cardiotoxicity than ADT + DTX + AA + P due to a lower risk of hypertension and arrhythmias from decreased mineralocorticoid excess. In addition, OLA counterintuitively offers decreased hypertension when superimposed on ADT + AA + P for mCRPC treatment after prior androgen deprivation from mHSPC therapy.Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.