鲁卡帕尼治疗卵巢癌：安全性、疗效及治疗地位的最新进展
Rucaparib in ovarian cancer: an update on safety, efficacy and place in therapy.
作者信息
Dal Molin Graziela Z, Omatsu Kohei, Sood Anil K, Coleman Robert L
机构信息
Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Gynecology, The Cancer Institute Hospital, Tokyo, Japan.
出版信息
Ther Adv Med Oncol. 2018 Jun 22;10:1758835918778483. doi: 10.1177/1758835918778483. eCollection 2018.
Abstract
Rucaparib is a poly (ADP-ribose) polymerase (PARP) inhibitor and potent inhibitor of PARP1, PARP2 and PARP3 enzymes. Phase II and III trials have documented that rucaparib has single-agent antitumor activity in patients with high-grade ovarian carcinoma, with both -mutated (germline and somatic) and with homologous recombination deficiency (HRD). Rucaparib as a maintenance treatment showed increased progression-free survival in patients with ovarian carcinoma who achieved a response to platinum-based chemotherapy, with an acceptable safety profile. The approval of this drug, along with the companion diagnostic FoundationFocus CDxBRCA test represents an important new therapeutic option in the treatment of ovarian cancer. This article reviews the mechanisms of action, safety, pharmacokinetics and pharmacodynamics and indications for use of rucaparib as well as future trials.
摘要
鲁卡帕尼是一种聚（ADP - 核糖）聚合酶（PARP）抑制剂，对PARP1、PARP2和PARP3酶具有强效抑制作用。II期和III期试验已证明，鲁卡帕尼对高级别卵巢癌患者具有单药抗肿瘤活性，这些患者既有胚系和体细胞BRCA突变，也有同源重组缺陷（HRD）。鲁卡帕尼作为维持治疗，在对铂类化疗有反应的卵巢癌患者中显示出无进展生存期延长，且安全性可接受。该药物的获批，连同配套诊断FoundationFocus CDxBRCA检测，代表了卵巢癌治疗中一种重要的新治疗选择。本文综述了鲁卡帕尼的作用机制、安全性、药代动力学和药效学、使用指征以及未来试验。
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Eur J Cancer. 2017 Nov;86:5-14. doi: 10.1016/j.ejca.2017.08.029. Epub 2017 Sep 23.
2
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Lancet. 2017 Oct 28;390(10106):1949-1961. doi: 10.1016/S0140-6736(17)32440-6. Epub 2017 Sep 12.
3
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Gynecol Oncol. 2017 Nov;147(2):267-275. doi: 10.1016/j.ygyno.2017.08.022. Epub 2017 Sep 4.
4
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Lancet Oncol. 2017 Sep;18(9):1274-1284. doi: 10.1016/S1470-2045(17)30469-2. Epub 2017 Jul 25.
5
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Crit Rev Oncol Hematol. 2017 Jun;114:153-165. doi: 10.1016/j.critrevonc.2017.04.006. Epub 2017 Apr 20.
6
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Science. 2017 Mar 17;355(6330):1152-1158. doi: 10.1126/science.aam7344. Epub 2017 Mar 16.
7
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