Stephenson Oklahoma Cancer Center at the University of Oklahoma, Oklahoma City, OK, USA.
Department of Oncology, Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark.
Gynecol Oncol. 2018 Apr;149(1):214-220. doi: 10.1016/j.ygyno.2018.01.011. Epub 2018 Feb 4.
Niraparib is an oral poly(ADP ribose) polymerase (PARP) inhibitor that is currently approved by the United States Food and Drug Administration (US FDA) as well as recently approved by the European Medicines Agency (EMA) for the maintenance treatment of women with recurrent ovarian cancer who are in complete or partial response to platinum-based chemotherapy. The mechanisms of action of niraparib include inhibition of PARP enzymatic activity as well as increased formation of PARP-DNA complexes through "trapping" the PARP enzyme on damaged DNA. Phase I and III studies have demonstrated activity and benefit of niraparib in both BRCA mutated (BRCAm) and BRCA wild-type (BRCAwt) cancers. Phase I testing of niraparib established the maximally tolerated dose of 300mg by mouth (PO) daily, and the phase 3 ENGOT-OV16/NOVA study demonstrated the benefit of niraparib maintenance therapy compared to placebo after completion of and response to platinum-based chemotherapy in both BRCAm and BRCAwt ovarian cancer patient populations. Toxicities seen with niraparib include hematologic, gastrointestinal, fatigue, and cardiovascular. Hematologic toxicities include thrombocytopenia, anemia, neutropenia and leukopenia; upfront dose modification to 200mg niraparib for patients with baseline weight of ≤77kg and/or baseline platelets of ≤150,000K/uL should be considered to avoid significant hematologic toxicity, especially thrombocytopenia, based on recent analyses of the ENGOT-OV16/NOVA study. Cardiovascular toxicities include hypertension, tachycardia, as well as palpitations, and patients should be monitored for hypertension. PARP inhibitors have been associated with low risks of acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS), and the overall risk of AML and MDS is 0.9% of all patients treated with niraparib. Niraparib testing is ongoing in newly diagnosed ovarian cancer patients as maintenance therapy following completion of platinum-based chemotherapy, in BRCAwt cancers as treatment, as well as in combinations with other biologic drugs such as immunotherapy and anti-angiogenic agents.
尼拉帕利是一种口服聚（ADP 核糖）聚合酶（PARP）抑制剂，目前已被美国食品和药物管理局（FDA）以及欧洲药品管理局（EMA）批准用于治疗对铂类化疗有完全或部分反应的复发性卵巢癌女性患者的维持治疗。尼拉帕利的作用机制包括抑制 PARP 酶的活性以及通过“捕获”PARP 酶在受损 DNA 上形成更多的 PARP-DNA 复合物。I 期和 III 期研究表明，尼拉帕利在 BRCA 突变（BRCAm）和 BRCA 野生型（BRCAwt）癌症中均具有活性和益处。尼拉帕利的 I 期试验确定了每日 300mg 口服（PO）的最大耐受剂量，III 期 ENGOT-OV16/NOVA 研究表明，在 BRCAm 和 BRCAwt 卵巢癌患者人群中，与安慰剂相比，尼拉帕利维持治疗在完成和对铂类化疗有反应后具有益处。尼拉帕利的毒性包括血液学、胃肠道、疲劳和心血管毒性。血液学毒性包括血小板减少症、贫血、中性粒细胞减少和白细胞减少症；对于基线体重≤77kg 和/或基线血小板≤150,000K/uL 的患者，应考虑将尼拉帕利的起始剂量修改为 200mg，以避免严重的血液学毒性，尤其是血小板减少症，这是基于最近对 ENGOT-OV16/NOVA 研究的分析。心血管毒性包括高血压、心动过速以及心悸，应监测患者的高血压情况。PARP 抑制剂与急性髓系白血病（AML）和骨髓增生异常综合征（MDS）的低风险相关，所有接受尼拉帕利治疗的患者中 AML 和 MDS 的总体风险为 0.9%。尼拉帕利正在接受新诊断的卵巢癌患者作为完成铂类化疗后的维持治疗，在 BRCAwt 癌症中作为治疗方法，以及与其他生物药物如免疫疗法和抗血管生成药物联合使用的临床试验中。
