第三个PARP抑制剂Niraparib（商品名Zejula 中文译名 尼拉帕尼)胶囊被批准用於复发性卵巢、输卵管和原发腹膜癌的维持治疗
2017年3月27日，美国食品和药物管理局FDA批准了Niraparib（商品名Zejula, 美国Tesaro公司生产）用於经铂类化疗後完全或部分缓解的复发性卵巢、输卵管和原发腹膜癌的维持治疗。
美国2017年预计有22000人被诊断卵巢、输卵管和原发腹膜癌，大约14000人因这些肿瘤而去世。Niraparib是一个多聚二磷酸腺苷核糖聚合酶抑制剂，它可阻断这种参与修复受损的脱氧核糖核酸的酶。
这项批准是基於一个临床试验的有效结果。553患有复发性卵巢、输卵管和原发腹膜癌的患者，经过至少两次铂类化疗，且在最後一次化疗後达到完全或部分缓解。患者被随即分配接受Niraparib或安慰剂治疗。结果显示，Niraparib可明显延长无进展生存期。
在有乳腺癌易感基因的患者中，经Niraparib治疗的无进展生存期为21个月，而用安慰剂的无进展生存期仅为5.5个月；在没有乳腺癌易感基因的患者中，经Niraparib治疗的无进展生存期为9.3个月，而用安慰剂的无进展生存期则为3.9个月。
作用机制
Niraparib是聚（ADP-核糖）聚合酶（PARP）酶PARP-1和PARP-2的抑制剂，其在DNA修复中起作用。 体外研究已经表明，尼拉帕列诱导的细胞毒性可能涉及PARP酶活性的抑制和PARP-DNA复合物的形成增加导致DNA损伤，凋亡和细胞死亡。 在具有或不具有BRCA1/2缺陷的肿瘤细胞系中观察到增加的尼拉必利诱导的细胞毒性。Niraparib在具有BRCA1/2缺陷的人类癌细胞系的小鼠异种移植模型中以及具有突变型或野生型BRCA1/2的具有同源重组缺陷的人类患者衍生的异种移植肿瘤模型中降低肿瘤生长。
适应证和用途
ZEJULA是一种聚(ADP-核糖)聚合酶(PARP)抑制剂；适用复发性表皮卵巢，输卵管，或原发性腹膜癌患者对基于铂化疗是一个完全或部分缓解成年患者的维持治疗。
剂量和给药方法
● 推荐剂量为300毫克，口服，每天一次。
剂型和规格
ZEJULA为胶囊有一个白色体部用黑墨水印有“100mg”，和一个紫色帽用白色水印有“Niraparib”。每粒胶囊含100mg的niraparib。
ZEJULA胶囊被包装为90-计数瓶NDC 69656-103-90
贮存在20°至25°C(68°至77°F)；外出允许15°C至30°C间(59°F至86°F)[见USP控制室温]。

若需完整的处方信息，请访问：
https://dailymed.nlm.nih.gov/dailyme (niraparib)d/drugInfo.cfm?setid=0fe9d533-67a9-4981-978a-1e84755ae30b
Zejula Approved for Recurrent Ovarian Cancer, Primary Peritoneal Cancer
The Food and Drug Administration (FDA) has approved Zejula (niraparib capsules; Tesaro) for the maintenance treatment of adults with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. Zejula is the first poly (ADP-ribose) polymerase (PARP) inhibitor to be approved by the FDA that does not require BRCA mutation or other biomarker testing.
“Until recently, there have been few treatment advances for women with recurrent ovarian cancer and even fewer options available for women who do not harbor BRCA mutations," said Dr. Ursula Matulonis, MD, Director, Gynecologic Oncology at Dana-Farber Cancer Institute and Professor of Medicine, Harvard Medical School.
The FDA approval was supported by data from NOVA, a randomized trial (n=533) of patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who received ≥2 prior treatments of platinum-based chemotherapy and were in a complete or partial response to the most recent treatment. Patients were randomized to either niraparib 300mg daily or placebo.
Based on their BRCA analysis CDx, patients with deleterious or suspected deleterious germline BRCA mutations (gBRCAm) were assigned to the germline BRCA-mutated (gBRCAmut) cohort (n=203), and those without germline BRCA mutations were assigned to the non-gBRCAmut cohort (n=350).  
The results showed a statistically significant improvement in progression-free survival (PFS) for niraparib patients vs. placebo in both cohorts. The estimated median PFS for those taking niraparib who had a germline BRCA mutation was 21months vs. 5.5months for those in the gBRCAmut cohort taking placebo (hazard ratio[HR]0.26, 95% CI: 0.17, 0.41; P<0.0001). The estimated median PFS for niraparib patients without a germline BRCA mutation was 9.3months vs. 3.9months for those in the non-gBRCAmut cohort receiving placebo (HR 0.45, 95% CI: 0.34, 0.61, P<0.0001).
The safety analysis (n=367) found the most common adverse reactions to be thrombocytopenia, anemia, neutropenia, leukopenia, palpitations, nausea, constipation, vomiting, abdominal pain/distention, mucositis/stomatitis, diarrhea, and others.
Zejula is an inhibitor of PARP enzymes, PARP-1 and PARP-2, which play a role in DNA repair. Zejula-induced  cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes resulting in DNA damage, apoptosis and cell death.
Zejula will be available as 100mg strength capsules in 90-count bottles.
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208447lbl.pdf