Gonzalez Anna, Kistenfeger Quinn, Cosgrove Casey M
Division of Gynecologic Oncology; The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute, Columbus, OH, USA.
Division of Obstetrics & Gynecology; The Ohio State University, Columbus, OH, USA.
Int J Womens Health. 2024 Dec 20;16:2239-2246. doi: 10.2147/IJWH.S466250. eCollection 2024.
The advent of poly(ADP-ribose) polymerase (PARP) inhibitors has resulted in a significant paradigm shift in ovarian cancer treatment. Niraparib, a potent PARP inhibitor, has demonstrated substantial efficacy in both first-line and recurrent disease settings. By targeting homologous recombination DNA repair, a pathway frequently disrupted in ovarian cancer, particularly in the context of BRCA mutations, niraparib induces synthetic lethality. Pivotal clinical trials, including PRIMA, ENGOT-OV16/NOVA, and QUADRA, have solidified niraparib's role in the treatment paradigm. While sharing a common mechanism of action with other PARP inhibitors, niraparib exhibits a distinct toxicity profile. Notably, hematologic toxicities, particularly thrombocytopenia, and hypertension have been observed at Grade 3-4 levels. A comprehensive understanding of niraparib's efficacy and safety is essential for optimal patient selection and management.
聚(ADP - 核糖)聚合酶(PARP)抑制剂的出现使卵巢癌治疗发生了重大的模式转变。尼拉帕利是一种强效PARP抑制剂,在一线和复发性疾病治疗中均显示出显著疗效。通过靶向同源重组DNA修复(这是一种在卵巢癌中经常被破坏的途径,特别是在BRCA突变的情况下),尼拉帕利诱导合成致死。包括PRIMA、ENGOT - OV16/NOVA和QUADRA在内的关键临床试验巩固了尼拉帕利在治疗模式中的作用。虽然与其他PARP抑制剂具有共同的作用机制,但尼拉帕利表现出独特的毒性特征。值得注意的是,已观察到3 - 4级的血液学毒性,尤其是血小板减少症和高血压。全面了解尼拉帕利的疗效和安全性对于优化患者选择和管理至关重要。