Marom Inbal, Lavie Ofer, Ostrovsky Ludmila, Kugelman Nir, Schmidt Meirav, Segev Yakir
The Lady Davis Carmel Medical Center, Haifa, Israel, affiliated to the Faculty of Medicine at the Technion, Israeli Institute of Technology, Israel.
Harefuah. 2020 Mar;159(3):175-180.
Treatment for ovarian cancer has been challenging for many years. It is composed of debulking surgery and chemotherapy. During the first line of treatment most patients are sensitive to primary platinum-based chemotherapy, however, unfortunately, most of them will suffer from recurrence in 36 months. About 20-25% of ovarian cancer patients exhibit a germ line mutation in the pathway of double strand DNA repair including BRCA. Poly ADP ribose polymerase inhibitors (PARP Inhibitors) may inhibit enzymes responsible for single strand DNA repair, thus leaving the BRCA mutated cell without a repair mechanism for DNA damage leading to synthetic lethality. Recently, phase 3 studies have shown that ovarian cancer patients with recurrent, platinum sensitive disease who were treated with PARP inhibitors have shown statistically significant improvement in progression free survival. A recent pivotal trial has shown the addition of PARP inhibitor, as a maintenance treatment after first line chemotherapy to ovarian cancer patients with BRCA mutation, had significantly increased the progression-free survival. The side effect profile of PARP inhibitors was tolerable and manageable, although they should be well familiar to care givers. Following these studies, the FDA and the European authorities granted an accelerated approval for the use of PARP inhibitors as maintenance treatment after first line treatment, for BRCA carriers, and at the recurrence for platinum sensitive patients. Subsequently, it was added to the benchmark medications for recurrent platinum sensitive BRCA carriers (germ line or somatic) by the Ministry of Health in Israel. The future seams to provide new combination treatments of PARP inhibitors with immunological agents and vascular endothelial growth factors inhibitors aiming to improve the poor prognosis of ovarian cancer patients.
多年来，卵巢癌的治疗一直具有挑战性。其治疗方法包括减瘤手术和化疗。在一线治疗期间，大多数患者对基于铂的初始化疗敏感，然而，不幸的是，其中大多数患者将在36个月内复发。约20%-25%的卵巢癌患者在包括BRCA在内的双链DNA修复途径中存在种系突变。聚ADP核糖聚合酶抑制剂（PARP抑制剂）可能抑制负责单链DNA修复的酶，从而使BRCA突变细胞缺乏DNA损伤修复机制，导致合成致死。最近，3期研究表明，接受PARP抑制剂治疗的复发、铂敏感型卵巢癌患者的无进展生存期有统计学上的显著改善。一项近期的关键试验表明，对于BRCA突变的卵巢癌患者，在一线化疗后添加PARP抑制剂作为维持治疗，可显著提高无进展生存期。PARP抑制剂的副作用是可耐受和可管理的，尽管护理人员应该对其非常熟悉。基于这些研究，美国食品药品监督管理局（FDA）和欧洲当局批准加速使用PARP抑制剂作为一线治疗后的维持治疗，用于BRCA携带者以及铂敏感患者复发时的治疗。随后，以色列卫生部将其添加到复发性铂敏感BRCA携带者（种系或体细胞）的基准药物中。未来似乎会提供PARP抑制剂与免疫制剂和血管内皮生长因子抑制剂的新联合治疗方法，旨在改善卵巢癌患者的不良预后。
