Steffensen Karina Dahl, Adimi Parvin, Jakobsen Anders
*Department of Oncology, Vejle Hospital, Vejle; †Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark.
Int J Gynecol Cancer. 2017 Nov;27(9):1842-1849. doi: 10.1097/IGC.0000000000001089.
A new treatment principle, which seems to radically change the treatment approach in ovarian cancer (OC), has developed over the past few years. Poly(ADP-ribose) polymerase inhibitors work by interfering with mechanisms important to DNA damage repair. Cancer cells that already have defects in the BRCA genes are particularly sensitive to treatment with poly(ADP-ribose) polymerase inhibitors. The main purpose of this study was to investigate the effect of veliparib in patients with known BRCA1/2 mutations and with a platinum-resistant or intermediate sensitive relapse of OC.
Major eligibility criteria were primary epithelial ovarian/fallopian/peritoneal cancer patients with a platinum-resistant or intermediate sensitive relapse of OC and with evaluable disease by either Response Evaluation Criteria In Solid Tumors or Gynecological Cancer Intergroup CA-125 criteria. Patients were treated with oral veliparib twice daily on days 1 to 28.
Sixteen patients were enrolled in the phase I part, and a maximum tolerable dose of 300 mg twice daily was established. The phase II part enrolled 32 patients with a median of 4 previous treatment regimens. The overall response rate combining Response Evaluation Criteria In Solid Tumors and CA-125 response was 65% (6% complete response and 59% partial response). Progression-free and overall survival rates of the intention-to-treat population were 5.6 months (95% confidence interval, 5.2-7.3 months) and 13.7 months (95% confidence interval, 10.2-17.3 months), respectively. The most common phase II treatment-related grade 2 toxicities included fatigue (22%), nausea (22%), and vomiting (9%).
Treatment with veliparib in heavily pretreated patients with relapse of OC demonstrates a considerable efficacy with an acceptable toxicity profile.
在过去几年中，一种似乎能从根本上改变卵巢癌（OC）治疗方法的新治疗原则已经形成。聚（ADP - 核糖）聚合酶抑制剂通过干扰对DNA损伤修复至关重要的机制发挥作用。已经存在BRCA基因缺陷的癌细胞对聚（ADP - 核糖）聚合酶抑制剂治疗特别敏感。本研究的主要目的是调查维利帕尼对已知有BRCA1/2突变且铂耐药或铂中度敏感复发的OC患者的疗效。
主要入选标准为原发性上皮性卵巢/输卵管/腹膜癌患者，有铂耐药或铂中度敏感复发的OC，且根据实体瘤疗效评价标准或妇科肿瘤协作组CA - 125标准疾病可评估。患者在第1至28天每天口服维利帕尼两次。
16名患者入组I期研究部分，确定最大耐受剂量为每日两次300毫克。II期研究部分入组32名患者，这些患者既往治疗方案中位数为4种。综合实体瘤疗效评价标准和CA - 125反应的总缓解率为65%（完全缓解率6%，部分缓解率59%）。意向性治疗人群的无进展生存率和总生存率分别为5.6个月（95%置信区间，5.2 - 7.3个月）和13.7个月（95%置信区间，10.2 - 17.3个月）。II期最常见的与治疗相关的2级毒性包括疲劳（22%）、恶心（22%）和呕吐（9%）。
在接受过大量治疗的OC复发患者中使用维利帕尼治疗显示出相当大的疗效，且毒性可接受。
