Program in Women's Oncology, Women & Infants Hospital/Alpert Medical School of Brown University, Providence, RI, United States.
Gynecol Oncol. 2012 May;125(2):367-71. doi: 10.1016/j.ygyno.2012.02.019. Epub 2012 Feb 21.
Patients with recurrent ovarian cancer have limited options, especially in the context of relapse less than six months from primary platinum-based therapy. This Gynecologic Oncology Group (GOG) study was conducted to evaluate the impact of the histone deacetylase inhibitor, belinostat, in combination with carboplatin in women with platinum-resistant ovarian cancer.
Eligible patients had measurable, recurrent disease within six months of their last dose of a platinum-based combination. Belinostat was dosed at 1000 mg/m(2) daily for five days with carboplatin AUC 5 on day three of 21-day cycles. The primary endpoint was overall response rate (ORR), using a two-stage design.
Twenty-nine women enrolled on study and 27 were evaluable. The median number of cycles given was two (range 1-10). One patient had a complete response and one had a partial response, for an ORR of 7.4% (95% CI, .9%-24.3%). Twelve patients had stable disease while eight had increasing disease. Response could not be assessed in five (18.5%). Grade 3 and 4 events occurring in more than 10% of treated patients were uncommon and limited to neutropenia (22.2%), thrombocytopenia (14.8%), and vomiting (11.1%). The median progression-free survival (PFS) was 3.3 months and overall survival was 13.7 months. PFS of at least six months was noted in 29.6% of patients. Due to the lack of drug activity, the study was closed after the first-stage.
The addition of belinostat to carboplatin had little activity in a population with platinum-resistant ovarian cancer.
复发性卵巢癌患者的选择有限，尤其是在铂类药物治疗后不到 6 个月复发的情况下。这项妇科肿瘤学组（GOG）研究旨在评估组蛋白去乙酰化酶抑制剂贝林司他联合卡铂在铂类耐药卵巢癌患者中的作用。
符合条件的患者在末次铂类联合治疗后 6 个月内有可测量的复发性疾病。贝林司他的剂量为 1000mg/m2，每日一次，连用 5 天，卡铂 AUC 为 5，每 21 天周期的第 3 天使用。主要终点是总缓解率（ORR），采用两阶段设计。
29 名女性入组，27 名可评估。中位周期数为 2 个（范围 1-10）。1 例患者完全缓解，1 例部分缓解，ORR 为 7.4%（95%CI，0.9%-24.3%）。12 例患者病情稳定，8 例病情进展。5 例（18.5%）无法评估反应。发生率超过 10%的 3 级和 4 级事件罕见，限于中性粒细胞减少症（22.2%）、血小板减少症（14.8%）和呕吐（11.1%）。中位无进展生存期（PFS）为 3.3 个月，总生存期为 13.7 个月。至少 6 个月 PFS的患者占 29.6%。由于药物无活性，该研究在第一阶段后关闭。
在铂类耐药卵巢癌患者中，贝林司他联合卡铂的活性较低。
