Department of Obstetrics and Gynecology, Gynecologic Oncology Section, University of Oklahoma, Oklahoma City, OK 73104, USA.
Gynecol Oncol. 2012 Nov;127(2):356-61. doi: 10.1016/j.ygyno.2012.07.095. Epub 2012 Jul 14.
To evaluate the efficacy and adverse events of thalidomide in previously-treated, measurable, persistent or recurrent carcinosarcoma of the uterus, and to explore associations between angiogenic markers with patient demographics and clinical outcome.
Eligible, consenting patients were treated until disease progression or toxicity intervened with daily starting dose of 200 mg thalidomide/day that was increased by 200 mg every 2 weeks to a target dose of 1000 mg/day. Endpoints included progression-free survival (PFS)≥6 months (primary), toxicity, response, overall PFS and survival. Pre- and post-treatment plasma were evaluated for a panel of angiogenic biomarkers and assessed against clinical outcomes.
Of 55 enrolled patients, 45 were evaluable for toxicity and survival. Two patients (4%; 90% CI 1-13%) experienced a partial response, and 8 (18%; 90% CI 9-30%) had PFS≥6 months. Median PFS was 1.9 months and median survival was 5.9 months. Grade 2-3 sensory neuropathy was noted in 6 patients, and 4, 3, and 3 patients experienced grade 3 sedation, fatigue, and constipation, respectively. Three patients had grade 4 adverse events (2 thromboembolic, 1 anemia). High pre-treatment VEGFA levels were associated with poorer PFS and survival.
Treatment with thalidomide met the protocol specified goal of prolonging PFS at 6 months. However, based on results with newer agents, the activity was insufficient to support further investigation. Association between pre-treatment VEGFA and prognosis in this population supports further evaluation of anti-angiogenic therapies in uterine carcinosarcoma.
评估沙利度胺治疗既往治疗、可测量、持续性或复发性子宫癌肉瘤的疗效和不良事件，并探讨血管生成标志物与患者人口统计学特征和临床结局之间的关系。
符合条件并同意的患者接受治疗，直至疾病进展或毒性介入，每天起始剂量为 200mg 沙利度胺，每 2 周增加 200mg，目标剂量为 1000mg/天。终点包括无进展生存期（PFS）≥6 个月（主要终点）、毒性、反应、总 PFS 和生存。评估治疗前后的血浆样本，检测一组血管生成生物标志物，并将其与临床结果进行比较。
在 55 名入组患者中，45 名患者可评估毒性和生存情况。2 名患者（4%；90%CI 1-13%）出现部分缓解，8 名患者（18%；90%CI 9-30%）的 PFS≥6 个月。中位 PFS 为 1.9 个月，中位总生存期为 5.9 个月。6 名患者出现 2-3 级感觉神经病变，3 名、3 名和 3 名患者分别出现 3 级镇静、疲劳和便秘。3 名患者出现 4 级不良事件（2 例血栓栓塞，1 例贫血）。高基线 VEGFA 水平与较差的 PFS 和生存相关。
沙利度胺治疗达到了延长 6 个月 PFS 的方案目标。然而，基于新型药物的结果，其活性不足以支持进一步研究。该人群中 VEGFA 与预后的相关性支持进一步评估抗血管生成治疗在子宫癌肉瘤中的应用。
