A phase II evaluation of cediranib in the treatment of recurrent or persistent endometrial cancer: An NRG Oncology/Gynecologic Oncology Group study.
A phase II evaluation of cediranib in the treatment of recurrent or persistent endometrial cancer: An NRG Oncology/Gynecologic Oncology Group study.
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DOI：
10.1016/j.ygyno.2015.07.018
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发表时间：
2015-09
影响因子：
4.7
通讯作者：
Leslie KK
中科院分区：
文献类型：
--
作者：
Bender D;Sill MW;Lankes HA;Reyes HD;Darus CJ;Delmore JE;Rotmensch J;Gray HJ;Mannel RS;Schilder JM;Hunter MI;McCourt CK;Samuelson MI;Leslie KK
Cediranib是一种多酪氨酸激酶抑制剂，靶向血管内皮生长因子（VEGF）、血小板衍生生长因子（PDGF）和成纤维细胞生长因子（FGF）受体。这项II期研究旨在评估西地尼布单药治疗复发性/持续性子宫内膜癌的活性和耐受性。合格患者在接受一种或两种既往细胞毒性方案治疗后患有复发性或持续性子宫内膜癌，疾病可测量，妇科肿瘤组（GOG）体能状态≤2（如果接受了两种既往细胞毒性方案治疗，则≤1）。每天口服西地尼布30 mg，持续28天周期，直至疾病进展或出现抑制性毒性。在子宫切除术标本中测量肿瘤组织中的微血管密度（MVD），并与临床结果相关。主要终点是肿瘤缓解和无进展生存6个月，无需后续治疗（6个月无事件生存期[EFS]）。在入组的53例患者中，48例可评价西地尼布的疗效和毒性。中位年龄为65.5岁，52%的患者既往接受过放疗，73%的患者既往仅接受过一种化疗方案。在12.5%的患者中观察到部分缓解。14例患者（29%）有6个月EFS。中位无进展生存期（PFS）为3.65个月，中位总生存期（OS）为12.5个月。未观察到4级或5级毒性。在肿瘤表达高MVD的患者中发现PFS改善的趋势。Cediranib作为复发性或持续性子宫内膜癌的单药治疗耐受性良好，并且达到了方案设定的目标，即有足够的活性来保证进一步的研究。MVD可能是一个有用的生物标志物的活动。
Cediranib is a multi-tyrosine kinase inhibitor targeting vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF) receptors. This phase II study was conducted to assess activity and tolerability of single-agent cediranib in recurrent/persistent endometrial cancer. Eligible patients had recurrent or persistent endometrial cancer after receiving one or two prior cytotoxic regimens, measurable disease, and Gynecologic Oncology Group (GOG) performance status of ≤2 (≤1 if two prior cytotoxic regimens given). Cediranib 30 mg orally daily for a 28 day cycle was administered until disease progression or prohibitive toxicity. Microvessel density (MVD) was measured in tumor tissue from initial hysterectomy specimens and correlated with clinical outcome. Primary endpoints were tumor response and surviving progression-free for six months without subsequent therapy (6-month event-free survival [EFS]). Of 53 patients enrolled, 48 were evaluable for cediranib efficacy and toxicity. Median age was 65.5 years, 52% of patients had received prior radiation, and 73% of patients received only one prior chemotherapy regimen. A partial response was observed in 12.5%. Fourteen patients (29%) had six-month EFS. Median progression-free survival (PFS) was 3.65 months and median overall survival (OS) 12.5 months. No grade 4 or 5 toxicities were observed. A trend towards improved PFS was found in patients whose tumors expressed high MVD. Cediranib as a monotherapy treatment for recurrent or persistent endometrial cancer is well tolerated and met protocol set objectives for sufficient activity to warrant further investigation. MVD may be a useful biomarker for activity.