随机 III 期试验：在一线含铂/紫杉化疗完全缓解后，仅发生生化复发的上皮性卵巢癌、输卵管癌或原发性腹膜癌患者中，比较他莫昔芬与沙利度胺的疗效，评估血清血管内皮生长因子（VEGF）：一项妇科肿瘤学组研究。
Randomized phase III trial of tamoxifen versus thalidomide in women with biochemical-recurrent-only epithelial ovarian, fallopian tube or primary peritoneal carcinoma after a complete response to first-line platinum/taxane chemotherapy with an evaluation of serum vascular endothelial growth factor (VEGF): A Gynecologic Oncology Group Study.
机构信息
NorthShore University Health System Division of GYN Oncology, Department of Obstetrics and Gynecology, University of Chicago Pritzker School of Medicine, Evanston Hospital, Evanston, IL 60201, USA.
出版信息
Gynecol Oncol. 2010 Dec;119(3):444-50. doi: 10.1016/j.ygyno.2010.08.002. Epub 2010 Sep 17.
PURPOSE
To compare progression-free survival (PFS), overall survival (OS) and toxicities of thalidomide versus tamoxifen and to evaluate serum vascular endothelial growth factor (VEGF) in biochemical-recurrent epithelial ovarian cancer, primary peritoneal cancer or fallopian tube carcinoma (EOC/PPC/FTC).
METHODS
Biochemical recurrence was defined as a rising CA-125 exceeding twice the upper limit of normal without evidence of disease as defined by RECIST 1.0 criteria. Women with FIGO stages III and IV, histologically confirmed EOC/PPC/FTC who were free of disease following first-line chemotherapy were randomized to oral thalidomide 200mg daily with escalation to a maximum of 400 mg or tamoxifen 20mg orally twice daily for up to 1 year, progression or adverse effect prohibited further treatment. VEGF was quantified by ELISA in pre and post-treatment serum.
RESULTS
Of the 139 women randomized, 138 were eligible. Interim analysis showed that thalidomide did not reduce the recurrence rate relative to tamoxifen, and the trial was closed. Thalidomide versus tamoxifen was associated with a similar risk of progression (HR = 1.31, 95% confidence interval [CI] = 0.93-1.85), an increased risk of death (HR = 1.76, 95% CI = 1.16-2.68) and more grades 3 and 4 toxicities (55% versus 3%). The most common grades 3 and 4 toxicities were constitutional (12%), somnolence (12%), pulmonary (9%), venous thromboembolism (VTE) (6%) and peripheral neurologic (6%) for thalidomide, with VTE (1.4%) and gastrointestinal (1.4%) for tamoxifen. Serum VEGF was not associated with clinical characteristics, treatment, PFS or OS.
CONCLUSION
Thalidomide was not more effective than tamoxifen in delaying recurrence or death but was more toxic. VEGF was not prognostic in this cohort.
目的
比较沙利度胺与他莫昔芬在无进展生存期（PFS）、总生存期（OS）和毒性方面的差异，并评估血管内皮生长因子（VEGF）在生化复发性上皮性卵巢癌、原发性腹膜癌或输卵管癌（EOC/PPC/FTC）中的作用。
方法
生化复发定义为 CA-125 升高超过正常上限的两倍，且无 RECIST 1.0 标准定义的疾病证据。FIGO 分期为 III 期和 IV 期、组织学证实的 EOC/PPC/FTC 患者，在一线化疗后无疾病者随机分为口服沙利度胺 200mg/d，可逐步增至最大剂量 400mg/d，或他莫昔芬 20mg 口服，每日 2 次，最长 1 年，出现进展或不良反应时禁止进一步治疗。采用 ELISA 法检测治疗前后血清 VEGF 水平。
结果
在 139 例随机患者中，138 例符合条件。中期分析显示，与他莫昔芬相比，沙利度胺并未降低复发率，因此试验提前关闭。与他莫昔芬相比，沙利度胺的进展风险相似（HR=1.31，95%置信区间[CI]：0.93-1.85），死亡风险增加（HR=1.76，95%CI：1.16-2.68），3 级和 4 级毒性更多（55%比 3%）。最常见的 3 级和 4 级毒性为全身性（12%）、嗜睡（12%）、肺部（9%）、静脉血栓栓塞（VTE）（6%）和周围神经病变（6%），他莫昔芬组为 VTE（1.4%）和胃肠道（1.4%）。血清 VEGF 与临床特征、治疗、PFS 或 OS 均无关。
结论
与他莫昔芬相比，沙利度胺在延迟复发或死亡方面并无优势，且毒性更大。在本队列中，VEGF 无预后价值。
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