Phase II trial of thalidomide for therapy of radioiodine-unresponsive and rapidly progressive thyroid carcinomas
Phase II trial of thalidomide for therapy of radioiodine-unresponsive and rapidly progressive thyroid carcinomas
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DOI：
10.1089/thy.2006.0289
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发表时间：
2007-08-01
期刊：
影响因子：
6.6
通讯作者：
Williams, Kevin D.
中科院分区：
文献类型：
--
作者：
Ain, Kenneth B.;Lee, Charles;Williams, Kevin D.
背景：对于对放射性碘无反应的远处转移、快速进展的甲状腺癌，尚无已知的有效治疗方法。目的：由于甲状腺癌血管丰富，而沙利度胺具有抗血管生成作用，我们在一项II期试验中评估了沙利度胺的抗肿瘤作用和毒性。设计：在2001年7月至2002年12月期间，收治36例甲状腺滤泡癌、乳头状癌、岛状癌或髓样癌以及远处放射性碘反应不敏感的转移瘤(入组前体积每年增加30%)。每日沙利度胺从200毫克开始，在6周内增加到800毫克或最大耐受量。通过肿瘤体积评估，每隔8周评估一次毒性和反应。主要结果：36例患者中28例可评价，5例部分缓解(PR：18%；95%可信区间[95%CI]：6-37%)，9例病情稳定(SD：32%；95%CI：12-42%)，总有效率为50%(95%CI：31-69%)。中位PR期4个月(2~6个月)，SD期6个月(2~14个月)。有反应者(PR+SD)的中位生存期为23.5个月，无反应者为11个月。最常见的毒性是疲劳(1-2级占69%，3-4级占8%)。4例患者有3-4级感染(无中性粒细胞减少)，1例有心包积液，1例有肺血栓。结论：沙利度胺对有快速进展和远处转移疾病的甲状腺癌患者亚群具有治疗益处。
Background: There are no known effective therapies for distantly metastatic, rapidly progressive thyroid carcinomas unresponsive to radioiodine. Objective: Since thyroid carcinomas are hypervascular and thalidomide is anti-angiogenic, we assessed thalidomide's tumoristatic effects and toxicity in a phase II trial. Design: Thirty-six patients with follicular, papillary, insular, or medullary thyroid carcinomas and distant, radioiodine-unresponsive metastases (volumes increasing >= 30% per year before entry) were accrued between July 2001 and December 2002. Daily thalidomide started at 200 mg, increasing over 6 weeks to 800 mg or maximum tolerated dose. Toxicities and responses were assessed at 8-week intervals with tumor volume assessments. Main outcomes: Twenty-eight of 36 patients were evaluable, 5 with partial responses (PR: 18%; 95% confidence interval [95% CI]: 6-37%) and 9 patients with stable disease (SD: 32%; 95% CI: 12-42%) for overall 50% response (95% CI: 31-69%). Median PR duration was 4 months (range: 2-6 months), and SD duration was 6 months (range: 2-14 months). Median survival was 23.5 months for responders (PR + SD) and 11 months for nonresponders. Most frequent toxicity was fatigue (69% grade 1-2, 8% grade 3-4). Four patients had grade 3-4 infections (without neutropenia), one had pericardial effusion, and one had pulmonary embolus. Conclusions: Thalidomide confers therapeutic benefit in subsets of thyroid cancer patients with rapidly progressive, distantly metastatic disease.