索拉非尼(sorafenib)医治转移扩散性甲状腺癌的Ⅱ期临床实验

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所属分类:疗效
摘要

目的:基于Ras-Raf-MAP-ERK讯号和血管内皮生长因子(VEGF)在乳头状甲状腺癌(PTC)中的重要作用,研究人员通过索拉非尼(sorafenib)II期临床实验来考察其对P

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目的:基于Ras-Raf-MAP-ERK信号和血管内皮生长因子(VEGF)在 状甲状腺癌(PTC)中的重要作用,研究人员通过索拉非尼(sorafenib)II期临床试验来考察其对PTC患者RAF和VEGF受体激酶的作用。

索拉非尼(sorafenib)医治转移扩散性甲状腺癌的Ⅱ期临床实验
试验对象与方法:研究的主要评判指标为客观缓解率,其次包括血清甲状腺球蛋白(Tg)情况、功能状况、肿瘤基因型及肿瘤切片检查中的信号抑制情况。采用Simon最大最小双平台设计,A组纳入16或25名未接受过化疗的转移扩散扩散性PTC患者(接受肿瘤切片检查);B组纳入其他亚型甲状腺癌患者或之前接受过化疗的患者,不需进行肿瘤切片。患者口服索拉非尼(sorafenib)治疗,一日两次,共400mg。每两个月通过RECIST(实体瘤医治效果评判标准)评判医治效果。浙江省肿瘤医院(中国科学院大学附属肿瘤医院)核医学科叶雪梅

索拉非尼(sorafenib)医治转移扩散性甲状腺癌的Ⅱ期临床实验
结果:结果发现,41名PTC患者中,其中6名部分缓解(PR; 15%; 95% 可信区间, 6-29),23名患者(56%; 95% 可信区间, 40-72)的肿瘤稳定期超过6个月。PR中位持续期为7.5个月(范围:6-14)。中位无进展存活期为15个月(95% 可信区间, 10 -27.5)。18名可检测到Tg的PTC患者中有14名(78%)Tg下降超过25%。常见的3级不良反应包括手脚皮肤反应、肌肉骨骼疼痛及疲劳。22名接受检测的PTC患者中有17位(77%)存在BRAF基因变异。从PTC患者获得的10对肿瘤切片其中4对显示血管内皮生长因子受体磷酸化水平、ERK磷酸化水平及索拉非尼(sorafenib)治疗期间的VEGF表达均下降。而非PTC患者未见症状缓解。
结论:因此研究人员得出结论,索拉非尼(sorafenib)对转移扩散扩散性PTC有临床及生物学抗癌活性,且耐受良好。

PURPOSE: Based on the pivotal role of Ras-Raf-MAP-ERK signaling and vascular endothelial growth factor (VEGF) in papillary thyroid cancer (PTC), we conducted a phase II clinical trial of sorafenib targeting RAF and VEGF receptor kinases in PTC. PATIENTS AND METHODS: The pri ry end point was the objective response rate. Secondary end points included response correlation with serum thyroglobulin (Tg); functional i ging; tumor genotype; and signaling inhibition in tumor biopsies. Using a Simon mini x two-stage design, 16 or 25 chemotherapy- metastatic PTC patients were to be enrolled in arm A (accessible tumor for biopsy). Arm B patients had other subtypes of thyroid carcino or prior chemotherapy, and did not require tumor biopsies. Patients received 400 mg orally twice per day of sorafenib. Response was assessed every 2 months using RECIST (Response Evaluation Criteria in Solid Tumors). RESULTS: Of 41 PTC patients, six patients had a partial response (PR; 15%; 95% CI, 6 to 29) and 23 patients (56%; 95% CI, 40 to 72) had stable disease longer than 6 months. Median duration of PR was 7.5 months (range, 6 to 14). Median progression-free survival was 15 months (95% CI, 10 to 27.5). In 14 (78%) of 18 Tg-assessable PTC patients, Tg declined more than 25%. Common grade 3 adverse events included hand-foot skin reaction, musculoskeletal pain, and fatigue. BRAF mutation was detected in 17 (77%) of 22 PTCs yzed. Four of 10 paired tumor biopsies from PTC patients showed a reduction in levels of vascular endothelial growth factor receptor phosphorylation, ERK phosphorylation, and in VEGF expression during sorafenib therapy. No PRs were noted among non-PTC patients. CONCLUSION: Sorafenib is reasonably well-tolerated therapy with clinical and biologic antitumor activity in metastatic PTC.

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