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The Lancet:索拉非尼对分化型甲状腺癌患者有效

来源:生物谷 2014-04-28 18:26

2014年4月26日讯 /生物谷BIOON/--根据宾夕法尼亚大学Abramson癌症中心一项新的研究证实,与安慰剂组相比,肾癌和肝癌治疗药物索拉非尼能延长转移性甲状腺癌患者生存期。相关研究论文发表在柳叶刀上。

这个随机III期临床试验的初步结果公布在2013年临床肿瘤年会上。索拉非尼于2013年11月被FDA批准用于局部复发型或转移型,进展型,分化型、放射性碘难治性甲状腺癌的治疗。这些患者此前只有有限的治疗选择。

通过手术和放射性碘治疗,甲状腺癌是高度可医治,但每年被诊断出患有这种疾病的60,000名患者中,大约10%的患者对标准治疗没有反应,肿瘤最终会出现在肺,淋巴结,骨骼和其他组织。唯一治疗晚期甲状腺癌的药物是阿霉素,于1974年批准,但因为它是剧毒已经不被使用。

直到开始使用索拉非尼,Marcia S. Brose博士表示:现在,我们可以给患者希望,表明一个突破性药物可以阻止疾病的进展,这项试验是一系列临床试验的第一步,以确定晚期分化型甲状腺癌的新药。

在这项多中心,国际临床研究中,涉及到417例转移性甲状腺癌患者,207名随机给予索拉非尼,以及210名给予安慰剂。该研究达到了主要终点,服用索拉非尼的患者,中位无进展生存期为10.8个月,其中安慰剂组为5.8个月。

索拉非尼组患者肿瘤缩小12%,服用安慰剂的患者为0.5%。服用索拉非尼的患者中观察到的最常见不良反应包括手足皮肤反应,腹泻,脱发,皮疹,乏力,消瘦,高血压,所有这些都是可控的。

该研究还表明,索拉非尼提高了所有亚组和BRAF或RAS基因突变患者无进展生存期,BRAF或RAS基因突变在放射性碘难治性分化型甲状腺癌中是常见的。因此,这些突变不是能预测索拉非尼治疗癌症的生物标志物。

索拉非尼将是第一个有效且耐受性良好的药物,以改善放射性碘难治性和恶性分化型甲状腺癌病人的结果。(生物谷Bioon.com)

Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial

Dr Marcia S Brose,et al.

Background
Patients with radioactive iodine (131I)-refractory locally advanced or metastatic differentiated thyroid cancer have a poor prognosis because of the absence of effective treatment options. In this study, we assessed the efficacy and safety of orally administered sorafenib in the treatment of patients with this type of cancer.
Methods
In this multicentre, randomised, double-blind, placebo-controlled, phase 3 trial (DECISION), we investigated sorafenib (400 mg orally twice daily) in patients with radioactive iodine-refractory locally advanced or metastatic differentiated thyroid cancer that had progressed within the past 14 months. Adult patients (≥18 years of age) with this type of cancer were enrolled from 77 centres in 18 countries. To be eligible for inclusion, participants had to have at least one measurable lesion by CT or MRI according to Response Evaluation Criteria In Solid Tumors (RECIST); Eastern Cooperative Oncology Group performance status 0—2; adequate bone marrow, liver, and renal function; and serum thyroid-stimulating hormone concentration lower than 0·5 mIU/L. An interactive voice response system was used to randomly allocate participants in a 1:1 ratio to either sorafenib or matching placebo. Patients, investigators, and the study sponsor were masked to treatment assignment. The primary endpoint was progression-free survival, assessed every 8 weeks by central independent review. Analysis was by intention to treat. Patients in the placebo group could cross over to open-label sorafenib upon disease progression. Archival tumour tissue was examined for BRAF and RAS mutations, and serum thyroglobulin was measured at baseline and at each visit. This study is registered with ClinicalTrials.gov, number NCT00984282, and with the EU Clinical Trials Register, number EudraCT 2009—012007—25.
Findings
Patients were randomly allocated on a 1:1 basis to sorafenib or placebo. The intention-to-treat population comprised 417 patients (207 in the sorafenib group and 210 in the placebo group) and the safety population was 416 patients (207 in the sorafenib group and 209 in the placebo group). Median progression-free survival was significantly longer in the sorafenib group (10·8 months) than in the placebo group (5·8 months; hazard ratio [HR] 0·59, 95% CI 0·45—0·76; p<0·0001). Progression-free survival improved in all prespecified clinical and genetic biomarker subgroups, irrespective of mutation status. Adverse events occurred in 204 of 207 (98·6%) patients receiving sorafenib during the double-blind period and in 183 of 209 (87·6%) patients receiving placebo. Most adverse events were grade 1 or 2. The most frequent treatment-emergent adverse events in the sorafenib group were hand—foot skin reaction (76·3%), diarrhoea (68·6%), alopecia (67·1%), and rash or desquamation (50·2%).
Interpretation
Sorafenib significantly improved progression-free survival compared with placebo in patients with progressive radioactive iodine-refractory differentiated thyroid cancer. Adverse events were consistent with the known safety profile of sorafenib. These results suggest that sorafenib is a new treatment option for patients with progressive radioactive iodine-refractory differentiated thyroid cancer.

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