Head and Neck Unit, The Royal Marsden NHS Foundation Trust, Fulham Road, London SW3 6JJ, UK.
Eur J Endocrinol. 2011 Aug;165(2):315-22. doi: 10.1530/EJE-11-0129. Epub 2011 May 12.
To evaluate the tolerability and efficacy of sorafenib in patients with thyroid carcinoma.
Patients with progressive locally advanced/metastatic medullary thyroid carcinoma (MTC), or differentiated thyroid carcinoma (DTC) with non-radioiodine-avid disease, were treated with sorafenib 400 mg twice daily until disease progression. The primary endpoint was the radiological response rate (RR) at 6 months. Secondary endpoints were RR at 3, 9 and 12 months, biochemical responses, toxicity, biomarker analyses and progression free and overall survival (OS).
A total of 34 patients were recruited to the study (15 medullary and 19 differentiated). After 6 months, the RR rate was 15% and a further 74% of patients achieved stable disease in the first 6 months. After 12 months of treatment, the RR was 21%. In the MTC patients, the RR at 12 months was 25% and OS was 100%. In DTC patients corresponding rates were 18 and 79% respectively. Median overall and progression-free survival points were not reached at 19 months. Commonest adverse events included hand-foot syndrome, other skin toxicities, diarrhoea and alopecia. Dose reduction was required in 79% patients. Median time on treatment was 16.5 months.
This study demonstrates that sorafenib is tolerable at reduced doses over prolonged periods of time in patients with thyroid cancer. Sorafenib leads to radiological and biochemical stabilisation of disease in the majority of these patients despite dose reductions.
评估索拉非尼治疗甲状腺癌患者的耐受性和疗效。
进展期局部晚期/转移性甲状腺髓样癌（MTC）或非放射性碘难治性分化型甲状腺癌（DTC）患者接受索拉非尼 400mg，每日两次治疗，直至疾病进展。主要终点为 6 个月时的影像学缓解率（RR）。次要终点为 3、9 和 12 个月时的 RR、生化缓解、毒性、生物标志物分析以及无进展生存期（PFS）和总生存期（OS）。
共有 34 例患者入组研究（15 例 MTC，19 例 DTC）。6 个月时，RR 率为 15%，另有 74%的患者在最初 6 个月内达到疾病稳定。治疗 12 个月后，RR 为 21%。在 MTC 患者中，12 个月时的 RR 为 25%，OS 为 100%。在 DTC 患者中，相应的 RR 和 OS 分别为 18%和 79%。中位总生存期和无进展生存期未达到 19 个月。最常见的不良反应包括手足综合征、其他皮肤毒性、腹泻和脱发。79%的患者需要减少剂量。中位治疗时间为 16.5 个月。
本研究表明，索拉非尼在甲状腺癌患者中可耐受长时间、低剂量治疗。尽管剂量减少，索拉非尼仍能使大多数患者的疾病在影像学和生化上得到稳定。
