1 Endocrinology Department; Instituto do Câncer do Estado de São Paulo , Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil .
2 Medical Oncology Department; Instituto do Câncer do Estado de São Paulo , Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil .
Thyroid. 2016 Mar;26(3):414-9. doi: 10.1089/thy.2015.0334. Epub 2016 Feb 9.
Treatment of advanced medullary thyroid carcinoma (MTC) was recently improved with the approval of vandetanib and cabozantinib. However, there is still a need to explore sequential therapy with more than one tyrosine kinase inhibitor (TKI) and to explore alternative therapies when vandetanib and cabozantinib are not available. This study reports the authors' experience with sorafenib as a treatment for advanced MTC.
This is a retrospective longitudinal study of 13 patients with progressive metastatic MTC treated with sorafenib 400 mg twice daily between December 2011 and January 2015. The primary endpoints were to evaluate response and progression-free survival (PFS) in patients treated with sorafenib outside a clinical trial. The secondary endpoint was an assessment of the toxicity profile. One patient was excluded because of a serious allergic skin rash one week after starting sorafenib.
The analysis included 12 patients with metastatic MTC (median age 48 years), 10 with sporadic and 2 with hereditary disease. The median duration of treatment was 11 months, and the median follow-up was 15.5 months. At data cutoff, 2/12 (16%) patients were still on treatment for 16 and 34 months. According to Response Evaluation Criteria in Solid Tumors analysis, 10 (83.3%) patients showed stable disease, and two (16.6%) had progression of disease; no partial response was observed. The median PFS was nine months. However, three patients with extensive and rapidly progressive disease died within three months of sorafenib treatment. The median PFS excluding these three patients was 12 months. Adverse events (AE) occurred in nine (75%) patients. The main AEs were skin toxicity, weight loss, and fatigue. Five (41.6%) patients needed dose reduction, and one patient discontinued treatment because of toxicity.
Treatment with sorafenib in progressive metastatic MTC is well tolerated and resulted in disease control and durable clinical benefit in 75% of patients. Sorafenib treatment could be considered when vandetanib and cabozantinib are not available or after failing these drugs.
随着凡德他尼和卡博替尼的批准，晚期甲状腺髓样癌（MTC）的治疗最近得到了改善。然而，仍然需要探索一种以上的酪氨酸激酶抑制剂（TKI）的序贯治疗方法，并在凡德他尼和卡博替尼不可用时探索替代疗法。本研究报告了作者使用索拉非尼治疗晚期 MTC 的经验。
这是一项回顾性纵向研究，纳入了 13 名在 2011 年 12 月至 2015 年 1 月期间接受索拉非尼 400mg 每日两次治疗的进展性转移性 MTC 患者。主要终点是评估索拉非尼在临床试验之外治疗患者的反应和无进展生存期（PFS）。次要终点是评估毒性谱。由于一名患者在开始索拉非尼一周后出现严重过敏皮疹，故排除了这一名患者。
该分析包括 12 名转移性 MTC 患者（中位年龄 48 岁），其中 10 名患有散发性疾病，2 名患有遗传性疾病。中位治疗时间为 11 个月，中位随访时间为 15.5 个月。在数据截止时，12 名患者中有 2 名（16%）仍在接受治疗，时间分别为 16 个月和 34 个月。根据实体瘤反应评估标准，10 名（83.3%）患者的疾病稳定，2 名（16.6%）患者的疾病进展；未观察到部分缓解。中位 PFS 为 9 个月。然而，3 名广泛且快速进展的疾病患者在接受索拉非尼治疗后 3 个月内死亡。排除这 3 名患者后，中位 PFS 为 12 个月。9 名（75%）患者发生不良事件（AE）。主要的 AE 是皮肤毒性、体重减轻和疲劳。5 名（41.6%）患者需要减少剂量，1 名患者因毒性而停止治疗。
在进展性转移性 MTC 中使用索拉非尼治疗耐受性良好，75%的患者疾病得到控制并获得持久的临床获益。当凡德他尼和卡博替尼不可用时或在这些药物治疗失败后，可考虑使用索拉非尼治疗。
