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索拉非尼治疗甲状腺癌:最新综述

Sorafenib for the treatment of thyroid cancer: an updated review.

作者信息

Krajewska Jolanta, Handkiewicz-Junak Daria, Jarzab Barbara

机构信息

Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Nuclear Medicine and Endocrine Oncology Department, Gliwice Branch , Gliwice , Poland + 48 32 2789301 ; +48 32 2789310 ;

出版信息

Expert Opin Pharmacother. 2015 Mar;16(4):573-83. doi: 10.1517/14656566.2015.1005601. Epub 2015 Jan 21.

Abstract

INTRODUCTION

Sorafenib (Nexavar) is an oral multi-kinase inhibitor targeting B-type Raf kinase (BRAF) (both wild type and BRAF(V600E)), VEGFR1, VEGFR2, VEGFR3, PDGFRβ and RET (also RET/PTC) influencing both differentiated thyroid cancer (DTC) cell proliferation and angiogenesis.

AREAS COVERED

Encouraging results achieved in numerous Phase II trials were confirmed in a Phase III study conducted in radioiodine-refractory DTC. Sorafenib compared to placebo significantly prolongs progression-free survival, 10.8 versus 5.8 months, respectively. However, its administration resulted mainly in disease stabilization. No complete remission was obtained in any study. Beneficial effects were also demonstrated for medullary and anaplastic thyroid cancer; however further studies fulfilling evidence based medicine criteria are necessary. Its toxicity profile is convergent with other VEGFR inhibitors. The most common treatment-related side-effects involve skin toxicity (predominantly hand-foot skin reaction, different rashes and alopecia), gastrointestinal disturbances (diarrhea, abdominal pain), constitutional adverse reactions (anorexia, weight loss, fatigue) and hypertension. Although most adverse reactions are manageable, > 50% of patients required dose reduction.

EXPERT OPINION

Sorafenib constitutes the first line treatment option in advanced, radioiodine-refractory DTC. However, there are still no data on its efficacy in patients progressed after another tyrosine kinase inhibitor. Other applications of the drug, such as use as adjuvant therapy to 131-I treatment, requires further studies.

摘要

引言

索拉非尼(多吉美)是一种口服多激酶抑制剂,可靶向B型 Raf 激酶(BRAF)(野生型和BRAF(V600E))、血管内皮生长因子受体1(VEGFR1)、血管内皮生长因子受体2(VEGFR2)、血管内皮生长因子受体3(VEGFR3)、血小板衍生生长因子受体β(PDGFRβ)和RET(也包括RET/PTC),影响分化型甲状腺癌(DTC)细胞增殖和血管生成。

涵盖领域

在放射性碘难治性DTC的III期研究中证实了在众多II期试验中取得的令人鼓舞的结果。与安慰剂相比,索拉非尼显著延长了无进展生存期,分别为10.8个月和5.8个月。然而,其给药主要导致疾病稳定。在任何研究中均未获得完全缓解。对髓样甲状腺癌和间变性甲状腺癌也显示出有益效果;然而,需要进一步开展符合循证医学标准的研究。其毒性特征与其他VEGFR抑制剂相似。最常见的治疗相关副作用包括皮肤毒性(主要是手足皮肤反应、不同皮疹和脱发)、胃肠道紊乱(腹泻、腹痛)、全身性不良反应(厌食、体重减轻、疲劳)和高血压。尽管大多数不良反应是可控的,但超过50%的患者需要减少剂量。

专家观点

索拉非尼是晚期放射性碘难治性DTC的一线治疗选择。然而,对于在另一种酪氨酸激酶抑制剂治疗后进展的患者,仍没有关于其疗效的数据。该药物的其他应用,如用作131-I治疗的辅助治疗,需要进一步研究。

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