Nassif Elise, Thibault Constance, Vano Yann, Fournier Laure, Mauge Laetitia, Verkarre Virginie, Timsit Marc-Olivier, Mejean Arnaud, Tartour Eric, Oudard Stéphane
a Oncology Department , Georges Pompidou European Hospital , Paris , France.
g Université Paris Descartes Sorbonne Paris-Cité , Paris 5 , France.
Expert Rev Anticancer Ther. 2017 Feb;17(2):129-142. doi: 10.1080/14737140.2017.1272415. Epub 2016 Dec 27.
Sunitinib is a multi-target, anti-angiogenic tyrosine kinase inhibitor and a key molecule in the treatment of metastatic renal cell carcinoma (mRCC). Since it first demonstrated its efficacy ten years ago, overall survival of mRCC has more than doubled, in part due to sunitinib. In most recent years, progress has been made in the comprehension of its mechanism of action and resistance. Areas Covered: In this article, clinical trials involving sunitinib in kidney cancer have been reviewed, defining its different indications in metastatic and localized RCC. The rationale of sunitinib's efficacy, preclinical trials, past-clinical trials and ongoing clinical trials are summarized. Dose and scheme base are discussed, as the recommended dosage is frequently not well tolerated. Combination therapies appear to be toxic. Novel immunotherapies are changing the landscape of mRCC treatment and challenging sunitinib. Special attention has been paid towards cancer cell biology and immunity involved in treatment response. Expert Commentary: Sunitinib's place in the therapeutic arsenal is being redefined with the arrival of major challengers. Dosage and scheduling of sunitinib remains a major challenge.
舒尼替尼是一种多靶点抗血管生成酪氨酸激酶抑制剂,是治疗转移性肾细胞癌(mRCC)的关键分子。自十年前首次证明其疗效以来,mRCC患者的总生存期增加了一倍多,部分归功于舒尼替尼。近年来,在理解其作用机制和耐药性方面取得了进展。涵盖领域:本文回顾了舒尼替尼用于肾癌的临床试验,明确了其在转移性和局限性肾细胞癌中的不同适应证。总结了舒尼替尼疗效的理论依据、临床前试验、既往临床试验和正在进行的临床试验。讨论了剂量和方案基础,因为推荐剂量往往耐受性不佳。联合疗法似乎具有毒性。新型免疫疗法正在改变mRCC的治疗格局并对舒尼替尼构成挑战。特别关注了参与治疗反应的癌细胞生物学和免疫情况。专家评论:随着主要挑战者的出现,舒尼替尼在治疗武器库中的地位正在被重新定义。舒尼替尼的剂量和给药方案仍然是一个重大挑战。