司美替尼（Selumetinib）（结构式见下图）是一种小分子MEK抑制剂，关于其用于癌症治疗已经有不少报道，如司美替尼联合多西紫杉醇治疗：KARS突变的晚期非小细胞肺癌 ； 司美替尼治疗转移性胆道癌耐受性尚可；司美替尼单药治疗肝细胞癌效果甚微；窥一斑而探全豹，观滴水可测沧海 2012 ASCO临床肿瘤学进展盘点；司美替尼对复发的卵巢低分化鳞癌有效等，但是2013年2月8日《科学日报》（ScienceDaily）网站报道了美国德克萨斯大学MD安德森癌症中心（The University of Texas MD Anderson Cancer Center）的最新研究成果发现，司美替尼对于低级浆液性卵巢癌有一定的治疗效果。

图1 司美替尼（Selumetinib）结构式

低级浆液性卵巢癌是不太常见的侵略性的一种癌症，当前线治疗失败时，非常难治。就是手术之后，无论有还是没有预先化疗，低级浆液性卵巢癌的复发率很高,化疗和激素治疗是相对无效的。治疗应答率是以个位数来衡量。美国德克萨斯大学MD安德森癌症中心，妇科肿瘤学和生殖医学系教授David Gershenson医学博士以及他的研究团队，在过去20年一直在关注低级浆液性卵巢癌疾病的研究，并寻找新的治疗方法，因为这种疾病占卵巢癌病例的10%。就是治疗之后复发或者持续比例在80%到85%之间。但是司美替尼可以阻止肿瘤增长或者使肿瘤缩小。在第一次对低级浆液性卵巢癌有针对性疗法的临床试验（2007年12月17日到2009年11月23日）中,52例低级浆液性卵巢癌患者中有8例(占15%)出现肿瘤收缩，有34例(占65%)在两年之内尚未发现疾病有所进展。相关研究结果刊登在2月出版的《柳叶刀肿瘤学》（The Lancet Oncology）杂志上，更多信息请浏览：

The Lancet Oncology, Volume 14, Issue 2, Pages 134 - 140, February 2013

doi:10.1016/S1470-2045(12)70572-7 Cite or Link Using DOI

Published Online: 21 December 2012

Original Text

Prof John Farley MD a , William E Brady PhD b, Vinod Vathipadiekal PhD c, Heather A Lankes PhD b, Prof Robert Coleman MD d, Prof Mark A Morgan MD e, Prof Robert Mannel MD f, Prof S Diane Yamada MD g, Prof David Mutch MD h, Prof William H Rodgers MD i, Michael Birrer MD c, David M Gershenson MD d

Background

Low-grade serous carcinoma of the ovary is chemoresistant but mutations in the MAPK pathway could be targeted to control tumour growth. We therefore assessed the safety and activity of selumetinib, an inhibitor of MEK1/2, for patients with this cancer.

Methods

In this open-label, single-arm phase 2 study, women (aged ≥18 years) with recurrent low-grade serous ovarian or peritoneal carcinoma were given selumetinib (50 mg twice daily, orally) until progression. The primary endpoint was the proportion of patients who had an objective tumour response according to RECIST version 1.1, assessed for all the treated patients. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00551070.

Findings

52 patients were enrolled between Dec 17, 2007, and Nov 23, 2009. All were eligible for analyses. Eight (15%) patients had an objective response to treatment—one patient had a complete response and seven had partial responses. 34 (65%) patients had stable disease. There were no treatment-related deaths. Grade 4 toxicities were cardiac (one), pain (one), and pulmonary events (one). Grade 3 toxicities that occurred in more than one patient were gastrointestinal (13), dermatological (nine), metabolic (seven), fatigue (six), anaemia (four), pain (four), constitutional (three), and cardiac events (two).

Interpretation

Selumetinib is well tolerated, and is active in the treatment of recurrent low-grade serous carcinoma of the ovary or peritoneum. The findings suggest that inhibitors of the MAPK pathway warrant further investigation in these patients.