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BJC:新型联合疗法可有效抑制耐受性肉瘤的生长

来源:生物谷 2014-07-13 11:29

2014年7月13日 讯 /生物谷BIOON/ --近日,来自Bellvitge生物医学研究所等处的研究人员通过一种新型的结合治疗手段对19位患者进行耐受性肉瘤的研究诊断,结果显示,这种新型疗法可以有效缓解耐受性肉瘤的生长,相关研究成果刊登于国际杂志British Journal of Cancer上。

肉瘤是一种罕见类型复杂肿瘤,其有许多亚型,可以影响儿童至老年人任何年龄段的个体,文章中,研究者利用不同种传统化疗的方法同新型药物相结合,在分子靶向水平上对细胞肉瘤进行研究,科学家们利用雷帕霉素和治疗肉瘤的常用化疗方法相结合来对小鼠进行试验,雷帕霉素是在mTOR路径中较为特殊的一种药物,而mTOR则是许多类型癌症中的关键蛋白质。

研究者Martinez-Tirado表示,利用细胞系进行研究,我们发现,这种新型结合疗法可以明显阻断小鼠机体中汇总刘的生长,如果单独利用雷帕霉素或一般化疗方法所得到的效果并不如结合疗法明显;目前研究人员正在进行I期临床试验,研究者在19位病人中检测这种新型结合疗法的效果,尽管I期临床试验用于确定合适可推荐的药物剂量以及排除药物的毒性,但是研究者的确发现这种结合疗法在治疗不同类型的肉瘤上表现出了较好的效果。

基于I期临床试验的可喜结果,研究者目前已经开启了II期临床试验,并且已经对病人进行了招募,研究者后期将会检测是否这种联合疗法的确可以在这些患者中发挥明显作用以及是否这种新型疗法效果要优于当前的其它疗法。(生物谷Bioon.com)

Phase I study and preclinical efficacy evaluation of the mTOR inhibitor sirolimus plus gemcitabine in patients with advanced solid tumours

J Martin-Liberal, M Gil-Martín, M Sáinz-Jaspeado, N Gonzalo, R Rigo, H Colom, C Muñoz, O M Tirado and X García del Muro

Background: We conducted a phase I study in patients with advanced solid tumours to identify the recommended dose, assess pharmacokinetics (PK), pharmacodynamic activity and preclinical antitumour efficacy of the combination of sirolimus and gemcitabine. Methods: Nineteen patients were treated with sirolimus 2 or 5 mg daily and gemcitabine 800 or 1000 mg m−2 on days 1 and 8. Dose escalation depended on dose-limiting toxicity (DLT) rate during the first 3-week period. Paired skin biopsies were evaluated for phosphorylated S6 (pS6) as marker of mTOR (mammalian target of rapamycin) inhibition. Pharmacokinetics and preclinical evaluation of efficacy using two different sarcoma cell lines and leiomyosarcoma xenografts were also conducted. Results: Three DLTs were observed: grade 3 transaminitis, grade 3 thrombocytopenia and grade 4 thrombocytopenia. Common treatment-related adverse events included anaemia, neutropenia, thrombocytopenia and transaminitis. Pharmacodynamic analyses demonstrated mTOR inhibition with sirolimus 5 mg and PK showed no influence of sirolimus concentrations on gemcitabine clearance. In vitro and in vivo studies suggested mTOR pathway hyperactivation by gemcitabine that was reversed by sirolimus. Tumour growth in leiomyosarcoma xenografts was dramatically inhibited by the treatment. Conclusions: Recommended dose was sirolimus 5 mg per 24 h plus gemcitabine 800 mg m−2. Antitumour activity in preclinical sarcoma models and mTOR signalling inhibition were observed. A phase II study is currently ongoing.

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