Safety and pharmacokinetics of paclitaxel and the oral mTOR inhibitor everolimus in advanced solid tumours.
Safety and pharmacokinetics of paclitaxel and the oral mTOR inhibitor everolimus in advanced solid tumours.
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DOI：
10.1038/sj.bjc.6604851
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发表时间：
2009-01-27
影响因子：
8.8
通讯作者：
Raymond, E.
中科院分区：
文献类型：
--
作者：
Campone, M.;Levy, V.;Bourbouloux, E.;Rigaud, D. Berton;Bootle, D.;Dutreix, C.;Zoellner, U.;Shand, N.;Calvo, F.;Raymond, E.
依维莫司显示出对癌细胞的抗增殖作用，在已建立的肿瘤中产生抗血管生成活性，并在临床前模型中显示出与紫杉醇的协同作用。本研究评估了依维莫司和紫杉醇在晚期恶性肿瘤患者中的安全性和药代动力学相互作用。依维莫司的剂量从15 mg增加到30 mg，并在第1、8和15天每28天与紫杉醇80 mg m - 2一起施用。每周评估安全性，并在第1周期评估剂量限制性毒性（DLT）。共纳入16例患者（中位年龄54.5岁，范围33-69岁）；11例既往紫杉烷治疗过乳腺癌（n=5）、卵巢癌（n=3）和阴道癌（n=1）或血管肉瘤（n=2）。6例3级中性粒细胞减少患者符合DLT标准，2例接受依维莫司每周30mg。其他与药物相关的3级毒性包括白细胞减少、贫血、血小板减少、口炎、虚弱和肝酶升高。11例乳腺癌患者中2例肿瘤稳定超过6个月。Everolimus在30 mg剂量下与每周80 mg紫杉醇联合使用时显示出可接受的安全性，值得进一步的临床研究。
Everolimus displays antiproliferative effects on cancer cells, yields antiangiogenic activity in established tumours, and shows synergistic activity with paclitaxel in preclinical models. This study assessed the safety and the pharmacokinetic interactions of everolimus and paclitaxel in patients with advanced malignancies. Everolimus was dose escalated from 15 to 30 mg and administered with paclitaxel 80 mg m−2 on days 1, 8, and 15 every 28 days. Safety was assessed weekly, and dose-limiting toxicity (DLT) was evaluated in cycle 1. A total of 16 patients (median age 54.5 years, range 33–69) were entered; 11 had prior taxane therapy for breast (n=5), ovarian (n=3), and vaginal cancer (n=1) or angiosarcoma (n=2). Grade 3 neutropenia in six patients met the criteria for DLT in two patients receiving everolimus 30 mg weekly. Other drug-related grade 3 toxicities were leucopenia, anaemia, thrombocytopenia, stomatitis, asthenia, and increased liver enzymes. Tumour stabilisation reported in 11 patients exceeded 6 months in 2 patients with breast cancer. Everolimus showed an acceptable safety profile at the dose of 30 mg when combined with weekly paclitaxel 80 mg m−2, warranting further clinical investigation.
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影响因子：
8.8
作者：
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通讯作者：
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45.3
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