Phase I trial of axitinib combined with platinum doublets in patients with advanced non-small cell lung cancer and other solid tumours.
Phase I trial of axitinib combined with platinum doublets in patients with advanced non-small cell lung cancer and other solid tumours.
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DOI：
10.1038/bjc.2012.406
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发表时间：
2012-10-09
影响因子：
8.8
通讯作者：
Cohen, R. B.
中科院分区：
文献类型：
--
作者：
Kozloff, M. F.;Martin, L. P.;Krzakowski, M.;Samuel, T. A.;Rado, T. A.;Arriola, E.;De Castro Carpeno, J.;Herbst, R. S.;Tarazi, J.;Kim, S.;Rosbrook, B.;Tortorici, M.;Olszanski, A. J.;Cohen, R. B.
这项I期剂量发现试验评估了阿西替尼的安全性、有效性和药代动力学，阿西替尼是一种有效的、选择性的第二代血管内皮生长因子受体抑制剂，联合铂双药治疗晚期非小细胞肺癌（NSCLC）和其他实体肿瘤患者。总共有49名患者接受阿西替尼5mg，每日2次，与紫杉醇/卡铂或吉西他滨/顺铂联合治疗，周期为3周。在确定最大耐受剂量后，纳入了一个鳞状细胞NSCLC扩展队列，并接受阿西替尼5mg b.d联合紫杉醇/卡铂治疗。2例患者出现剂量限制性毒性：紫杉醇/卡铂组发热性中性粒细胞减少（n=1），吉西他滨/顺铂组疲劳（n=1）。常见的非血液学治疗相关不良事件是高血压（36.7%）、腹泻（34.7%）和疲劳（28.6%）。在12名鳞状细胞NSCLC患者中没有发生小于3级的咯血。阿西替尼/紫杉醇/卡铂组患者客观缓解率为37.0% (n=27)，阿西替尼/吉西他滨/顺铂组患者客观缓解率为23.8% （n=21）。阿西替尼和化疗药物的药代动力学在单独或联合使用时相似。阿西替尼5mg b.d可与标准紫杉醇/卡铂或吉西他滨/顺铂方案联合使用，没有明显的药物-药物相互作用的证据。两种组合均表现出临床疗效和良好的耐受性。
This phase I dose-finding trial evaluated safety, efficacy and pharmacokinetics of axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors, combined with platinum doublets in patients with advanced non-small cell lung cancer (NSCLC) and other solid tumours. In all, 49 patients received axitinib 5 mg twice daily (b.i.d.) with paclitaxel/carboplatin or gemcitabine/cisplatin in 3-week cycles. Following determination of the maximum tolerated dose, a squamous cell NSCLC expansion cohort was enroled and received axitinib 5 mg b.i.d. with paclitaxel/carboplatin. Two patients experienced dose-limiting toxicities: febrile neutropenia (n=1) in the paclitaxel/carboplatin cohort and fatigue (n=1) in the gemcitabine/cisplatin cohort. Common nonhaematologic treatment-related adverse events were hypertension (36.7%), diarrhoea (34.7%) and fatigue (28.6%). No grade⩾3 haemoptysis occurred among 12 patients with squamous cell NSCLC. The objective response rate was 37.0% for patients receiving axitinib/paclitaxel/carboplatin (n=27) and 23.8% for patients receiving axitinib/gemcitabine/cisplatin (n=21). Pharmacokinetics of axitinib and chemotherapeutic agents were similar when administered alone or in combination. Axitinib 5 mg b.i.d. may be combined with standard paclitaxel/carboplatin or gemcitabine/cisplatin regimens without evidence of overt drug–drug interactions. Both combinations demonstrated clinical efficacy and were well tolerated.
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DOI：
10.1200/jco.2007.15.9566
发表时间：
2008-10-10
期刊：
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
影响因子：
--
作者：
Cohen EE;Rosen LS;Vokes EE;Kies MS;Forastiere AA;Worden FP;Kane MA;Sherman E;Kim S;Bycott P;Tortorici M;Shalinsky DR;Liau KF;Cohen RB
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DOI：
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发表时间：
2010-09
期刊：
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影响因子：
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通讯作者：
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影响因子：
45.3
作者：
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通讯作者：
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影响因子：
158.5
作者：
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影响因子：
45.3
作者：
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通讯作者：
Dutcher, Janice P.