Randomised phase II study of ASA404 combined with carboplatin and paclitaxel in previously untreated advanced non-small cell lung cancer.
Randomised phase II study of ASA404 combined with carboplatin and paclitaxel in previously untreated advanced non-small cell lung cancer.
复制标题
DOI：
10.1038/sj.bjc.6604808
复制
发表时间：
2008-12-16
影响因子：
8.8
通讯作者：
Quoix, E.
中科院分区：
文献类型：
--
作者：
McKeage, M. J.;Von Pawel, J.;Reck, M.;Jameson, M. B.;Rosenthal, M. A.;Sullivan, R.;Gibbs, D.;Mainwaring, P. N.;Serke, M.;Lafitte, J-J;Chouaid, C.;Freitag, L.;Quoix, E.
ASA 404（5，6-二甲基咕吨酮-4-乙酸或DMXAA）是一种小分子肿瘤血管破坏剂（肿瘤-VDA）。这项随机化II期研究评价了ASA 404加卡铂和紫杉醇标准治疗在既往未接受过化疗的经组织学证实的IIIb或IV期非小细胞肺癌（NSCLC）患者中的疗效。患者被随机分配接受106个周期的卡铂血药浓度-时间曲线下面积6 mg ml−1 min和紫杉醇175 mg m−2（CP，n=36）或标准治疗加ASA 404 1200 mg m−2（ASA 404-CP，n=37）。加入ASA 404后，总或游离卡铂或紫杉醇的全身暴露量几乎没有变化。两组的安全性特征相似且易于管理，大多数不良反应归因于标准治疗。与标准治疗组相比，ASA 404联合治疗组的肿瘤缓解率（31 vs 22%）、至肿瘤进展的中位时间（5.4 vs 4.4个月）和中位生存期（14.0 vs 8.8个月，风险比0.73，95% CI 0.39，1.38）均有所改善。总之，本研究确定了ASA 404与卡铂和紫杉醇联合治疗既往未经治疗的晚期NSCLC患者的可行性，证明了可管理的安全性特征，并且没有不良的药代动力学相互作用。结果表明，ASA 404可能有益处，但这需要在更大规模的试验中进行评估。
ASA404 (5,6-dimethylxanthenone-4-acetic acid or DMXAA) is a small-molecule tumour-vascular disrupting agent (Tumour-VDA). This randomised phase II study evaluated ASA404 plus standard therapy of carboplatin and paclitaxel in patients with histologically confirmed stage IIIb or IV non-small cell lung cancer (NSCLC) not previously treated with chemotherapy. Patients were randomised to receive ⩽6 cycles of carboplatin area under the plasma concentration–time curve 6 mg ml−1 min and paclitaxel 175 mg m−2 (CP, n=36) or standard therapy plus ASA404 1200 mg m−2 (ASA404-CP, n=37). There was little change in the systemic exposure of either total or free carboplatin or paclitaxel on addition of ASA404. Safety profiles were similar and manageable in both groups, with most adverse effects attributed to standard therapy. Tumour response rate (31 vs 22%), median time to tumour progression (5.4 vs 4.4 months) and median survival (14.0 vs 8.8 months, hazard ratio 0.73, 95% CI 0.39, 1.38) were improved in the ASA404 combination group compared with the standard therapy group. In conclusion, this study establishes the feasibility of combining ASA404 with carboplatin and paclitaxel in patients with previously untreated, advanced NSCLC, demonstrating a manageable safety profile and lack of adverse pharmacokinetic interactions. The results indicate that there may be a benefit associated with ASA404, but this needs to be evaluated in a larger trial.
登录
查看更多内容
影响因子：
45.3
作者：
LANGER, CJ;LEIGHTON, JC;OZOLS, RF
通讯作者：
OZOLS, RF
影响因子：
158.5
作者：
Sandler, Alan;Gray, Robert;Johnson, David H.
通讯作者：
Johnson, David H.
5,6-二甲基苯乙烯-4-乙酸（DMXAA），一种新型的抗血管剂：I期临床和药代动力学研究。
影响因子：
8.8
作者：
通讯作者：
--
抗血管剂5,6-二甲基苯乙烯-4-乙酸诱导内皮细胞凋亡。
影响因子：
8.8
作者：
Ching, LM;Cao, Z;Kieda, C;Zwain, S;Jameson, MB;Baguley, BC
通讯作者：
Baguley, BC
影响因子：
8.8
作者：
通讯作者：
--