Open-label feasibility study of pazopanib, carboplatin, and paclitaxel in women with newly diagnosed, untreated, gynaecologic tumours: a phase I/II trial of the AGO study group

被引:18
作者
du Bois, A. [1 ,2 ]
Vergote, I. [3 ]
Wimberger, P. [4 ]
Ray-Coquard, I. [5 ]
Harter, P. [1 ,2 ]
Curtis, L. B. [6 ]
Mitrica, I. [7 ]
机构
[1] Kliniken Essen Mitte, Dept Gynecol, D-45136 Essen, Germany
[2] Kliniken Essen Mitte, Dept Gynecol Oncol, D-45136 Essen, Germany
[3] Katholieke Univ Leuven Hosp, Dept Gynecol Oncol, Louvain, Belgium
[4] Univ Duisburg Essen, Dept Gynecol & Obstet, Essen, Germany
[5] Ctr Leon Berard, F-69373 Lyon, France
[6] GlaxoSmithKline, London, England
[7] GlaxoSmithKline, Res Triangle Pk, NC USA
关键词
ovarian cancer; pazopanib; phase I study; RECURRENT; COMBINATION; MONOTHERAPY; BEVACIZUMAB; CARCINOMA; THERAPY;
D O I
10.1038/bjc.2011.608
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
INTRODUCTION: Although most patients with advanced gynaecologic malignancies respond to first-line treatment with platinum-taxane doublets, a significant proportion of patients relapse. Combining targeted agents that have non-overlapping mechanisms of action with chemotherapy may potentially increase the disease-free interval. Accordingly, this study evaluated the feasibility of combining pazopanib, an oral angiogenesis inhibitor, with paclitaxel and carboplatin. METHODS: This open-label, phase I/II study planned to evaluate the safety and efficacy of paclitaxel 175 mg m(-2) plus carboplatin (AUC5 (Arm A) or AUC6 (Arm B)) once in every 3 weeks for up to six cycles with either 800 or 400 mg per day pazopanib. RESULTS: Dose-limiting toxicities (DLTs) were observed in two of the first six patients enrolled at pazopanib 800 mg plus paclitaxel 175 mg m(-2) plus carboplatin AUC5. Of the six patients enrolled in the next and lowest dosing level planned in the study, pazopanib 400 mg plus paclitaxel 175 mg m(-2) plus carboplatin AUC5, two patients also experienced DLTs and the study was terminated. Two of the 4 DLTs observed overall were gastrointestinal perforations. Severe myelotoxicity was reported in 6 of 12 patients. CONCLUSION: Combining either 800 or 400 mg per day pazopanib with standard carboplatin/paclitaxel chemotherapy is not a feasible treatment option.
引用
收藏
页码:629 / 632
页数:4
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