A Phase II, randomized, double-blind study of zibotentan (ZD4054) in combination with carboplatin/paclitaxel versus placebo in combination with carboplatin/paclitaxel in patients with advanced ovarian cancer sensitive to platinum-based chemotherapy (AGO-OVAR 2.14)

被引：21

作者：

Cognetti, F. ^{[1
]}

Bagnato, A. ^{[1
]}

Colombo, N. ^{[2
]}

Savarese, A. ^{[1
]}

Scambia, G. ^{[3
]}

Sehouli, J. ^{[4
]}

Wimberger, P. ^{[5
]}

Sorio, R. ^{[6
]}

Harter, P. ^{[7
]}

Mari, E. ^{[8
]}

McIntosh, S. ^{[9
]}

Nathan, F. ^{[10
]}

Pemberton, K. ^{[9
]}

Baumann, K. ^{[11
]}

机构：

[1] Regina Elena Inst Canc Res, I-00144 Rome, Italy

[2] Univ Milano Bicocca, European Inst Oncol, Med Gynecol Oncol Unit, Milan, Italy

[3] Univ Cattolica Sacro Cuore, I-00168 Rome, Italy

[4] Charite Univ Med Berlin, Berlin, Germany

[5] Univ Duisburg Essen, Essen, Germany

[6] Ctr Riferimento Oncol, Aviano, Italy

[7] Kliniken Essen Mitte, Essen, Germany

[8] AstraZeneca, Basiglio, Italy

[9] AstraZeneca, Macclesfield, Cheshire, England

[10] AstraZeneca, Wilmington, DE USA

[11] Univ Giessen Klinikum & Marburg GmbH, Marburg, Germany

来源：

GYNECOLOGIC ONCOLOGY | 2013年 / 130卷 / 01期

关键词：

Zibotentan; ZD4054; Carboplatin/paclitaxel; Advanced; Ovarian; Cancer; GROWTH-FACTOR RECEPTOR; ENDOTHELIN AXIS; PACLITAXEL; THERAPY; BEVACIZUMAB; ANTAGONIST; TRIAL;

D O I：

10.1016/j.ygyno.2012.12.004

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Background. In platinum-sensitive relapsed ovarian cancer, paclitaxel plus carboplatin is a standard secondline treatment. Zibotentan (ZD4054) is an oral, specific ETA-receptor antagonist with demonstrated antitumour activity in xenograft models of human ovarian cancer. Methods. In this Phase II, randomized, placebo-controlled study, patients with relapsed ovarian cancer sensitive to platinum-based chemotherapy received zibotentab 10 mg or placebo once-daily, plus paclitaxel 175 mg/m(2) iv followed by carboplatin iv (AUC 5) on day 1 of every 3-week cycle for a maximum of eight cycles. The primary endpoint was progression-free survival (PFS), evaluated by Response Evaluation Criteria In Solid Tumours (RECIST). Secondary and exploratory endpoints included objective tumour response rate, tumour size, CA-125/RECIST progression, and safety and tolerability. Results. A total of 120 patients were randomized (zibotentan: n=59; placebo: n=61). Addition of zibotentan 10 mg/day to carboplatin and paclitaxel did not improve PFS compared with placebo (median PFS, 7.6 versus 10.0 months, respectively; HR=1.46, [80% CI: 1.10-1.94]; P=0.0870). No improvements in any of the secondary or exploratory efficacy endpoints were observed for patients receiving zibotentan compared with placebo. Median duration of total treatment exposure was 6.7 months. Total chemotherapy dose received was lower for zibotentan-treated versus placebo-treated patients (carboplatin: -16%; paclitaxel: -14%). The most common adverse events in the zibotentan arm were anaemia, nausea, alopecia, headache and neutropenia (43-48% of patients). Conclusions. Zibotentan 10 mg/day plus carboplatin and paclitaxel did not result in an improvement in PFS compared with chemotherapy alone in patients with advanced ovarian cancer sensitive to platinum-based chemotherapy. No unexpected safety concerns were identified. (C) 2012 Published by Elsevier Inc.

引用

页码：31 / 37

页数：7

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