Weekly AUC2 carboplatin in acquired platinum resistant ovarian cancer with or without oral phenoxodiol, a sensitizer of platinum cytotoxicity: the phase Ill OVATURE multicenter randomized study
Weekly AUC2 carboplatin in acquired platinum resistant ovarian cancer with or without oral phenoxodiol, a sensitizer of platinum cytotoxicity: the phase Ill OVATURE multicenter randomized study
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DOI：
10.1093/annonc/mdt515
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发表时间：
2014-01-01
影响因子：
50.5
通讯作者：
Gabra, H.
中科院分区：
文献类型：
--
作者：
Fotopoulou, C.;Vergote, I.;Gabra, H.
背景：耐铂卵巢癌(Proc)与传统的细胞毒药相比疗效有限，是一种治疗难题。基于先前的数据表明改变铂的时间安排会增加活动性，本研究的目的是评估一种新的生物调节剂苯氧二醇(PXD)在每周联合AUC2-卡铂时对PROC患者的潜在治疗益处。患者和方法：采用多中心随机双盲安慰剂对照III期研究，比较口服PXD加AUC2-卡铂(组1)和安慰剂+AUC2-卡铂(组2)每周对PROC患者的疗效。主要终点是无进展生存(PFS)。次要目标包括总生存期(OS)、应答率、应答期和生活质量。结果：由于可行性和招募挑战，该研究于2009年4月14日初终止，招募了142名患者。共有142名患者被随机分组。就重要的基线特征而言，这些群体的平衡程度很好。第1组的中位PFS为15.4周[95%可信区间11.1-21.0]，第2组为20.1周(95%可信区间13.1-33.4)；P0.3。第1组和第2组的客观缓解率和中位生存期分别为0%和1%和38.3周(95%可信区间32.0~45.3)和45.7周(95%可信区间35.6~58.0)。PXD似乎耐受性良好。两组剂量调整的主要原因是血液毒性。结论：口服PXD与每周一次的AUC2-卡铂联合应用无临床活性。此外，根据反应标准，每周单剂AUC2-卡铂在同质定义的proc人群中似乎是无效的。这对未来研究的设计有一定的影响。
Background: Platinum-resistant ovarian cancer (PROC) constitutes a therapeutic dilemma with limited efficacy from traditional cytotoxic agents. Based on prior data suggesting that scheduling alterations of platinum would increase activity, the aim of the present study was to assess the potential therapeutic benefit of phenoxodiol (PXD), a novel biomodulator shown to have chemoresistance reversing potential, when combined with weekly AUC2-carboplatin in PROC patients.Patients and methods: A multicenter randomized double-blind placebo controlled phase-III-study was conducted to compare oral PXD plus AUC2-carboplatin (group 1) versus placebo plus AUC2-carboplatin (group 2) weekly in PROC patients. The primary end point was progression-free-survival (PFS). Secondary objectives included overall survival (OS), response rates, duration of response and quality of life.Results: The study was terminated early 14 April 2009, after recruitment of 142 patients due to feasibility and recruitment challenges. A total of 142 patients were randomized. The groups were well balanced in terms of important baseline characteristics. The median PFS for group 1 was 15.4 weeks [95% confidence interval (Cl) 11.1-21.0] versus 20.1 weeks for group 2 (95% Cl 13.1-33.4); P 0.3. The objective response rate and median survival in group 1 versus group 2 was 0% versus 1% and 38.3 weeks (95% Cl 32.0-45.3) versus 45.7 weeks (95% Cl 35.6-58.0), respectively. PXD appeared to be well tolerated. The main reason for dose modification in both groups was hematologic toxicity.Conclusions: Orally delivered PXD showed no evidence of clinical activity, when combined with weekly AUC2-carboplatin in PROC. In addition, single-agent weekly AUC2-carboplatin appeared to be inactive by response criteria in a homogenously defined population of PROC. This has implications for the design of future studies.Clinicaltrials.gov identifier: NCT00382811.