Bortezomib/docetaxel combination therapy in patients with anthracycline-pretreated advanced/metastatic breast cancer: a phase I/II dose-escalation study.
Bortezomib/docetaxel combination therapy in patients with anthracycline-pretreated advanced/metastatic breast cancer: a phase I/II dose-escalation study.
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DOI：
10.1038/sj.bjc.6604347
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发表时间：
2008-05-06
影响因子：
8.8
通讯作者：
Baselga J
中科院分区：
文献类型：
--
作者：
Awada A;Albanell J;Canney PA;Dirix LY;Gil T;Cardoso F;Gascon P;Piccart MJ;Baselga J
本研究的目的是确定硼替佐米联合多西他赛在蒽环类药物预治疗的晚期/转移性乳腺癌患者中的剂量限制性毒性（DLT）和最大耐受剂量（MTD）。48例患者接受了8个21天周期的多西他赛（第1天60-100 mg m−2）+硼替佐米（第1、4、8和11天1.0-1.5 mg m−2）。在一个患者亚组中进行药效学和药代动力学分析。5例患者发生DLT：3级骨痛（n=1）和发热性中性粒细胞减少症（n=4）。MTD为硼替佐米1.5 mg m−2+多西他赛75 mg m−2。所有48例患者的安全性和有效性均可评估。最常见的不良反应是腹泻、恶心、脱发、虚弱和呕吐。最常见的3/4级毒性为中性粒细胞减少（44%）、发热性中性粒细胞减少和腹泻（各19%）。总体患者反应率为29%。中位进展时间为5.4个月。在确认缓解的患者中，中位至缓解时间为1.3个月，中位缓解持续时间为3.2个月。在MTD时，应答率为38%。硼替佐米/多西他赛的药代动力学特征与单药数据相当。添加多西他赛似乎不影响硼替佐米对20 S蛋白酶体活性的抑制。在不同硼替佐米剂量水平下，几乎所有时间点的平均α-1酸性糖蛋白浓度均较基线升高。硼替佐米加多西他赛是蒽环类药物预处理的晚期/转移性乳腺癌的有效联合治疗。安全性特征是可管理的，并且与单个药物的副作用一致。
The aim of this study was to determine the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of bortezomib plus docetaxel in patients with anthracycline-pretreated advanced/metastatic breast cancer. Forty-eight patients received up to eight 21-day cycles of docetaxel (60–100 mg m−2 on day 1) plus bortezomib (1.0–1.5 mg m−2 on days 1, 4, 8, and 11). Pharmacodynamic and pharmacokinetic analyses were performed in a subset of patients. Five patients experienced DLTs: grade 3 bone pain (n=1) and febrile neutropenia (n=4). The MTD was bortezomib 1.5 mg m−2 plus docetaxel 75 mg m−2. All 48 patients were assessable for safety and efficacy. The most common adverse events were diarrhoea, nausea, alopecia, asthenia, and vomiting. The most common grade 3/4 toxicities were neutropenia (44%), and febrile neutropenia and diarrhoea (each 19%). Overall patient response rate was 29%. Median time to progression was 5.4 months. In patients with confirmed response, median time to response was 1.3 months and median duration of response was 3.2 months. At the MTD, response rate was 38%. Pharmacokinetic characteristics of bortezomib/docetaxel were comparable with single-agent data. Addition of docetaxel appeared not to affect bortezomib inhibition of 20S proteasome activity. Mean alpha-1 acid glycoprotein concentrations increased from baseline at nearly all time points across different bortezomib dose levels. Bortezomib plus docetaxel is an active combination for anthracycline-pretreated advanced/metastatic breast cancer. The safety profile is manageable and consistent with the side effects of the individual agents.
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影响因子：
11.8
作者：
Lenz, HJ
通讯作者：
Lenz, HJ
影响因子：
11.5
作者：
Dreicer, Robert;Petrylak, Daniel;Roth, Bruce
通讯作者：
Roth, Bruce
影响因子：
45.3
作者：
Blaney, SM;Bernstein, M;Adamson, PC
通讯作者：
Adamson, PC
影响因子：
45.3
作者：
Hamilton, AL;Eder, JP;Muggia, FM
通讯作者：
Muggia, FM
影响因子：
5.7
作者：
Codony-Servat, J;Tapia, MA;Albanell, J
通讯作者：
Albanell, J