Phase I Trial of Intrapleural Docetaxel Administered Through an Implantable Catheter in Subjects with a Malignant Pleural Effusion
Phase I Trial of Intrapleural Docetaxel Administered Through an Implantable Catheter in Subjects with a Malignant Pleural Effusion
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DOI：
10.1097/jto.0b013e3181c07ddc
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发表时间：
2010-01-01
影响因子：
20.4
通讯作者：
Gillenwater, Heidi H.
中科院分区：
文献类型：
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作者：
Jones, David R.;Taylor, Matthew D.;Gillenwater, Heidi H.
前言：恶性胸腔积液（MPE）是晚期恶性肿瘤患者的常见并发症。这项剂量递增I期研究旨在确定MPE受试者通过植入式导管胸膜内给予多西他赛的最大耐受剂量。MPE受试者（n = 15）中位年龄为64.6岁，基线时东部肿瘤协作组体力状态为0 - 2，入选4个单剂量水平的多西他赛，在引流后胸膜内给药。胸腔积液和插入胸腔内导管。本研究测定了胸膜内多西他赛的药代动力学特性、临床反应和毒性特征。结果：所有患者均耐受良好，无明显毒性反应。大多数患者的放射学反应完全。所有接受100 mg/m2或更高剂量的患者都有完全的放射学反应。在剂量50 mg/m2时出现一种剂量限制性毒性。药代动力学数据显示多西他赛的血浆峰浓度在输注后30分钟至6小时之间。胸膜接触多西他赛是1000倍高于systemic exposure.Conclusions：单剂量的多塞鲁肽胸膜内给药是耐受性良好的MPE患者毒性最小。在本研究中，胸膜内注射多西他赛治疗后的良好临床反应表明需要进一步研究。
Introduction: Malignant pleural effusion (MPE) is a common complication in patients with advanced malignancy. This dose escalation phase I study was designed to determine the maximum tolerated dose of intrapleural docetaxel administered through an implantable catheter in subjects with MPE.Methods: Subjects with MPE (n = 15) with median age of 64.6 years and an Eastern Cooperative Oncology Group performance status of 0 to 2 at baseline were enrolled into four single dose levels of docetaxel administered intrapleurally after drainage of the pleural effusion and insertion of an intrapleural catheter. The study determined the pharmacokinetic properties, clinical response, and toxicity profile of intrapleural docetaxel.Results: All patients tolerated the therapy well and there were no significant toxicities. The majority of patients had a complete radiographic response. All patients receiving dose 100 mg/m(2) or higher had a complete radiographic response. One dose-limiting toxicity was encountered in the dose 50 mg/m(2). Pharmacokinetic data demonstrated peak plasma concentration of docetaxel between 30 minutes and 6 hours after infusion. Pleural exposure to docetaxel was 1000 times higher than systemic exposure.Conclusions: Single-dose intrapleural administration of doxetaxel is well tolerated in patients with MPE with minimal toxicity. The excellent clinical responses in this study after treatment with intrapleural doxetaxel suggest that further investigation is warranted.