Phase I trial of three-weekly Docetaxel, Carboplatin and oral lenalidomide (Revlimid®) in patients with advanced solid tumors
Phase I trial of three-weekly Docetaxel, Carboplatin and oral lenalidomide (Revlimid®) in patients with advanced solid tumors
复制标题
DOI：
10.1007/s10637-006-9025-4
复制
发表时间：
2007-06-01
影响因子：
3.4
通讯作者：
Mekhail, T.
中科院分区：
文献类型：
--
作者：
Kalmadi, S.;Davis, M.;Mekhail, T.
前言：来那度胺是沙利度胺的一种免疫调节衍生物，具有显著更强的体外活性和不同的毒性。在临床前试验中，它已经显示出与化疗的协同作用。患者和方法：这项研究的主要目标是在标准的I期试验设计中确定多西他赛和卡铂联合口服来那度胺时的最大耐受量。2004年9月至2005年5月，14名经病理证实的实体瘤患者，=3级非血液学毒性或4级血液学毒性。结果：4例患者中有3例出现DLT(2例为3级电解质改变，1例为4级中性粒细胞减少症)，剂量为1级，多西紫杉醇60 mg/m(2)+卡铂AUC 6，第1天口服来那度胺10 mg/d，共21天。10例患者第1天口服多西紫杉醇60 mg/m(2)+卡铂AUC6，第1天口服来那度胺5 mg，第1~14天口服来那度胺1个DLT(4级中性粒细胞减少)。没有与治疗相关的死亡或不可逆转的毒性。在14例可评价疗效的患者中，5例(9例非小细胞肺癌患者中5例)部分缓解。结论：多西紫杉醇60 mg/m(2)+卡铂AUC6 d1，来那度胺5 mg，每日1次口服，21 d周期的第1~14天是不使用预防性生长因子的最大耐受量。这种联合是有效的，有必要在第二阶段试验中进行进一步评估。
Introduction: Lenalidomide is an immunomodulatory derivative of thalidomide with significantly greater in vitro activity and a different toxicity profile. In preclinical trials it has shown synergy with chemotherapy.Patients and methods: Primary objective of this study was to determine the maximum tolerated doses of docetaxel and carboplatin when combined with oral lenalidomide in a standard phase I study design. Between September 2004 and May 2005, 14 patients with pathologically proven solid tumors, = grade 3 non-hematological, or grade 4 hematological toxicity. No growth factors were used during cycle 1.Results: Three of four patients treated at dose level 1, docetaxel 60 mg/m(2) and carboplatin AUC 6 on Day 1, and lenalidomide 10 mg orally daily on Days 1-14 of a 21 day cycle experienced DLT (grade 3 electrolyte changes in two patients, and grade 4 neutropenia in one patient). Ten patients were treated at dose level -1, docetaxel 60 mg/m(2) and carboplatin AUC 6 on Day 1, and lenalidomide 5 mg orally daily on Days 1-14 of a 21 day cycle with one DLT (Grade 4 neutropenia). There were no treatment-related deaths or irreversible toxicities. Of the 14 response-evaluable patients, five achieved a partial response (5 out of 9 patients with non-small cell lung cancer.Conclusions: Docetaxel 60 mg/m(2) and carboplatin AUC 6 on Day 1, with lenalidomide 5 mg orally daily on Days 1-14 days of a 21 day cycle is the maximum tolerated dose without the use of prophylactic growth factors. This combination is active and further evaluation in a phase II trial is warranted.