Intermittent Erlotinib in Combination with Pemetrexed Phase I Schedules Designed to Achieve Pharmacodynamic Separation
Intermittent Erlotinib in Combination with Pemetrexed Phase I Schedules Designed to Achieve Pharmacodynamic Separation
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DOI：
10.1097/jto.0b013e3181a94b08
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发表时间：
2009-07-01
影响因子：
20.4
通讯作者：
Gandara, David R.
中科院分区：
文献类型：
--
作者：
Davies, Angela M.;Ho, Cheryl;Gandara, David R.
简介：表皮生长因子受体酪氨酸激酶抑制剂与化疗同时使用与单用化疗相比不能改善晚期非小细胞肺癌（NSCLC）患者的预后。通过间歇性递送表皮生长因子受体酪氨酸激酶抑制剂与化疗的药效学分离可能通过克服假设的antagonistics.Methods：两个剂量递增的I期试验（A组和13组）同时进行。培美曲塞每21天给药一次（500 mg/m2静脉注射）。在A组中，在第2、9和16天每周给予厄洛替尼（800-1400 mg）。在第13组中，在第2 - 16天给予厄洛替尼（150-250 mg）。结果：42例晚期实体瘤患者，包括16例NSCLC，接受了治疗。患者特征包括中位年龄63岁（范围，29-77岁），19名男性，Karnofsky体力状态>= 90/
Introduction: Epidermal growth factor receptor tyrosine kinase inhibitors given concurrently with chemotherapy do not improve patient outcomes compared with chemotherapy alone in advanced non-small cell lung cancer (NSCLC). Pharmacodynamic separation by intermittent delivery of epidermal growth factor receptor tyrosine kinase inhibitors with chemotherapy may increase efficacy by overcoming hypothesized antagonism.Methods: Two dose-escalating phase I trials (arm A and arm 13) were conducted simultaneously. Pemetrexed was given every 21 days (500 mg/m(2) intravenously). In arm A, erlotinib was given weekly on days 2, 9, and 16 (800-1400 mg). In arm 13, erlotinib was given on days 2 to 16 (150-250 mg). Patients continued therapy until disease progression or unacceptable toxicity.Results: Forty-two patients with advanced solid tumors, including 16 NSCLC, were treated. Patient characteristics included median age of 63 (range, 29-77), 19 males, and Karnofsky performance status >= 90/