Preirradiation paclitaxel in glioblastoma multiforme: Efficacy, pharmacology, and drug interactions
Preirradiation paclitaxel in glioblastoma multiforme: Efficacy, pharmacology, and drug interactions
复制标题
DOI：
10.1200/jco.1997.15.9.3121
复制
发表时间：
1997-09-01
影响因子：
45.3
通讯作者：
Piantadosi, S
中科院分区：
文献类型：
--
作者：
Fetell, MR;Grossman, SA;Piantadosi, S
目的：本研究的目的是确定新诊断的多形性胶质母细胞瘤患者以最大耐受剂量（MTD）给予紫杉醇的反应率。患者和方法：在这项多中心研究中，所有患者年龄均在45岁或以上，术后MRI扫描显示有可测量的残余肿瘤。放射前连续96小时静脉输注紫杉醇3个周期，前提是肿瘤在连续mri上没有扩大。最初的10名患者接受了先前推荐的140 mg/m的II期剂量治疗(2)。由于毒性低于预期，在24例患者中开展了一项I/II期研究，在接受（+EIAED）或未接受（-EIAED）联合酶诱导抗癫痫药物的患者中，紫杉醇剂量分别递增。在化疗的第一个周期测量紫杉醇血浆稳态浓度（Css）。缓解是本研究的主要疗效终点，但也评估了生存期。结果：-EIAED组MTD为140 mg/m(2)， +EIAED组MTD为200 mg/m(2)。140 mg/m(2)治疗-EIAED患者的平均Css为38 nM，而+EIAED患者的平均Css为140 mg/m(2)时17 nM， 175 mg/m(2)时27 nM， 200 mg/m(2)时46 nM， 230 mg/m(2)时51 nM。一个病人，谁有一个验证的部分反应，但他的诊断改变为间变性少突胶质细胞瘤在随后的中枢神经病理检查。接受MTD或以上剂量治疗的15例可评估的胶质母细胞瘤患者均未显示紫杉醇放射学反应。该方案中符合条件的患者的中位生存期为355天（95% CI， 255至485天），与采用常规治疗的同类患者的生存期相似。结论：这些结果表明：(1)在MTD处输注96小时紫杉醇对未治疗的胶质母细胞瘤患者的活性最小；(2)同时给予EIAEDs改变了紫杉醇的药理学，导致更低的Css，降低了全身毒性和更高的剂量要求；(3)本研究设计，在放射治疗之前给予一种新的药物（与MRI连续监测），没有对该患者群体的生存产生不利影响。(C) 1991年美国临床肿瘤学会。
Purpose: The purpose of this study was to determine the response rate of paclitaxel administered at maximal tolerated doses (MTD) in patients with newly diagnosed glioblastoma multiform.Patients and Methods: All patients in this multicenter study were 45 years or older and had measurable residual tumor on postoperative MRI scans. Up to 3 cycles of paclitaxel were administered as a continuous 96-hour intravenous infusion prior to radiation, provided that the tumor did not enlarge on serial MRIs. The initial 10 patients were treated with the previously recommended phase II dose of 140 mg/m(2). Less than anticipated toxicity led to the development of a phase I/II study in 24 patients in which paclitaxel doses were escalated separately in patients receiving (+EIAED) or not receiving (-EIAED), concomitant enzyme-inducing antiepileptic drugs. Paclitaxel plasma steady state concentrations (Css) were measured during the first cycle of chemotherapy. Response was the primary efficacy endpoint for this study, although survival was also assessed.Results: The MTD was 140 mg/m(2) in the -EIAED, and 200 mg/m(2) in the +EIAED patient groups. The mean Css for the -EIAED patients treated at 140 mg/m(2) was 38 nM, whereas the mean Css for +EIAED patients were 17 nm at 140 mg/m(2), 27 nM at 175 mg/m(2), 46 nM at 200 mg/m(2), and 51 nM at 230 mg/m(2). One patient, who had a verified partial response, herd his diagnosis changed to an anaplastic oligodendroglioma on subsequent central neuropathologic review. None of the 15 assessable glioblastoma patients treated at or above the MTD doses showed a radiographic response to paclitaxel. The median survival of eligible patients on this protocol was 355 days (95% CI, 255 to 485 days), which is similar to the survival of comparable patients treated with conventional therapy.Conclusions: These results suggest that (1) paclitaxel given as a 96-hour infusion at the MTD has minimal activity in patients with untreated glioblastoma, (2) the concomitant administration of EIAEDs alters the pharmacology of paclitaxel, resulting in a lower Css, reduced systemic toxicity, and higher dose requirements, (3) this study design, in which a new agent is given prior to radiation therapy (with serial monitoring of MRI), did not adversely affect survival in this patient population. (C) 1991 by American Society of Clinical Oncology.