Irinotecan therapy in adults with recurrent or progressive malignant glioma
Irinotecan therapy in adults with recurrent or progressive malignant glioma
复制标题
DOI：
10.1200/jco.1999.17.5.1516
复制
发表时间：
1999-05-01
影响因子：
45.3
通讯作者：
Miller, LL
中科院分区：
文献类型：
--
作者：
Friedman, HS;Petros, WP;Miller, LL
目的：确定伊立替康（CPT-11, Camptosar; Pharmacia & Upjohn, Kalamazoo， MI）治疗进行性、持续性或复发性成人恶性胶质瘤的活性、毒性和药代动力学。患者和方法：在1996年10月至1997年8月期间，进行性或复发性恶性胶质瘤患者被纳入本研究。CPT-11以125 mg/m(2)的剂量进行90分钟静脉（IV）输注，每周一次，持续4周，然后休息2周，其中包括一个疗程。在一组患者中测定CPT-11及其代谢物SN-38和SN-38葡萄糖醛酸盐（SN-38G）的血浆浓度。结果：所有入组的60名患者（36名男性和24名女性）均接受了CPT-11治疗，所有患者的毒性、反应和生存率均可评估。32例患者的药代动力学数据可用。9名患者（15%；95%可信区间，6%至24%）证实部分缓解，33名患者（55%）病情稳定，持续时间超过两个疗程（12周）。在研究中观察到的毒性仅限于罕见的中性粒细胞减少、恶心、呕吐和腹泻。这些患者的CPT-11、SN-38和SN-38G在无限时间值下的血浆浓度-时间曲线下的面积分别约为先前未接受抗癫痫药物或慢性地塞米松治疗的转移性结直肠癌患者的40%、25%和25%。结论：反应结果表明，以标准起始剂量和治疗方案给予CPT-11，对复发性恶性胶质瘤患者具有活性。然而，在该患者群体中，严重毒性发生率低，CPT-11和SN-38的血浆浓度低，表明抗惊厥药和地塞米松同时治疗可增强药物清除率。[J]中华临床杂志，17(5):1516-1525。(C) 1999年由美国临床肿瘤学会出版。
Purpose: To determine the activity, toxicity, and pharmacokinetics of irinotecan (CPT-11, Camptosar; Pharmacia & Upjohn, Kalamazoo, MI) in the treatment of adults with progressive, persistent, or recurrent malignant glioma.Patients and Methods: Patients with progressive or recurrent malignant gliomas were enrolled onto this study between October 1996 and August 1997. CPT-11 was given as a 90-minute intravenous (IV) infusion at a dose of 125 mg/m(2) once weekly for 4 weeks followed by a 2-week rest, which comprised one course. Plasma concentrations of CPT-11 and its metabolites, SN-38 and SN-38 glucuronide (SN-38G), were determined in a subset of patients.Results: All 60 patients who enrolled (36 males and 24 females) were treated with CPT-11 and all were assessable for toxicity, response, and survival. Pharmacokinetic data were available in 32 patients. Nine patients (15%; 95% confidence interval, 6% to 24%) had a confirmed partial response, and 33 patients (55%) achieved stable disease lasting more than two courses (12 weeks). Toxicity observed during the study was limited to infrequent neutropenia, nausea, vomiting, and diarrhea. CPT-11, SN-38, and SN-38G area under the plasma concentration-time curves through infinite time valuer in these patients were approximately 40%, 25%, and 25%, respectively, of those determined previously in patients with metastatic colorectal cancer not receiving antiepileptics or chronic dexamethasone treatment.Conclusion: Response results document that CPT-11, given with a standard starting dose and treatment schedule, has activity in patients with recurrent malignant glioma. However, the low incidence of severe toxicity and low plasma concentrations of CPT-11 and SN-38 achieved in this patient population suggest that concurrent treatment with anticonvulsants and dexamethasone enhances drug clearance. J Clin Oncol 17:1516-1525. (C) 1999 by American Society of Clinical Oncology.