一项关于紫杉醇治疗复发性恶性胶质瘤患者的II期研究，根据抗惊厥药物的联合使用情况采用不同剂量：北美脑肿瘤联盟报告。

A Phase II study of paclitaxel in patients with recurrent malignant glioma using different doses depending upon the concomitant use of anticonvulsants: a North American Brain Tumor Consortium report.

作者信息

Chang S M, Kuhn J G, Robins H I, Schold S C, Spence A M, Berger M S, Mehta M, Pollack I F, Rankin C, Prados M D

机构信息

Department of Neurosurgery, University of California Medical Center, San Francisco, California, USA.

出版信息

Cancer. 2001 Jan 15;91(2):417-22. doi: 10.1002/1097-0142(20010115)91:2<417::aid-cncr1016>3.0.co;2-9.

DOI:10.1002/1097-0142(20010115)91:2<417::aid-cncr1016>3.0.co;2-9

PMID:11180089

Abstract

BACKGROUND

The primary objective of the current study was to determine the response rate of paclitaxel in patients with recurrent malignant glioma by using different doses dependent on the concomitant use of anticonvulsants. Secondary objectives were to determine the time period to treatment failure, to evaluate toxicities, and to obtain pharmacokinetic data.

METHODS

Adult patients who had recurrent malignant glioma were treated with paclitaxel. Patients were treated at different doses depending on the concomitant use of anticonvulsants known to induce the p450 hepatic enzyme system. Patients on such agents were treated at a dose of 330 mg/m2, whereas those not on these anticonvulsants were treated at a dose of 210 mg/m2. Tumor response was assessed at 6-week intervals. Treatment was continued until documented tumor progression or unacceptable toxicity occurred, or a total of 12 paclitaxel infusions was completed.

RESULTS

From January 1997 to June 1997, 23 patients were treated with paclitaxel. Four patients were ineligible for the current study. Of the 19 eligible patients, there were no responses seen. Four (21%) had stabilization of disease. Median time to treatment failure was 1 month (95% confidence interval [CI], 1-2 mos) and median survival was 7 months (95% CI, 6-10 mos). Three patients were removed from the current study because they had toxicity. Pharmacokinetic studies demonstrated that drug levels and clearance values were consistent with previously reported findings.

CONCLUSION

Even though higher doses were administered to patients who had recurrent malignant glioma and who were on concomitant anticonvulsants, there were no objective responses to paclitaxel. Time to tumor progression was 1 month. Further testing of paclitaxel at this dose schedule does not appear to be warranted in this patient population.

摘要

背景

本研究的主要目的是通过根据抗惊厥药物的联合使用情况采用不同剂量来确定紫杉醇对复发性恶性胶质瘤患者的缓解率。次要目的是确定治疗失败的时间、评估毒性以及获取药代动力学数据。

方法

患有复发性恶性胶质瘤的成年患者接受紫杉醇治疗。根据已知会诱导肝脏p450酶系统的抗惊厥药物的联合使用情况，患者接受不同剂量的治疗。使用此类药物的患者接受330mg/m²的剂量治疗，而未使用这些抗惊厥药物的患者接受210mg/m²的剂量治疗。每隔6周评估一次肿瘤反应。治疗持续进行，直到记录到肿瘤进展或出现不可接受的毒性，或者总共完成12次紫杉醇输注。

结果

从1997年1月至1997年6月，23例患者接受了紫杉醇治疗。4例患者不符合本研究的条件。在19例符合条件的患者中，未见缓解情况。4例（21%）疾病稳定。治疗失败的中位时间为1个月（95%置信区间[CI]，1 - 2个月），中位生存期为7个月（95%CI，6 - 10个月）。3例患者因毒性反应退出本研究。药代动力学研究表明，药物水平和清除值与先前报道的结果一致。