A phase 2 trial of irinotecan (CPT-11) in patients with recurrent malignant glioma: A North American Brain Tumor Consortium study
A phase 2 trial of irinotecan (CPT-11) in patients with recurrent malignant glioma: A North American Brain Tumor Consortium study
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DOI：
10.1215/15228517-2005-010
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发表时间：
2006-04-01
期刊：
影响因子：
15.9
通讯作者：
Kuhn, J
中科院分区：
文献类型：
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作者：
Prados, MD;Lamborn, K;Kuhn, J
本研究的目的是确定CPT-11每三周给药一次对患有进行性恶性胶质瘤的成年人的反应，这些患者接受或不接受酶诱导抗癫痫药物（EIAED）治疗，推荐的2期剂量来自先前的1期研究。年龄≥ 18岁、KPS ≥ 60、患有可测量的复发性III级间变性胶质瘤（AG）或IV级多形性胶质母细胞瘤（GBM）的成人患者符合条件。既往化疗不允许超过一次，无论是作为辅助治疗还是复发性疾病。CPT-11的剂量为350 mg/m2，每3周一次，在未接受EIAED治疗的患者中为静脉注射，在接受EIAED治疗的患者中为750 mg/m2。病情稳定或缓解的患者可以接受治疗，直至肿瘤进展或治疗总计12个月。该研究的主要终点是确定CPT-11。可显著延缓肿瘤进展，采用6个月无进展生存率（PFS-6）。该试验的规模能够区分单独GBM组的15%和35%的比率以及整个队列的20%和40%的比率。入组了51例合格患者，包括38例GBM和13例AG患者。中位年龄分别为52岁和42岁。整个队列的PFS-6为1.7.6%。GBM患者的PFS-6为15.7%（95%置信区间[CI]，0.07-0.31），AG患者为23%（95% CI，0.07-0.52）。该组的毒性包括腹泻和骨髓抑制。我们得出结论，CPT-11的推荐2期剂量的患者或没有EIAED是无效的，在这个时间表，在这个病人群体。
The purpose of this study was to determine the response to CPT-11 administered every three weeks to adults with progressive malignant glioma, treated with or without enzyme-inducing antiepileptic drug (EIAED) therapy, at the recommended phase 2 dose determined from a previous phase 1 study. Adult patients age 18 or older with a KPS of 60 or higher who had measurable recurrent grade III anaplastic glioma (AG) or grade IV glioblastoma multiforme (GBM) were eligible. No more than one prior chemotherapy was allowed, either as adjuvant therapy or for recurrent disease. The CPT-11 dose was 350 mg/m(2) i.v. every three weeks in patients not on EIAED and 750 mg/m(2) in patients on EIAED therapy. Patients with stable or responding disease could be treated until tumor progression or a total of 12 months of therapy. The primary end point of the study was to determine whether CPT-11. could significantly delay tumor progress on, using the rate of six-month progression-free survival (PFS-6). The trial was sized to be able to discriminate between a 15% and 35% rate for the GBM group alone and between a 20% and 40% rate for the entire cohort. There were 51 eligible patients, including 38 GBM and 13 AG patients, enrolled. The median age was 52 and 42 years, respectively. PFS-6 for the entire cohort was 1.7.6%. PFS-6 was 15.7% (95% confidence interval [CI], 0.07-0.31) for the GBM patients and 23% (95% CI, 0.07-0.52) for AG patients. Toxicity for the group included diarrhea and myelosuppression. We conclude that the recommended phase 2 dose of CPT-11 for patients with or without EIAED was ineffective on this schedule, in this patient population.