Schedule-dependent activity of irinotecan plus BCNU against malignant glioma xenografts
Schedule-dependent activity of irinotecan plus BCNU against malignant glioma xenografts
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DOI：
10.1007/s002800050050
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发表时间：
2000-04-01
影响因子：
3
通讯作者：
Bigner, DD
中科院分区：
文献类型：
--
作者：
Friedman, HS;Castellino, RC;Bigner, DD
目的：进一步评价伊立替康（CPT-11）联合1，3-双-（氯乙基）-1-亚硝基脲（BCNU）治疗无胸腺裸鼠中枢神经系统肿瘤源性异种移植瘤的活性。方法：我们报告的研究评估该方案在治疗恶性胶质瘤异种移植D-54 MG的时间表依赖性。结果如下：BCNU和CPT-11联合使用时，BCNU在第1天给药，CPT-11在第1-5天和第8-12天给药时显示出最高的增强指数（2.0-3.3）。CPT-11给药延迟至第3天或第5天显著降低活性，增强指数分别为1.6-1.8和0.6-1.0。延迟BCNU给药至第8天也降低了CPT-11活性，增强指数为1.2-1.4。结论：这些结果表明，在CPT-11给药前存在BCNU诱导的加合物或可能的交联对于增强活性至关重要。虽然这种增强的机制目前尚不清楚，但基于这些结果，CPT-11加BCNU治疗复发性恶性胶质瘤成人的I期试验正在进行中。
Purpose: To further evaluate the activity of irinotecan (CPT-11) plus 1,3-bis-(chloroethyl)-1-nitrosourea (BCNU) in the treatment of central nervous system tumor-derived xenografts in athymic nude mice. Methods: We report studies evaluating the schedule-dependence of this regimen in the treatment of the malignant glioma xenograft D-54 MG. Results: The combination of BCNU and CPT-11 showed the highest enhancement index (2.0-3.3) when BCNU was given on day 1 and CPT-11 was given on days 1-5 and 8-12. Delay of CPT-11 administration to day 3 or day 5 substantially decreased activity with enhancement indices of 1.6-1.8 and 0.6-1.0, respectively. Delay of BCNU administration to day 8 also reduced the CPT-11 activity with enhancement indices of 1.2-1.4. Conclusions: These results suggest that the presence of a BCNU-induced adduct or possibly crosslink prior to administration of CPT-11 is critical for enhanced activity. Although the mechanism of this enhancement is not currently known, a phase I trial of CPT-11 plus BCNU for adults with recurrent malignant glioma based on these results is in progress.