Castellino R C, Elion G B, Keir S T, Houghton P J, Johnson S P, Bigner D D, Friedman H S
Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Cancer Chemother Pharmacol. 2000;45(4):345-9. doi: 10.1007/s002800050050.
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.
We report studies evaluating the schedule-dependence of this regimen in the treatment of the malignant glioma xenograft D-54 MG.
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.
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.
进一步评估伊立替康（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异种移植瘤的活性。
我们报告了评估该方案治疗恶性胶质瘤异种移植瘤D - 54 MG时疗程依赖性的研究。
当BCNU在第1天给药，CPT - 11在第1 - 5天和第8 - 12天给药时，BCNU与CPT - 11联合显示出最高的增强指数（2.0 - 3.3）。将CPT - 11给药延迟至第3天或第5天会显著降低活性，增强指数分别为1.6 - 1.8和0.6 - 1.0。将BCNU给药延迟至第8天也会降低CPT - 11的活性，增强指数为1.2 - 1.4。
这些结果表明，在给予CPT - 11之前存在BCNU诱导的加合物或可能的交联对于增强活性至关重要。尽管目前尚不清楚这种增强的机制，但基于这些结果，一项针对复发性恶性胶质瘤成人患者的CPT - 11联合BCNU的I期试验正在进行中。
