Friedman H S, Houghton P J, Schold S C, Keir S, Bigner D D
Department of Pediatrics, Duke University Medical Center, Durham, NC 27710.
Cancer Chemother Pharmacol. 1994;34(2):171-4. doi: 10.1007/BF00685936.
The activity of dimethylaminomethyl-10-hydroxycamptothecin (topotecan) was evaluated against a panel of xenografts derived from ependymomas (D528 EP, D612 EP), childhood high-grade gliomas (D-456 MG, D-212 MG), adult high-grade gliomas (D-245 MG, D-54 MG), and medulloblastomas (D425 Med) growing s.c. and i.c. (intracranially) in athymic nude mice. Topotecan was given at a dose of 1.9 mg/kg by i.p. injection in 0.9% saline using a volume of 90 ml/m2 on days 1-5 and 8-12, which represents the dose lethal to 10% of treated animals. Topotecan was active in the therapy of all s.c. xenografts tested, with growth delays ranging from 6.3 days in D-54 MG to 55.7 days in D528 EP. Topotecan produced statistically significant tumor regressions in D425 Med, D-456 MG, D-245 MG, D528 EP, and D612 EP. No tumor regression was seen in any control animal. Statistically significant increases in median survival were seen in the two i.c. xenografts--D-456 MG (28.6% increase) and D-54 MG (39% increase)--treated with topotecan. These studies suggest that topotecan may be an important new addition to the therapy of central nervous system tumors.
对二甲基氨基甲基-10-羟基喜树碱（拓扑替康）的活性进行了评估，该评估针对的是一组源自室管膜瘤（D528 EP、D612 EP）、儿童高级别胶质瘤（D - 456 MG、D - 212 MG）、成人高级别胶质瘤（D - 245 MG、D - 54 MG）以及髓母细胞瘤（D425 Med）的异种移植瘤，这些异种移植瘤在无胸腺裸鼠体内皮下和颅内生长。拓扑替康以1.9 mg/kg的剂量通过腹腔注射给予，使用0.9%生理盐水，体积为90 ml/m²，在第1 - 5天和第8 - 12天给药，该剂量对10%的受试动物具有致死性。拓扑替康对所有测试的皮下异种移植瘤治疗均有活性，生长延迟范围从D - 54 MG中的6.3天到D528 EP中的55.7天。拓扑替康在D425 Med、D - 456 MG、D - 245 MG、D528 EP和D612 EP中产生了具有统计学意义的肿瘤消退。在任何对照动物中均未观察到肿瘤消退。在用拓扑替康治疗的两个颅内异种移植瘤——D - 456 MG（增加28.6%）和D - 54 MG（增加39%）中，观察到中位生存期有统计学意义的增加。这些研究表明，拓扑替康可能是中枢神经系统肿瘤治疗中的一项重要新补充。
