Morantz R A, Kimler B F, Vats T S, Henderson S D
J Neurooncol. 1983;1(3):249-55. doi: 10.1007/BF00165609.
A logical inference from the recent reports indicating that malignant brain tumors are composed of a heterogeneous cell population is that combination chemotherapy will be required for effective brain tumor control. For several years we have been investigating the use of Bleomycin as an agent to be used in conjunction with radiation therapy and a nitrosourea compound. Since systemically administered Bleomycin does not cross the blood-brain-barrier and has significant toxicity when used parenterally in high doses, we have studied the use of smaller doses of Bleomycin injected directly into the brain tumor cavity. Such an intracerebral dose was more effective in prolonging survival of rats burdened with experimental 9L gliosarcomas than an intravenous dose that is 25 times as great. The combination of intracerebrally administered Bleomycin and radiation therapy was more effective than either modality alone. Furthermore, the combination of Bleomycin delivered intracerebrally and BCNU given systemically was more effective than either agent used alone. Finally, in a Phase I clinical of Bleomycin given via an Ommaya reservoir to eight patients with recurrent malignant brain tumors, we have demonstrated that individual doses of up to 7.5 units and cumulative doses of up to 255 units can be administered without significant toxicity.
近期报告表明恶性脑肿瘤由异质性细胞群体组成，由此合理推断，要有效控制脑肿瘤需要联合化疗。数年来，我们一直在研究将博来霉素用作与放射治疗及亚硝基脲化合物联合使用的药物。由于全身给药的博来霉素无法穿过血脑屏障，且大剂量肠胃外给药时有显著毒性，我们研究了将小剂量博来霉素直接注入脑肿瘤腔的用法。这样的脑内给药剂量在延长荷实验性9L胶质肉瘤大鼠的生存期方面比25倍剂量的静脉给药更有效。脑内给药的博来霉素与放射治疗联合使用比单独使用任何一种方式都更有效。此外，脑内给药的博来霉素与全身给药的卡氮芥联合使用比单独使用任何一种药物都更有效。最后，在一项通过奥马亚贮液器给8例复发性恶性脑肿瘤患者使用博来霉素的I期临床试验中，我们已证明，单次剂量高达7.5单位、累积剂量高达255单位给药时均无明显毒性。
