Interstitial chemotherapy of experimental brain tumors: Comparison of intratumoral injection versus polymeric controlled release
Interstitial chemotherapy of experimental brain tumors: Comparison of intratumoral injection versus polymeric controlled release
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DOI：
10.1007/bf01060216
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发表时间：
1995-11-01
影响因子：
3.9
通讯作者：
Brem, H
中科院分区：
文献类型：
--
作者：
Buahin, KG;Brem, H
控释聚合物间质化疗是治疗恶性胶质瘤的一种临床辅助手段。需要聚合物来释放化疗药物，而不是简单地将药物注射到肿瘤中，这需要进一步的研究。因此，我们比较了直接病灶内注射卡莫司汀（BCNU）和4-氢过氧环磷酰胺（4 HC）到大鼠脑肿瘤床与通过颅内植入控释聚合物递送的相同药物的效果。在将9 L胶质肉瘤颅内植入雄性大鼠后第5天开始治疗;瘤内注射两个剂量的每种药物，代表在前24小时内通常从聚合物体内释放的药物量，或每种聚合物上负载的最大药物。对照大鼠用空聚合物处理。我们发现，在肿瘤内注射BCNU的大鼠组中，中位寿命延长（1 mg和2 mg剂量分别为23%和36%），而BCNU浸渍聚合物组为271%。瘤内4 HC的结果相似（0.1 mg和2 mg注射剂量分别为21%和36%），4 HC浸渍聚合物的结果为121%。然而，肿瘤内注射后的总生存率与对照组大鼠相比没有统计学显著差异（p > 0.05）。此外，存活率的改善并不一致，一些接受4 HC注射的动物在治疗过程中早期死亡。与对照组大鼠相比，聚合物治疗导致统计学显著的存活延长（BCNU和4 HC均p < 0.001）。我们的结论是，在大鼠模型中，直接病灶内注射BCNU和4 HC比通过聚合物控制释放治疗9 L胶质肉瘤的效果差。
Interstitial chemotherapy with controlled release polymers is a clinical adjunct in the management of malignant gliomas. The need for polymer to release the chemotherapeutic drug rather than simply injecting the drug into the tumor warrants further investigation. Therefore, we compared the effects of direct intralesional injection of carmustine (BCNU) and 4-hydroperoxycyclophosphamide (4HC) into the rat brain tumor bed with those from the same agents delivered via controlled release polymers implanted intracranially. Treatment was initiated on the fifth day after intracranial implantation of 9L gliosarcoma into male rats; two doses of each drug were injected intratumorally, representing either the amount of drug typically released in vivo from polymer during the first 24 h, or the maximal drug loaded on each polymer. Control rats were treated with empty polymers. We found that the median lifespan was extended in the groups of rats treated with intratumoral injection of BCNU (23% and 36% for 1 mg and 2 mg doses), and 271% with BCNU-impregnated polymer. Similar results were found with intratumoral 4HC (21% and 36% for 0.1 mg and 2 mg injection doses), and 121% with 4HC-impregnated polymer. Overall survival after intraneoplastic injections, however, was not statistically significantly different from that of control rats (p > 0.05). Furthermore, improvement in survival was not consistent, and some animals subjected to 4HC injection died early in the course of treatment. Polymeric treatment resulted in statistically significant prolongation of survival, compared to control rats (p < 0.001 for both BCNU and 4HC). We conclude that direct intralesional injection of BCNU and 4HC is less effective than controlled release via polymers for the treatment of 9L gliosarcoma in the rat model.