Ewend M G, Williams J A, Tabassi K, Tyler B M, Babel K M, Anderson R C, Pinn M L, Brat D J, Brem H
Department of Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Cancer Res. 1996 Nov 15;56(22):5217-23.
Local chemotherapy with biodegradable polymers prolongs survival with minimal morbidity in patients with intracranial high-grade gliomas. However, use of local chemotherapy for metastatic brain tumors has not been defined. We studied the safety and the efficacy of locally delivered chemotherapy with and without concurrent radiation therapy in treating tumors that frequently metastasize to the brain. The chemotherapeutic agents 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), carboplatin, and camptothecin were incorporated into controlled-release polymers and tested individually against intracranial challenges with one of four tumors (lung carcinoma, renal cell carcinoma, colon carcinoma, and melanoma). For each combination of drug and tumor type, four groups were tested: (a) empty polymer (no drug); (b) external beam radiotherapy (XRT) alone; (c) local chemotherapy from biodegradable polymer alone; and (d) local chemotherapy and XRT together. Polymers were implanted 5 days after tumor inoculation; XRT was given on days 7-9 (300 cGy/day). BCNU and XRT together were effective against all four tumors. BCNU polymer alone significantly prolonged survival in mice with intracranial melanoma or renal cell carcinoma. Carboplatin alone was effective against both melanoma and colon carcinoma and in combination with XRT against colon and renal cell carcinomas. Camptothecin was effective only with XRT against melanoma. These studies demonstrate that local delivery of chemotherapy with concurrent radiation therapy is safe and can significantly prolong survival in models of common intracranial metastatic tumors. Concurrent use of local chemotherapy with standard XRT appears to be more effective than either treatment alone. Local chemotherapy may also be of benefit to patients who have previously received maximal cranial irradiation but suffer an intracranial recurrence.
使用可生物降解聚合物进行局部化疗可延长颅内高级别胶质瘤患者的生存期，且发病率最低。然而，局部化疗在转移性脑肿瘤中的应用尚未明确。我们研究了在有或无同步放疗的情况下，局部给药化疗治疗常见脑转移瘤的安全性和疗效。将化疗药物1,3-双(2-氯乙基)-1-亚硝基脲(BCNU)、卡铂和喜树碱掺入控释聚合物中，并分别针对四种肿瘤(肺癌、肾细胞癌、结肠癌和黑色素瘤)之一的颅内挑战进行测试。对于每种药物和肿瘤类型的组合，测试四组：(a)空聚合物(无药物)；(b)单纯外照射放疗(XRT)；(c)仅来自可生物降解聚合物的局部化疗；(d)局部化疗和XRT联合使用。在肿瘤接种后5天植入聚合物；在第7 - 9天给予XRT(300 cGy/天)。BCNU和XRT联合对所有四种肿瘤均有效。单独使用BCNU聚合物可显著延长颅内黑色素瘤或肾细胞癌小鼠的生存期。单独使用卡铂对黑色素瘤和结肠癌均有效，与XRT联合对结肠癌和肾细胞癌有效。喜树碱仅与XRT联合对黑色素瘤有效。这些研究表明，同步放疗下局部给药化疗是安全的，并且可以显著延长常见颅内转移瘤模型的生存期。局部化疗与标准XRT联合使用似乎比单独任何一种治疗都更有效。局部化疗对先前接受过最大剂量颅脑照射但发生颅内复发的患者可能也有益处。
