卡铂 convection-enhanced delivery 联合放疗治疗脑肿瘤。
Convection enhanced delivery of carboplatin in combination with radiotherapy for the treatment of brain tumors.
机构信息
Department of Pathology, The Ohio State University, 165 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210, USA.
出版信息
J Neurooncol. 2011 Feb;101(3):379-90. doi: 10.1007/s11060-010-0272-z. Epub 2010 Jun 25.
The purpose of this study was to further evaluate the therapeutic efficacy of convection enhanced delivery (CED) of carboplatin in combination with radiotherapy for treatment of the F98 rat glioma. Tumor cells were implanted stereotactically into the brains of syngeneic Fischer rats, and 13 or 17 d. later carboplatin (20 μg/10 μl) was administered by either CED over 30 min or by Alzet osmotic pumps (0.5 μg/μl/h for 168 h.) beginning at 7 d after tumor implantation. Rats were irradiated with a 15 Gy fractionated dose (5 Gy × 3) of 6 MV photons to the whole brain beginning on the day after drug administration. Other groups of rats received either carboplatin or X-irradiation alone. The tumor carboplatin concentration following CED of 20 μg in 10 μl was 10.4 μg/g, which was equal to that observed following i.v. administration of 100 mg/kg b.w. Rats bearing small tumors, treated with carboplatin and X-irradiation, had a mean survival time (MST) of 83.4 d following CED and 111.8 d following pump delivery with 40% of the latter surviving >180 d (i.e. cured) compared to 55.2 d for CED and 77.2 d. for pump delivery of carboplatin alone and 31.8 d and 24.2 d, respectively, for X-irradiated and untreated controls. There was no microscopic evidence of residual tumor in the brains of all long-term survivors. Not surprisingly, rats with large tumors had much shorter MSTs. Only modest increases in MSTs were observed in animals that received either oral administration or CED of temozolomide plus X-irradiation (23.2 d and 29.3 d) compared to X-irradiation alone. The present survival data, and those previously reported by us, are among the best ever obtained with the F98 glioma model. Initially, they could provide a platform for a Phase I clinical trial to evaluate the safety and potential therapeutic efficacy of CED of carboplatin in patients with recurrent glioblastomas, and ultimately a Phase II trial of carboplatin in combination with radiation therapy.
本研究的目的是进一步评估卡铂对流增强递送（CED）联合放疗治疗 F98 大鼠脑胶质瘤的疗效。将肿瘤细胞立体定向植入同基因 Fischer 大鼠脑内，在 13 或 17d 后，于肿瘤植入后 7d 开始，通过 CED 输注 30min（20μg/10μl）或 Alzet 渗透泵（0.5μg/μl/h，共 168h）给予卡铂。在药物给药后第二天，对大鼠进行 15Gy 分割剂量（5Gy×3）的 6MV 光子全脑照射。其他大鼠单独接受卡铂或 X 射线照射。CED 给予 20μg 的 10μl 肿瘤卡铂浓度为 10.4μg/g，与静脉给予 100mg/kg 体重的卡铂浓度相等。接受卡铂和 X 射线治疗的小型肿瘤大鼠的中位生存时间（MST）为 CED 后 83.4d，泵输送后 111.8d，后者有 40%的大鼠存活时间>180d（即治愈），而 CED 为 55.2d，泵输送卡铂单独为 77.2d，X 射线照射和未处理的对照组分别为 31.8d 和 24.2d。所有长期存活者的大脑中均无残留肿瘤的显微镜证据。毫不奇怪，患有大肿瘤的大鼠 MST 短得多。与单独 X 射线照射相比，接受口服或 CED 替莫唑胺联合 X 射线照射的动物 MST 仅略有增加（23.2d 和 29.3d）。目前的生存数据以及我们之前报告的数据，是 F98 神经胶质瘤模型中获得的最好数据之一。最初，它们可以为一项 I 期临床试验提供平台，以评估复发性胶质母细胞瘤患者 CED 卡铂的安全性和潜在治疗效果，最终为卡铂联合放射治疗的 II 期试验提供平台。
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