Glioblastomas are impossible to completely resect and almost always recur at the borders of the resection margin. There is no established chemotherapy regimen available to patients who recur, while systemic treatment is hampered by the blood–brain barrier. Here, we report on the first evaluation in humans of the intraparenchymal injection of irinotecan into the resection cavity after surgical resection of recurrent glioblastoma patients. The cytotoxicity of irinotecan was compared to SN-38 in primary cells from recurrent glioblastoma patients. Irinotecan was injected at multiple (~30) sites of the resection cavity wall at a depth of 3 to 5 mm. SN-38 was more cytotoxic than irinotecan at concentrations below 1 µM due to enzyme kinetics. The intraparenchymal administration of irinotecan was safe, with good wound healing and an absence of swelling, inflammation, or pseudo-abscess formation. The median survival post irinotecan administration was 32.6 weeks. The median overall survival was 30.5 months, with a two-year survival rate of 56%. This study demonstrates that local delivery of irinotecan into the brain parenchyma offers a safe route of administration over systemic delivery in the treatment of recurrent glioblastoma.
胶质母细胞瘤难以实现完全切除，且几乎总是在切除边缘复发。目前针对复发患者尚无标准化疗方案，而全身性治疗又受血脑屏障限制。本研究首次评估了复发性胶质母细胞瘤患者手术切除后，在切除腔内进行伊立替康脑实质内注射的临床效果。通过对比伊立替康与其活性代谢产物SN-38对复发性胶质母细胞瘤原代细胞的细胞毒性，发现由于酶动力学差异，在低于1 µM浓度下SN-38的细胞毒性更强。术中采用多点（约30个）注射方式，将伊立替康以3-5毫米深度注入切除腔壁。结果显示伊立替康脑实质内给药安全性良好，伤口愈合正常，未出现肿胀、炎症或假性脓肿形成。患者接受伊立替康治疗后的中位生存期为32.6周，总中位生存期达30.5个月，两年生存率为56%。本研究表明，在复发性胶质母细胞瘤治疗中，与全身给药相比，伊立替康局部脑实质内给药是一种安全有效的给药途径。
肿瘤(癌症)患者之家