Neuwelt E A, Howieson J, Frenkel E P, Specht H D, Weigel R, Buchan C G, Hill S A
Neurosurgery. 1986 Oct;19(4):573-82. doi: 10.1227/00006123-198610000-00011.
Reversible osmotic blood-brain barrier (BBB) modification was used in 38 patients with glioblastoma to enhance the delivery of chemotherapeutic agents. The patients ranged in age from 14 to 70 years (mean, 43), and all had prior surgery and radiation; 5 had also received systemic chemotherapy. Karnofsky Performance Status (KPS) scores ranged from 60 to 100% (mean, 79) on admission to the treatment program. Barrier modification was achieved by intracarotid or intravertebral artery infusion of mannitol, and a chemotherapy regimen of methotrexate, cytoxan, and procarbazine was given in conjunction with barrier modification. The 38 glioblastoma patients were compared to two control groups of patients with glioblastoma; these encompassed 14 patients treated with surgery and radiation and 8 treated with surgery, radiation, and systemic chemotherapy. Survival analysis using the Cox Proportional Hazards Regression Model (corrected for age, sex, presence or absence of necrosis, and functional status) showed that patients receiving chemotherapy with BBB modification had a statistically significant (P = 0.0006) longer expected survival (17.5 months) than the control groups (12.8 and 11.4 months, respectively). Presently 16 patients of the barrier-enhanced treatment group are alive at 5 to 42 months from diagnosis (median, 20) with KPS scores ranging from 40 to 90% (median, 65). The neurological complications seen included a stroke-like syndrome in 3 patients (1 with decreased motor movement in the hand, 1 with marked hemiparesis, and 1 with hemiplegia), transient exacerbation of preexisting neurological deficits lasting 2 to 3 days, and a 15% incidence of seizures during or within 24 hours of the BBB modification. In 2 of the 38 patients, radiographic documentation of central nervous system tumor regression concurrent with the development of new tumor nodule(s) in portions of the brain distant from the region of osmotic BBB opening was seen. These studies indicate that chemotherapeutic drug delivery to tumors (as well as surrounding brain) can be augmented by osmotic BBB modification and that such therapy can result in a prolongation of survival.
38例胶质母细胞瘤患者采用可逆性渗透血脑屏障（BBB）修饰术来增强化疗药物的递送。患者年龄在14至70岁之间（平均43岁），均曾接受过手术和放疗；5例还接受过全身化疗。入组治疗时，卡诺夫斯基功能状态（KPS）评分在60%至100%之间（平均79%）。通过颈内动脉或椎动脉输注甘露醇实现屏障修饰，并在屏障修饰的同时给予甲氨蝶呤、环磷酰胺和丙卡巴肼的化疗方案。将这38例胶质母细胞瘤患者与两组胶质母细胞瘤对照患者进行比较；对照组包括14例接受手术和放疗的患者以及8例接受手术、放疗和全身化疗的患者。使用Cox比例风险回归模型进行生存分析（校正年龄、性别、有无坏死及功能状态）显示，接受BBB修饰化疗的患者预期生存期（17.5个月）比对照组（分别为12.8个月和11.4个月）有统计学显著延长（P = 0.0006）。目前，屏障增强治疗组有16例患者自诊断起存活5至42个月（中位值20个月），KPS评分在40%至90%之间（中位值65%）。观察到的神经并发症包括3例患者出现类中风综合征（1例手部运动减少，1例明显偏瘫，1例偏瘫）、原有神经功能缺损短暂加重持续2至3天，以及在BBB修饰期间或24小时内癫痫发作发生率为15%。在38例患者中的2例中，可见中枢神经系统肿瘤消退的影像学记录，同时在远离渗透性BBB开放区域的脑区出现新的肿瘤结节。这些研究表明，通过渗透性BBB修饰可增强化疗药物向肿瘤（以及周围脑组织）的递送，且这种治疗可导致生存期延长。
