Jahnke Kristoph, Kraemer Dale F, Knight Kristin R, Fortin David, Bell Susan, Doolittle Nancy D, Muldoon Leslie L, Neuwelt Edward A
Department of Neurology, Oregon Health & Science University, Portland, Oregon 97239-3098, USA.
Cancer. 2008 Feb 1;112(3):581-8. doi: 10.1002/cncr.23221.
The rate of durable responses in embryonal and certain germ cell tumors of the central nervous system (CNS) is unsatisfactory. Intraarterial chemotherapy and osmotic blood-brain barrier disruption (IA/BBBD) increases drug delivery to the CNS.
Data of patients treated with carboplatin or methotrexate-based IA/BBBD on prospective phase 2 trials conducted at 3 centers were collected. Study outcomes included overall survival (OS), time to progression (TTP), and toxicity.
Fifty-four patients were treated. Twenty-seven patients received IA/BBBD as salvage treatment. The median OS was 2.8 years for all patients, 2.5 years for supratentorial and disseminated primitive neuroectodermal tumors (PNETs, n = 29), 1.7 years for medulloblastomas (n = 12), and 5.4 years for germ cell tumors (n = 13). OS and TTP for all patients were better with a Karnofsky Performance Status > or =70% (P = .0013 and .0070) and IA/BBBD as first-line treatment (P = .0059 and .029). In PNETs, OS was higher with pineal location (P = .045) and IA/BBBD as first-line treatment (P = .0036), and TTP was improved with radiotherapy before IA/BBBD (P = .036) and IA/BBBD as first-line treatment (P = .0079). Seventeen of 54 patients (31%) are alive, and 16 are alive at 4+ to 18+ years. Three survivors were not treated with radiotherapy and 4 were treated with focal radiotherapy only. The patients who were not irradiated did not develop dementia.
Survival and toxicity data appear promising, considering the cohort's adverse prognostic profile. A plateau in survival curves suggests a cure for some patients. Long-term survival may be achieved with focal or reduced-dose radiotherapy in some IA/BBBD patients.
中枢神经系统（CNS）胚胎性及某些生殖细胞肿瘤的持久缓解率并不理想。动脉内化疗联合渗透性血脑屏障破坏（IA/BBBD）可增加药物向中枢神经系统的递送。
收集在3个中心进行的前瞻性2期试验中接受基于卡铂或甲氨蝶呤的IA/BBBD治疗的患者数据。研究结局包括总生存期（OS）、疾病进展时间（TTP）和毒性。
共治疗54例患者。27例患者接受IA/BBBD作为挽救治疗。所有患者的中位OS为2.8年，幕上及播散性原始神经外胚层肿瘤（PNET，n = 29）为2.5年，髓母细胞瘤（n = 12）为1.7年，生殖细胞肿瘤（n = 13）为5.4年。卡氏功能状态评分>或=70%（P = 0.0013和0.0070）以及IA/BBBD作为一线治疗时（P = 0.0059和0.029），所有患者的OS和TTP均更佳。在PNET中，松果体部位（P = 0.045）以及IA/BBBD作为一线治疗时（P = 0.0036）OS更高，IA/BBBD前接受放疗（P = 0.036）以及IA/BBBD作为一线治疗时（P = 0.0079）TTP得到改善。54例患者中有17例（31%）存活，16例在4年至18年以上存活。3例幸存者未接受放疗，4例仅接受局部放疗。未接受放疗的患者未发生痴呆。
考虑到该队列不良的预后特征，生存和毒性数据似乎很有前景。生存曲线的平台期表明部分患者可治愈。部分接受IA/BBBD治疗的患者通过局部或减量放疗可能实现长期生存。
