Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Germany.
Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Germany; Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, University Medical Center Goettingen, Germany.
Eur J Cancer. 2015 Nov;51(17):2634-42. doi: 10.1016/j.ejca.2015.08.009. Epub 2015 Sep 4.
To assess feasibility, acute toxicity, and efficacy of intraventricular methotrexate administered as part of the primary therapy in medulloblastoma.
From 2001 to 2007, 240 patients < 22 years from 61 treatment centres were registered. Patients received 2-3 cycles of intraventricular methotrexate with systemic chemotherapy in three different treatment arms of the prospective multicentre trial HIT2000 (150 children > 4 years with metastatic, 59 < 4 years with non-metastatic, 31 < 4 years with metastatic medulloblastoma).
211 patients received an intraventricular access device with a subcutaneous reservoir for the application of chemotherapy. Reservoir-associated complications were documented in 57 (27%) patients, mostly due to infection (n = 32) and reservoir malfunction (n = 19), requiring removal in 39 (18%) patients. Acute neurotoxicity likely associated with intraventricular MTX was observed in 9/202 documented patients. Toxicity was usually mild, apart from one therapy-associated death due to toxic oedema followed by seizures. Of 519 treatment cycles including intraventricular methotrexate, 226 (43%) were reduced or omitted, most frequently due to the absence of an intraventricular device. Survival rates were higher in patients receiving ⩾ 75% of the scheduled intraventricular methotrexate dose compared to those receiving < 75% in both univariate and multivariate models (event-free survival (EFS), 61.5 versus 46.2%, p = 0.004; OS, 75.5% versus 60.4%, p = 0.015; hazard ratio: EFS 1.723, p = 0.016; OS 1.648, p = 0.051).
Intraventricular methotrexate therapy was feasible and mostly well tolerated. Infections were the most frequent complication. A higher cumulative dose of intraventricular methotrexate was associated with better survival. Further evaluation of efficacy and late effects is warranted.
评估甲氨蝶呤（MTX）鞘内注射作为髓母细胞瘤一线治疗方案的可行性、急性毒性和疗效。
2001 年至 2007 年，来自 61 个治疗中心的 240 名<22 岁的患者被纳入研究。患者接受 2-3 个周期的鞘内 MTX 联合全身化疗，该研究为前瞻性多中心 HIT2000 试验的三个不同治疗臂之一，其中 150 名年龄>4 岁的转移性患儿、59 名<4 岁的非转移性患儿和 31 名<4 岁的转移性髓母细胞瘤患儿接受治疗。
211 名患者接受了带皮下储液器的鞘内给药装置，用于化疗药物的输注。57 名（27%）患者出现与储液器相关的并发症，主要是由于感染（n=32）和储液器功能障碍（n=19），其中 39 名（18%）患者需要将储液器取出。202 名接受鞘内 MTX 治疗的患者中，有 9 名出现可能与鞘内 MTX 相关的急性神经毒性，毒性通常较轻，只有 1 例因毒性水肿导致癫痫发作而死亡。519 个治疗周期中，226 个（43%）被减少或省略，最常见的原因是没有鞘内给药装置。在单变量和多变量模型中，接受≥75%计划鞘内 MTX 剂量的患者的生存率高于接受<75%剂量的患者（无事件生存率（EFS）：61.5%比 46.2%，p=0.004；总生存率（OS）：75.5%比 60.4%，p=0.015；风险比：EFS 1.723，p=0.016；OS 1.648，p=0.051）。
鞘内 MTX 治疗是可行的，且大多数患者耐受良好。感染是最常见的并发症。较高的累积剂量与更好的生存相关。需要进一步评估疗效和晚期效应。
