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Intraventricular methotrexate as part of primary therapy for children with infant and/or metastatic medulloblastoma: Feasibility, acute toxicity and evidence for efficacy.

AbstractBACKGROUND:
To assess feasibility, acute toxicity, and efficacy of intraventricular methotrexate administered as part of the primary therapy in medulloblastoma.
METHODS:
From 2001 to 2007, 240 patients <22years 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 >4years with metastatic, 59 <4years with non-metastatic, 31 <4years with metastatic medulloblastoma).
RESULTS:
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).
CONCLUSION:
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.
AuthorsRaisa S Pompe, André O von Bueren, Martin Mynarek, Katja von Hoff, Carsten Friedrich, Robert Kwiecien, Wiebke Treulieb, Christine Lindow, Frank Deinlein, Gudrun Fleischhack, Joachim Kuehl, Stefan Rutkowski
JournalEuropean journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 51 Issue 17 Pg. 2634-42 (Nov 2015) ISSN: 1879-0852 [Electronic] England
PMID26346136 (Publication Type: Journal Article)
CopyrightCopyright © 2015 Elsevier Ltd. All rights reserved.

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