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

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 <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).
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.
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.

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: