en
Scientific article
English

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

Published inEuropean journal of cancer, vol. 51, no. 17, p. 2634-2642
Publication date2015-11
First online date2015-09-04
Abstract

Background: 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 < 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).

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.

eng
Keywords
  • Brain tumours
  • Chemotherapy
  • Intraventricular
  • Medulloblastoma
  • Methotrexate
  • Treatment
  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cerebellar Neoplasms / pathology
  • Cerebellar Neoplasms / therapy
  • Chemoradiotherapy
  • Child
  • Child, Preschool
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Feasibility Studies
  • Female
  • Humans
  • Infant
  • Infections / etiology
  • Injections, Intraventricular
  • Male
  • Medulloblastoma / therapy
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects
  • Multivariate Analysis
  • Neoplasm Metastasis
  • Outcome Assessment, Health Care / methods
  • Outcome Assessment, Health Care / statistics & numerical data
  • Proportional Hazards Models
  • Prospective Studies
  • Young Adult
Affiliation Not a UNIGE publication
Citation (ISO format)
POMPE, Raisa S et al. Intraventricular methotrexate as part of primary therapy for children with infant and/or metastatic medulloblastoma: Feasibility, acute toxicity and evidence for efficacy. In: European journal of cancer, 2015, vol. 51, n° 17, p. 2634–2642. doi: 10.1016/j.ejca.2015.08.009
Main files (1)
Article (Published version)
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Identifiers
ISSN of the journal0959-8049
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