Intraventricular methotrexate as part of primary therapy for children with infant and/or metastatic medulloblastoma: Feasibility, acute toxicity and evidence for efficacy
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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. / Pompe, Raisa S; von Bueren, André O; Mynarek, Martin; von Hoff, Katja; Friedrich, Carsten; Kwiecien, Robert; Treulieb, Wiebke; Lindow, Christine; Deinlein, Frank; Fleischhack, Gudrun; Kuehl, Joachim; Rutkowski, Stefan.
In: EUR J CANCER, Vol. 51, No. 17, 11.2015, p. 2634-2642.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Intraventricular methotrexate as part of primary therapy for children with infant and/or metastatic medulloblastoma: Feasibility, acute toxicity and evidence for efficacy
AU - Pompe, Raisa S
AU - von Bueren, André O
AU - Mynarek, Martin
AU - von Hoff, Katja
AU - Friedrich, Carsten
AU - Kwiecien, Robert
AU - Treulieb, Wiebke
AU - Lindow, Christine
AU - Deinlein, Frank
AU - Fleischhack, Gudrun
AU - Kuehl, Joachim
AU - Rutkowski, Stefan
N1 - Copyright © 2015 Elsevier Ltd. All rights reserved.
PY - 2015/11
Y1 - 2015/11
N2 - 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 <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.
AB - 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 <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.
U2 - 10.1016/j.ejca.2015.08.009
DO - 10.1016/j.ejca.2015.08.009
M3 - SCORING: Journal article
C2 - 26346136
VL - 51
SP - 2634
EP - 2642
JO - EUR J CANCER
JF - EUR J CANCER
SN - 0959-8049
IS - 17
ER -