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@ARTICLE{Peyrl:285006,
author = {A. Peyrl and M. Chocholous and M. Sabel and A. Lassaletta
and J. Sterba and P. Leblond and K. Nysom and I. Torsvik and
S. N. Chi and T. Perwein and N. Jones and S. Holm and P.
Nyman and H. Mörse and A. Öberg and L. Weiler-Wichtl and
U. Leiss and C. Haberler and M. T. Schmook and L. Mayr and
K. Dieckmann and M. Kool$^*$ and J. Gojo and A. A. Azizi and
N. André and M. Kieran and I. Slavc},
title = {{S}ustained {S}urvival {B}enefit in {R}ecurrent
{M}edulloblastoma by a {M}etronomic {A}ntiangiogenic
{R}egimen: {A} {N}onrandomized {C}ontrolled {T}rial.},
journal = {JAMA oncology},
volume = {9},
number = {12},
issn = {2374-2437},
address = {Chicago, Ill.},
publisher = {American Medical Association},
reportid = {DKFZ-2023-02179},
pages = {1688-1695},
year = {2023},
note = {2023 Dec 1;9(12):1688-1695},
abstract = {Medulloblastoma recurrence in patients who have previously
received irradiation has a dismal prognosis and lacks a
standard salvage regimen.To evaluate the response rate of
pediatric patients with medulloblastoma recurrence using an
antiangiogenic metronomic combinatorial approach
(Medulloblastoma European Multitarget Metronomic
Anti-Angiogenic Trial [MEMMAT]).This phase 2,
investigator-initiated, multicenter nonrandomized controlled
trial assessed 40 patients with relapsed or refractory
medulloblastoma without a ventriculoperitoneal shunt who
were younger than 20 years at original diagnosis. Patients
were enrolled between April 1, 2014, and March 31,
2021.Treatment consisted of daily oral thalidomide,
fenofibrate, celecoxib, and alternating 21-day cycles of
low-dose (metronomic) oral etoposide and cyclophosphamide,
supplemented by intravenous bevacizumab and intraventricular
therapy consisting of alternating etoposide and
cytarabine.The primary end point was response after 6 months
of antiangiogenic metronomic therapy. Secondary end points
included progression-free survival (PFS), overall survival
(OS), and quality of life. Adverse events were monitored to
assess safety.Of the 40 patients (median [range] age at
treatment start, 10 [4-17] years; 25 $[62.5\%]$ male)
prospectively enrolled, 23 $(57.5\%)$ achieved disease
control after 6 months of treatment, with a response
detected in 18 patients $(45.0\%).$ Median OS was 25.5
months (range, 10.9-40.0 months), and median PFS was 8.5
months (range, 1.7-15.4 months). Mean (SD) PFS at both 3 and
5 years was $24.6\%$ $(7.9\%),$ while mean (SD) OS at 3 and
5 years was $43.6\%$ $(8.5\%)$ and $22.6\%$ $(8.8\%),$
respectively. No significant differences in PFS or OS were
evident based on molecular subgroup analysis or the number
of prior recurrences. In patients demonstrating a response,
mean (SD) overall 5-year PFS was $49.7\%$ $(14.3\%),$ and
for patients who remained progression free for the first 12
months of treatment, mean (SD) 5-year PFS was $66.7\%$
$(16.1\%).$ Treatment was generally well tolerated. Grade 3
to 4 treatment-related adverse events included
myelosuppression, infections, seizures, and headaches. One
heavily pretreated patient with a third recurrence died of
secondary acute myeloid leukemia.This feasible and
well-tolerated MEMMAT combination regimen demonstrated
promising activity in patients with previously irradiated
recurrent medulloblastoma. Given these results, this
predominantly oral, well-tolerated, and outpatient treatment
warrants further evaluation.ClinicalTrials.gov Identifier:
NCT01356290.},
cin = {B062 / HD01},
ddc = {610},
cid = {I:(DE-He78)B062-20160331 / I:(DE-He78)HD01-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37883081},
doi = {10.1001/jamaoncol.2023.4437},
url = {https://inrepo02.dkfz.de/record/285006},
}