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SHR Neuro Cancer Cardio Lipid Metab Microb

Peyrl, A; Chocholous, M; Sabel, M; Lassaletta, A; Sterba, J; Leblond, P; Nysom, K; Torsvik, I; Chi, SN; Perwein, T; Jones, N; Holm, S; Nyman, P; Mörse, H; Öberg, A; Weiler-Wichtl, L; Leiss, U; Haberler, C; Schmook, MT; Mayr, L; Dieckmann, K; Kool, M; Gojo, J; Azizi, AA; André, N; Kieran, M; Slavc, I.
Sustained Survival Benefit in Recurrent Medulloblastoma by a Metronomic Antiangiogenic Regimen: A Nonrandomized Controlled Trial.
JAMA Oncol. 2023; 9(12):1688-1695 Doi: 10.1001/jamaoncol.2023.4437 [OPEN ACCESS]
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Co-authors Med Uni Graz: Perwein Thomas
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Abstract:: IMPORTANCE: Medulloblastoma recurrence in patients who have previously received irradiation has a dismal prognosis and lacks a standard salvage regimen. OBJECTIVE: 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]). DESIGN, SETTING, AND PARTICIPANTS: 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. INTERVENTIONS: 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. MAIN OUTCOMES AND MEASURES: 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. RESULTS: 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. CONCLUSIONS AND RELEVANCE: 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. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01356290.
Find related publications in this database (using NLM MeSH Indexing): Humans - administration & dosage; Male - administration & dosage; Child - administration & dosage; Child, Preschool - administration & dosage; Adolescent - administration & dosage; Female - administration & dosage; Medulloblastoma - drug therapy, etiology; Etoposide - administration & dosage; Quality of Life - administration & dosage; Administration, Metronomic - administration & dosage; Brain Neoplasms - drug therapy; Cerebellar Neoplasms - drug therapy, etiology; Antineoplastic Combined Chemotherapy Protocols - adverse effects