Medulloblastomas are the most common malignant brain tumors in children and adolescents and account for about 20 percent of all brain tumors in children. In about a quarter of cases, the tumor recurs (comes back) despite therapy with surgery, radiation and chemotherapy. For patients with previously irradiated recurrent medulloblastoma, there have been no curative treatment options. In recurrence, a medulloblastoma is almost always metastasized in the brain and thus no neurosurgical gross-total resection is possible, the tumor is resistant to conventional chemotherapeutic agents, and radiation in the brain with a tumor-effective dose is only possible once. The new therapy starves the cancer by intervening primarily in the cancer microenvironment. Until now, patients with this disease had no chance of a curative treatment.
Starting in 2006, the Department of Pediatrics and Adolescent Medicine, part of the Comprehensive Cancer Center and the Comprehensive Center for Pediatrics of MedUni Vienna and Vienna General Hospital, administered metronomic anti-angiogenic therapy to these patients. "The anti-angiogenic therapy prevents the tumor from forming blood vessels, which it needs for further growth. This therapeutic approach in the recurrent setting is attractive in that it is primarily not the tumor itself that is attacked, but the so-called “microenvironment”, and the tumor is starved", said the first author of the MEMMAT study Andreas Peyrl of the Department of Pediatrics and Adolescent Medicine, MedUni Vienna.
One quarter of patients show long-term survival of more than five years
Metronomic in this context means taking the medication daily at a low dosage so that these drugs can be given without interruption over a long period of time. The drugs used are either low-dose chemotherapeutic agents, but also drugs from other fields, such as those used in rheumatology or to lower blood lipids. Oral and intravenous therapy is augmented by intraventricular chemotherapeutics, which are injected directly into the cerebrospinal fluid. Although the children have to come to the hospital frequently, the MEMMAT combination regimen is an overall well-tolerated and out-patient treatment.
The study, initiated and funded at MedUni Vienna and now published in JAMA Oncology, involves a total of 40 patients in Austria, the Czech Republic, Spain, France, Denmark, Sweden, Norway and the USA from 2014 to 2021 and shows promising results in patients with previously irradiated medulloblastoma recurrence. One quarter of patients show long-term survival of more than five years. With previous therapies, there was only anecdotal prolonged survival in this patient group. "The results of the study are very encouraging; for the first time, we can offer these patients an effective medication," says Andreas Peyrl. In Austria, this rare form of the disease affects about three children per year. The next goal is now to evaluate this medication in a randomized study in Europe and the USA.
Publication: JAMA Oncology
Sustained Survival Benefit in Recurrent Medulloblastoma by a Metronomic Antiangiogenic Regimen. A Nonrandomized Controlled Trial.
Andreas Peyrl, Monika Chocholous, Magnus Sabel, Alvaro Lassaletta, Jaroslav Sterba, Pierre Leblond, Karsten Nysom, Ingrid Torsvik, Susan N. Chi Thomas Perwein, Neil Jones, Stefan Holm, Per Nyman, Helena Mörse, Anders Öberg, Liesa Weiler-Wichtl, Ulrike Leiss, Christine Haberler, Lisa Mayr, Karin Dieckmann, Marcel Kool, Johannes Gojo, Amedeo A. Azizi, Nicolas André, Mark Kieran and Irene Slavc.