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Abstract BACKGROUND Standard salvage regimen for medulloblastoma’s relapse is currently lacking. An evolving alternative approach is metronomic chemotherapy, which aims to interfere with tumor angiogenesis. We report our experience on a modified combinatorial metronomic chemotherapic/antiangiogenic approach, the Medulloblastoma European Multitarget Metronomic Anti-Angiogenic Trial (MEMMAT) regimen. Our study aimed to test efficacy and tolerance of that approach in pediatric patients with relapsed/refractory medulloblastoma treated in outpatient unit. METHODS The study was conducted from January 2017 to December 2022 at Bambino Gesù Children’s Hospital in Rome. MEMMAT-like regimen consisted of daily oral thalidomide, fenofibrate, celecoxib, and alternating 21-day cycles of low-dose oral etoposide and cyclophosphamide supplemented by intravenous bevacizumab and intrathecal topotecan. RESULTS Fourteen patients met the eligibility criteria. At diagnosis, six patients (43%) presented a localized disease, the other eight patients (57%) metastatic one; eight patients had the first recurrence and six had multiple recurrences at the start of MEMMAT-like therapy. At relapse, all the recurrences had a metastatic pattern. Methylation profiling classification showed three subgroups 3, six subgroups 4, three with SHH subgroup, and two WNT. The median overall survival after the recurrence that prompted to the use of MEMMAT like regimen, for the whole group, was 17,9 months (range, 8-32 months), with 79% (60%,100%) at 12 months and 19% (5,7%-64%) at 24 months; the mean progression-free survival (PFS) at 12 and 24 months was 57% (36%-90%) and 26% (10%-66%). When the one-year PFS rate was evaluated according to the MEMMAT-like number of treatment lines (after the first relapse or third and beyond), we found respectively 62% (37%-100%) and 50% (22%100%). CONCLUSIONS The metronomic outpatient MEMMAT-like combination is feasible, well tolerated, and can lead to sustained control of relapse in medulloblastoma. The best setting seems to be after the first relapse to achieve a higher PFS.
Cacchione et al. (Tue,) studied this question.