Retrospective National “Real Life” Experience of the SFCE with the Metronomic MEMMAT and MEMMAT-like Protocol

Abstract

Background: Relapses in pediatric high-risk brain tumors remain unmet medical needs. Over the last 15 years, metronomic chemotherapy has gradually emerged as an alternative therapeutic approach. Patients and Methods: This is a national retrospective study of patients with relapsing pediatric brain tumors treated according to the MEMMAT or MEMMAT-like regimen from 2010 to 2022. Treatment consisted of daily oral thalidomide, fenofibrate, and celecoxib, and alternating 21-day cycles of metronomic etoposide and cyclophosphamide associated with bevacizumab and intraventricular chemotherapy. Results: Forty-one patients were included. The most frequent malignancies were medulloblastoma (22) and ATRT (8). Overall, the best responses were CR in eight patients (20%), PR in three patients (7%), and SD in three patients (7%), for a clinical benefit rate of 34%. The median overall survival was 26 months (IC95% = 12.4–42.7), and median EFS was 9.7 months (IC95% = 6.0–18.6). The most frequent grade ¾ toxicities were hematological. Dose had to be adjusted in 27% of the cases. There was no statistical difference in outcome between full or modified MEMMAT. The best setting seems to be when MEMMAT is used as a maintenance and at first relapse. Conclusions: The metronomic MEMMAT combination can lead to sustained control of relapsed high-risk pediatric brain tumors.

Retrospective experience of children with relapsed brain tumors treated with oral combination of axitinib and metronomic etoposide

“…5 Recently, such a multidrug metronomic regimen called MEMMAT led to sustained complete remissions of 20% pediatric patients with medulloblastoma, who all previously underwent radiotherapy as part of their treatment. 6 These findings confirmed the results of previous retrospective studies for pCNS tumors. [6][7][8] Among MC agents successfully used in the MEMMAT protocol, etoposide appears as a clinically valid option for patients with medulloblastoma and ependymoma.…”

“…6 These findings confirmed the results of previous retrospective studies for pCNS tumors. [6][7][8] Among MC agents successfully used in the MEMMAT protocol, etoposide appears as a clinically valid option for patients with medulloblastoma and ependymoma. 6 Several studies have described the clinical activity of metronomic etoposide in medulloblastoma and ependymoma.…”

Case report: Therapy-related myeloid neoplasms in three pediatric cases with medulloblastoma

“…Treatment outcomes for medulloblastoma have improved with the systematic use of chemoradiation, with a 70-80% survival rate for localized disease ( 7 ). However, therapy-related myeloid neoplasms (t-MNs) can be a potential complication of treatment for medulloblastoma ( 8 ).…”

“…There was no significant family history of malignancies. The patient received chemotherapy according to the metronomic protocol MEMMAT (etoposide and cyclophosphamide containing) ( 7 ) and focal radiotherapy (54Gy).…”

Evolution of Systemic Therapy in Medulloblastoma Including Irradiation-Sparing Approaches

“…There is an increasing interest in metronomic, low-dose chemotherapy for patients with recurrent medulloblastoma. The MEMMAT protocol has provided promising results in selected patients [82,83]. This protocol combines chemotherapy agents (cyclophosphamide, etoposide, intraventricular etoposide, and cytarabine), bevacizumab and oral thalidomide, fenofibrate and celecoxib.…”