Feasibility and efficacy of MEMMAT-like regimen in heavily pretreated adult patients with recurrent malignant embryonal brain tumors: A series of 6 cases.

BACKGROUND

The prognosis of adult patients with recurrent malignant embryonal brain tumors remains poor due to the lack of effective and validated treatment. A metronomic and antiangiogenic chemotherapy regimen called MEMMAT was developed in children, with promising results. Additional data on feasibility, tolerance, and efficacy in adults are necessary.

METHODS

This retrospective observational case series included adult patients with relapsing medulloblastoma (MB) or pineoblastoma (PB) treated with MEMMAT-adapted protocol. Treatment consisted of daily oral thalidomide, fenofibrate, and celecoxib, and alternating 21-day cycles of metronomic etoposide and cyclophosphamide associated with bevacizumab and personalized intraventricular chemotherapy.

RESULTS

Four SHH-activated MB and 2 PB were included. Median duration of treatment was 12 months (range 3-21). Significant partial response occurred in 2/4 MB patients and 2/2 PB. The best responses were observed on leptomeningeal lesions. Main grade 3-4 toxicity was neutropenia in all patients (no febrile neutropenia) and lymphopenia in all but one (2 opportunistic infections). Dose adjustments in chemotherapy and thalidomide for hematotoxicity were necessary in all patients within the first 3 months. Cumulative neurotoxicity from thalidomide affected the 4 patients with prolonged treatment (1 grade 3, 3 grade 2). Rechallenge was tried in PB patients and successful (duration: 9 months).

CONCLUSIONS

MEMMAT is feasible in adult patients and can lead to a significant and sustained response in recurrent malignant embryonal brain tumors. Hematotoxicity is progressive and manageable. The withdrawal of thalidomide and starting dose adjustments on chemotherapy might be discussed.