P14.16 Complete sustaining radiological response of a multi-recurrent disseminated adult medulloblastoma after antiangiogenic metronomic combined pediatric regimen MEMMAT: a case report
Authors: Duran-Peña A , Garcilazo-Reyes Y , Frappaz D , Feuvret L , Bielle F , Capelle L , Savatovsky J , Laigle-Donadey F 
Published: September 2019

Abstract

BACKGROUND
Even if medulloblastoma is considered as a curable disease, recurrent medulloblastoma has a poor prognosis, independently of therapy used. Medulloblastoma is very rare in adults, unlike children, and therapeutic strategies at recurrence are lacking. Nevertheless, adult teams sometimes use as “compassionate” chemotherapy some regimens published in children, such as the MEMMAT metronomic combination. However, this treatment, targeting both endothelial and proliferating tumor cells, has to date not been studied in the adult population.

MATERIAL AND METHODS
We present the case of a 40-year-old man, suffering from a right cerebellar SHH mutated medulloblastoma initially diagnosed and treated in 2014 by craniospinal radiotherapy associated with 4 cycles of carboplatine-VP16 following complete resection. Since April 2016, date of first relapse, numerous successive recurrences occurred, initially focal, treated by several surgeries (April and November 2016, January 2017), chemotherapy (rechallenge by carboplatine-VP16) then stereotactic radiotherapy. He then developed in October 2017 a new relapse in the posterior fossa, also associated with a meningeal dissemination on lumbar MRI. IK was 90%. He was then treated by TOTEM regimen (Temozolomide-Topotecan) followed by “Packer” regimen (Cisplatin-Belustine-Vincristin), without tumor control. However, because patient was non symptomatic with a KPS of 80%, we decided, according to the AJA French group, to propose what we presumed to be a “compassionate” chemotherapy, by metronomic pediatric regimen “MEMMAT”. For “supportive care” reasons, we decided not to realize the “Intrathecal part” of this regimen and administered to the patient intravenous bevacizumab (10 mg/kg d1-d14-d21), thalidomide (100 mg/d), celecoxib (300 mg bid), fenofibrate (160 mg/d) and etoposide (100 mg/d d1-21), alternating with cyclophosphamide (100 mg/d d22-42).

RESULTS
Clinical tolerance was very good, except grade 1 heel pain and fatigue; hematological toxicity was mild (transient grade 3 neutropenia, grade 4 lymphopenia); renal impairment, already present at the beginning, was increasing, and justified dose adjustment after 5 cycles and nephrologic explorations, ongoing. Radiological evaluation showed a complete radiological response with complete disappearance of enhancing lesions on first MRIs realized after 3 months (2 cycles); this response was confirmed after 6 months (4 cycles) and 9 months (6 cycles) on both cerebral and spinal MRI. Patient is now receiving the 7th cycle.

CONCLUSION
We report here the first case of a complete and sustaining response of an adult multi-recurrent metastatic medulloblastoma treated by a pediatric antiangiogenic metronomic regimen “MEMMAT”. This promising result incites to develop a dedicated prospective trial in adults in view to confirm the interest of this strategy.