Maureille Aurelien, Vauleon Enora, Meyronet David, Faure-Conter Cécile, Basle Alexandre, Larrouquere Louis, Pagnier Anne, Barritault Marc, Bonneville-Levard Alice, Leblond Pierre
Neuro-Oncology, Department of Oncology, Leon Berard Cancer Centre, Lyon, France.
Neuro-Oncology, Roger Salengro Hospital, Centre Hospitalier Régional Universitaire de Lille, Lille, France.
Neurooncol Adv. 2025 Apr 22;7(1):vdaf071. doi: 10.1093/noajnl/vdaf071. eCollection 2025 Jan-Dec.
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.
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.
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).
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.
由于缺乏有效且经过验证的治疗方法，成年复发性恶性胚胎性脑肿瘤患者的预后仍然很差。一种名为MEMMAT的节拍性抗血管生成化疗方案已在儿童中研发，取得了有前景的结果。有必要获取更多关于其在成人中的可行性、耐受性和疗效的数据。
本回顾性观察病例系列纳入了采用MEMMAT适配方案治疗的复发性髓母细胞瘤（MB）或松果体母细胞瘤（PB）成年患者。治疗包括每日口服沙利度胺、非诺贝特和塞来昔布，以及节拍性依托泊苷和环磷酰胺与贝伐单抗及个体化脑室内化疗交替进行的21天周期治疗。
纳入了4例SHH激活型MB和2例PB。中位治疗持续时间为12个月（范围3 - 21个月）。2/4的MB患者和2/2的PB患者出现显著部分缓解。在软脑膜病变中观察到最佳反应。主要的3 - 4级毒性反应为所有患者均出现中性粒细胞减少（无发热性中性粒细胞减少），除1例患者外所有患者均出现淋巴细胞减少（2例机会性感染）。所有患者在治疗的前3个月内均需要因血液毒性对化疗药物和沙利度胺进行剂量调整。沙利度胺累积神经毒性影响了4例接受延长治疗的患者（1例3级，3例2级）。对PB患者尝试重新用药并取得成功（持续时间：9个月）。
MEMMAT在成年患者中是可行的，并且可使复发性恶性胚胎性脑肿瘤产生显著且持续的反应。血液毒性是渐进性的且可控制。可能需要讨论停用沙利度胺并开始调整化疗起始剂量。
