Improved Long-Term Survival of Patients with Recurrent Medulloblastoma Treated with a "MEMMAT-like" Metronomic Antiangiogenic Approach.

Autor: Slavc I; Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.; Comprehensive Center for Pediatrics, Medical University of Vienna, 1090 Vienna, Austria., Mayr L; Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.; Comprehensive Center for Pediatrics, Medical University of Vienna, 1090 Vienna, Austria., Stepien N; Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.; Comprehensive Center for Pediatrics, Medical University of Vienna, 1090 Vienna, Austria., Gojo J; Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.; Comprehensive Center for Pediatrics, Medical University of Vienna, 1090 Vienna, Austria., Aliotti Lippolis M; Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.; Comprehensive Center for Pediatrics, Medical University of Vienna, 1090 Vienna, Austria., Azizi AA; Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.; Comprehensive Center for Pediatrics, Medical University of Vienna, 1090 Vienna, Austria., Chocholous M; Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.; Comprehensive Center for Pediatrics, Medical University of Vienna, 1090 Vienna, Austria., Baumgartner A; Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.; Comprehensive Center for Pediatrics, Medical University of Vienna, 1090 Vienna, Austria., Hedrich CS; Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.; Comprehensive Center for Pediatrics, Medical University of Vienna, 1090 Vienna, Austria., Holm S; Department of Women's and Children's Health, Karolinska Institutet, 17177 Stockholm, Sweden.; Astrid Lindgrens Children's Hospital, Karolinska University Hospital, 17164 Stockholm, Sweden., Sehested A; Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet, 2100 Copenhagen, Denmark., Leblond P; Institute of Pediatric Hematology and Oncology IHOPe, Léon Bérard Cancer Center, 69002 Lyon, France.; Department of Pediatric Oncology, Oscar Lambret Cancer Center, 59000 Lille, France., Dieckmann K; Radiation Oncology, Department of Radiotherapy, Medical University Vienna, 1090 Vienna, Austria., Haberler C; Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria., Czech T; Department of Neurosurgery, Medical University of Vienna, 1090 Vienna, Austria., Kool M; Hopp Children's Cancer Center (KiTZ), 69120 Heidelberg, Germany.; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), 69120 Heidelberg, Germany.; Princess Máxima Center for Pediatric Oncology, 3584 Utrecht, The Netherlands., Peyrl A; Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.; Comprehensive Center for Pediatrics, Medical University of Vienna, 1090 Vienna, Austria.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2022 Oct 19; Vol. 14 (20). Date of Electronic Publication: 2022 Oct 19.
DOI: 10.3390/cancers14205128
Abstrakt: Medulloblastoma (MB) recurrence is usually incurable despite intensive therapy including high-dose chemotherapy. An evolving alternative approach to conventional chemotherapy aims at interfering with tumor angiogenesis at different levels. We report on a novel combinatorial metronomic antiangiogenic approach. The study is a retrospective observational study of 29 consecutive patients with first or multiple recurrences prospectively treated according to the MEMMAT strategy ("MEMMAT-like") before the formal protocol (MEMMAT; ClinicalTrials.gov Identifier: NCT01356290) started. The study period was 11/2006 to 06/2016. Treatment consisted of daily oral thalidomide, fenofibrate, celecoxib, and alternating 21-day cycles of low-dose oral etoposide and cyclophosphamide supplemented by IV bevacizumab and intraventricular therapy consisting of alternating etoposide and liposomal cytarabine. Median overall survival (OS) after recurrence for the whole group was 29.5 months, OS was 48.3 ± 9.3% at three years and 34.5 ± 8.8% at five years, and progression-free survival was 42.0 ± 9.5% at three years and 29.4 ± 9% at five years. As of 07/2022, 9/29 patients are alive 86 to 164 months after the recurrence that prompted the "MEMMAT-like" therapy. Treatment was primarily out-patient and generally well-tolerated. Toxicities did occur but were manageable. In conclusion, antiangiogenic therapy according to the MEMMAT strategy increased median OS of patients with recurrent MB and may lead to long-term survival. Adherence to the protocol, including intraventricular therapy, appears important.
Databáze: MEDLINE
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