Metronomics Global Health Initiative

Real-life experience with a "modified-MEMMAT" regimen for relapsed medulloblastoma

Nicolas André — 2026-02-24T15:47:28Z

Thus a retrospective work lead by the Bambino Gesù Children's Hospital in Roma evaluating MEMMAT like combinations in medulloblastoma. The article is entitled : Experience with a "modified-MEMMAT" regimen for relapsed medulloblastoma and has been published in Ther Adv Med Oncol.

The authors (Antonella Cacchione, Giada Del Baldo, Federica D'Antonio, Valentina Di Ruscio , Giacomina Megaro, Chiara Pilotto, Assunta Tornesello, Alessandro Cocciolo, Sabina Vennarini, Silvia Chiesa, Andrea Carai, Andrea De Salvo, Giulia Albino, Giovanna Stefania Colafati, Irene Slavc, Angela Mastronuzzi from the Bambino Gesù Children's Hospital, the Sapienza University of Rome, the ASUFC Santa Maria Della Misericordia, Udine, the Ospedale Vito Fazzi, Lecce, the Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Ithe Fondazione Policlinico Universitario "A. Gemelli," Catholic University of Sacred Heart, Rome,
the Medical University of Vienna, Austria confirm the promising antitumorali activity of the combination.

Background: Medulloblastoma (MB) relapse is typically resistant to available treatments. An emerging alternative strategy focuses on disrupting tumor angiogenesis at various stages, using a combined metronomic anti-angiogenic approach.

Objectives: The study aims to assess the efficacy and safety of this modified treatment approach in managing recurrent MB in the pediatric population.

Designs: This study is a retrospective observational analysis involving 14 pediatric patients diagnosed with first or multiple recurrences of MB.

Methods: We analyzed clinical, molecular, radiological, and outcome data of our cohort treated using a modified Medulloblastoma European Multitarget Metronomic Anti-Angiogenic Trial (MEMMAT) strategy.

Results: Median age of patients was 11.6 years (range: 6.4-26 years). All 14 patients presented with a metastatic relapse after conventional treatments. The median time from primary diagnosis/prior relapse to the start of "modified MEMMAT" was 22 months (range: 2-60 months). Fifty-seven percent received the "modified MEMMAT" schema as second-line treatment, while 43% received it as third-line or beyond after recurrence. At a median follow-up of 17.9 months, the median overall survival (OS) from the MEMMAT start date was 18.2 months, and the median progression-free survival (PFS) was 12.8 months. OS at 12 and 24 months was 78.6% and 28.6%, respectively. PFS at 6 and 12 months was 100% and 55.0%, respectively. Treatment was globally well tolerated.

Conclusion: The modified MEMMAT strategy shows promise in treating recurrent MB, achieving a 12-month OS rate from date of starting treatment of 78.6%, with manageable toxicity. These findings suggest its potential as a viable option for heavily pre-treated pediatric patients, warranting further validation in larger prospective studies.

you can read the full paper here :

Results of the Latin American Pediatric Oncology Group (GALOP) Trial for Patients With Metastatic Ewing Sarcoma: Multicentric Study of Interval-Compressed Multiagent and Metronomic Chemotherapy

Nicolas André — 2025-07-29T07:59:03Z

Adriana Rose , Lauro Jose Gregianin , Erica Boldrini , Carla Macedo , Sima Ferman , Tatiana El Jaick Bonifácio Costa , Marcelo Scopinaro , Algemir Lunardi Brunetto , André Tesainer Brunetto , Milena Villarroel on behalf of the GALOP Latin American Pediatric Oncology Group Ewing Sarcoma Investigators have published in Pediatric Blood and Cancer the result from an internaytional clinical trial entitled: Results of the Latin American Pediatric Oncology Group (GALOP) Trial for Patients With Metastatic Ewing Sarcoma: Multicentric Study of Interval-Compressed Multiagent and Metronomic Chemotherapy.

the full text of the paper can be foundhere

Abstract
Background: GALOP investigators developed a multicenter protocol to standardize treatment for newly diagnosed metastatic Ewing sarcoma (ES) in South America.

Methods: Prospective trial. Induction chemotherapy consisted of 9 alternating interval-compressed cycles (every 14 days) of vincristine, doxorubicin, cyclophosphamide, and ifosfamide-etoposide; local and metastatic site control; and 5 consolidation cycles (every 21 days), followed by MCT with cyclophosphamide and vinblastine for 1 year.

Results: Between 2011 and 2019, 198 patients were recruited from 34 centers in Argentina, Brazil, Chile, and Uruguay. Characteristics include: male patients (60.6%), median age of 12.3 years (range, 0.8-31.1); axial primary localization (62.1%), size >8 cm (70.2%); and bone origin (71.2%). Metastatic sites were lung, extra-lung, and combined in 43.4%, 31.3%, and 25.3%, respectively. The overall response rate was 79.3%, and local treatment was performed in 85.3% of patients. With a median follow-up of 65.1 months (95% CI: 53.9-76.4), the 5-year overall survival (OS) and event-free survival (EFS) were 33.1% (95% CI: 25.9-40.4) and 27.8% (95% CI: 21.5-34.3), respectively. The 5-year OS was 44.9%, 31.3%, and 15.6% for lung, extra-lung, and combined, respectively (p < 0.001). The median interval between induction chemotherapy cycles was 17 days, with a febrile neutropenia rate of 19.3%. Metronomic chemotherapy (MCT) was administered to 100 patients (50.5%), demonstrating good tolerability, with 58 patients completing at least 75% of the scheduled cycles.

Conclusion: The implementation of a multicenter protocol incorporating MCT for metastatic ES proved feasible across Latin America.

Myelodysplastic syndrome-post-cytotoxic therapy for pediatric low-grade glioma

Nicolas André — 2025-07-29T07:43:09Z

A case report entitled : Myelodysplastic syndrome-post-cytotoxic therapy for pediatric low-grade glioma authored by Phoebe Power, Susannah Payne, Rebecca Walsh, Adam Nelson & Neevika Manoharan from Department of Pediatric Oncology, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, USA and Kids Cancer Centre, Sydney Children's Hospital, Australia has been published in Child's Nervous System

The full text is freely avaliable here

Abstract

Myeloid neoplasms-post cytotoxic therapy (MN-pCT, previously therapy-related myeloid neoplasms/tMN), are secondary malignancies associated with prior chemotherapy treatment, historically carrying a very poor prognosis. These are rarely associated with primary central nervous system (CNS) tumors, usually high-grade CNS malignancies requiring intensive multimodal treatment. Pediatric low-grade gliomas (pLGGs) are the most common childhood CNS tumors, and up to 50% of patients will require adjuvant therapy, which has traditionally consisted of low-dose metronomic chemotherapy, though the recent identification of key molecular drivers of pLGG means targeted therapies are changing this paradigm. We present a novel case of a 17-year-old girl with therapy-related myelodysplastic syndrome following chemotherapeutic treatment for pLGG. Given the poor prognosis of MN-pCTs, this case represents an important note of caution when choosing appropriate therapy for pLGG, especially considering the evolving role for targeted treatments in this disease.

Infantile myofibromatosis: Small bumps pose big problems

2025-03-25T10:17:14Z

Hillary C Lee, Amee A Amin, Kudakwashe R Chikwava, Valeria R Smith, and Caraciolo J Fernandes from
the Section of Neonatal-Perinatal Medicine, Department of Pediatrics, the Department of Pathology and Immunology, and the Division of Hematology and Oncology, Department of Pediatrics, Baylor College of Medicine/Texas Children's Hospital, Houston, TX, USA.
have just published in Neonatal Perinatal Medicine a brief report entitled :
Infantile myofibromatosis: Small bumps pose big problems

It reports about a preterm, male infant with a trichorionic, triamniotic pregnancy following preterm labor. Within the first week of life, several well-circumscribed, smooth, non-tender, and soft nodules with some mobility were noticed along the border of the ribs, across the trunk, back, and lower extremities. Ultrasound imaging confirmed well-circumscribed hypoechoic, intramuscular nodules, and biopsy evaluation showed atypical spindle cell proliferation. The biopsied lesion was PDGFRB-mutated on molecular genetic studies, confirming a diagnosis of myofibromatosis. The infant developed mixed lytic and sclerotic deformities of a variety of bones, necessitating treatment given disease progression.

Infantile myofibromatosis is characterized by proliferation of benign myofibroblastic tumors that typically manifest as solitary or multiple nodules in the skin, muscle, bone, subcutaneous tissues, and visceral organs and can pose significant morbidity and mortality risks, particularly in cases involving visceral organs or causing functional impairment. These soft tissue lesions are the most prevalent benign fibrous tumors that present before age two and can undergo spontaneous regression or are amenable to surgical resection.

Conclusion: Successful clinical management with low-dose metronomic chemotherapy (methotrexate and vinblastine) is possible and can treat extensive disease, as seen in our patient.

The full text of the article is available here

Evolution and contemporary role of metronomic chemotherapy in the treatment of neuroblastoma

2024-05-07T06:46:14Z

As part of a "metronomics" special issue in "Cancer Letters", Shu-Wei Chou and Hsiu-Hao Chang from the Department of Pediatrics, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan have just published a review entitled : Evolution and contemporary role of metronomic chemotherapy in the treatment of neuroblastoma

Abstract

Metronomic chemotherapy refers to the consistent and regular administration of low-dose chemotherapeutic agents over an extended period, with minimal or no extended drug-free intervals. The effectiveness of metronomic chemotherapy is derived from its capacity to impede tumor angiogenesis and foster antitumor immune responses, rather than merely interrupting tumor cell mitosis. Metronomic chemotherapy has been applied in the treatment of neuroblastoma for decades, including patients with newly diagnosed high-risk neuroblastoma and relapsed or refractory neuroblastoma. In the modern era of neuroblastoma treatment, metronomic chemotherapy remains a viable option for maintenance therapy in newly diagnosed neuroblastoma patients without access to autologous stem cell transplantation or immunotherapy, especially in resource-limited regions. For relapsed or refractory patients, metronomic chemotherapy is a suitable alternative for individuals intolerant to intensified treatments or receiving palliative care. Cyclophosphamide, etoposide, vinca alkaloids, and celecoxib constitute the primary components of current metronomic chemotherapy. Given the need for additional research to determine the optimal regimen, comprehensive studies must be conducted to explore and establish standardized metronomic chemotherapy protocols. Additionally, investigating potential biomarkers and clinical prognostic factors is imperative for future advancements in this field.

The full text can be found here.

Metronomic Chemotherapy for Pediatric Refractory Solid Tumors: A Retrospective Single-Center Study

2024-05-07T06:24:44Z

In the last issue of the J Pediatr Hematol Oncol, Yukari Sakurai, Fuminori Iwasaki, Ayana Hirose, Naoya Matsumoto, Naoyuki Miyagawa, Dai Keino, Tomoko Yokosuka, Satoshi Hamanoue, Masakatsu Yanagimachi, Masae Shiomi, Shoko Goto, Mio Tanaka , Yukichi Tanaka, Kumiko Nozawa, Hiroaki Goto from the divisions of Division of Hematology/Oncology, of Pathology and of Radiology of the Children's Medical Center Yokohama, Japan have just published an original article entitled : Metronomic Chemotherapy for Pediatric Refractory Solid Tumors: A Retrospective Single-Center Study. reporting their monocentric experience

Abstract

Metronomic chemotherapy (MC) is based on chronic administration of chemotherapeutic agents at minimally toxic doses without prolonged drug-free breaks, that inhibits tumor angiogenesis and induces tumor dormancy. This study aimed to determine the efficacy of MC for pediatric refractory solid tumors. We retrospectively analyzed the data of pediatric patients with relapsed/refractory solid tumors who received treatment, including low-dose continuous administration of anticancer drugs, at our institute. Of the 18 patients, the disease statuses at the initiation of MC were complete remission (n=2), partial remission/stable disease (n=5), and progressive disease (n=11). The overall survival rate was 61% at 12 months and 34% at 24 months, and the progression-free survival rate was 21% at 12 and 24 months. Although only 5 of the 18 patients showed certain tumor regression or maintained remission, tumors that stabilized, maintained remission/stable disease, and showed certain advantages in terms of overall survival rate, even if limited to progressive disease. Approximately half of the patients demonstrated temporal tumor stabilization and improved survival time. Overall, previous reports and the present study support the conclusion that MC has the potential to play an important role in pediatric cancer treatment during the advanced stage.

the full text can be found here

Sustained Survival Benefit in Recurrent Medulloblastoma by a Metronomic Antiangiogenic Regimen A Nonrandomized Controlled Trial

2023-11-15T08:10:16Z

We are very excited to share the final results of the MEMMAT trial for the medullobastoma cohort- a gamme changer ! The results have been published by the JAMA Oncology journal. The article is entitled : Sustained Survival Benefit in Recurrent Medulloblastoma by a Metronomic Antiangiogenic Regimen A Nonrandomized Controlled Trial
MGHI is very proud to be part of this work.

Andreas Peyrl; Monika Chocholous ; Magnus Sabel ; Alvaro Lassaletta ; Jaroslav Sterba; Pierre Leblond; Karsten Nysom; Ingrid Torsvik ; Susan N. Chi; Thomas Perwein; Neil Jones; Stefan Holm; Per Nyman; Helena Mörse; Anders Öberg; Liesa Weiler-Wichtl; Ulrike Leiss; Christine Haberler; Maresa T. Schmook; Lisa Mayr; Karin Dieckmann; Marcel Kool; Johannes Gojo; Amedeo A. Azizi; Nicolas André; Mark Kieran; Irene Slavc

from the :
1Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria
2Comprehensive Center for Pediatrics, Medical University of Vienna, Vienna, Austria
3Childhood Cancer Centre, Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden
4Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
5Department of Pediatric Neuro-Oncology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
6Pediatric Oncology Department, University Hospital Brno, Brno, Czech Republic
7Pediatric Oncology Unit, Oscar Lambret Comprehensive Cancer Center, Lille, France
8Centre Léon Bérard, Institut d'Hématologie et d'Oncologie Pediatrique, Lyon, France
9Department of Paediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark
10Department of Paediatric and Adolescent Medicine, Haukeland University Hospital, Bergen, Norway
11Department of Pediatric Neuro-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts
12Division of Pediatric Hemato-Oncology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria
13Kinderonkologie, Salzburger Universitätsklinikum, Salzburg, Austria
14Department of Pediatric Hematology and Oncology, Karolinska University Hospital, Stockholm, Sweden
15Department of Paediatrics, Linköping University Hospital, Linköping, Sweden
16Pediatric Cancer Center, Skane University Hospital, Lund, Sweden
17Department of Pediatrics, Uppsala University, Uppsala, Sweden
18Department of Neurology, Medical University of Vienna, Vienna, Austria
19Department of Biomedical Imaging and Image-Guided Therapy, Division of Neuroradiology and Musculoskeletal Radiology, Medical University of Vienna, Vienna, Austria
20Department of Radio-Oncology, Medical University of Vienna, Vienna, Austria
21Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany
22Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany
23Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
24Départment of Pediatric Oncology, Assistance Publique-Hopitaux de Marseille, Marseille, France
25Aix Marseille University, Cancer Research Center of Marseille, Marseille, France

Abstract

Importance Medulloblastoma recurrence in patients who have previously received irradiation has a dismal prognosis and lacks a standard salvage regimen.

Objective: To evaluate the response rate of pediatric patients with medulloblastoma recurrence using an antiangiogenic metronomic combinatorial approach (Medulloblastoma European Multitarget Metronomic Anti-Angiogenic Trial [MEMMAT]).

Design, Setting, and Participants: This phase 2, investigator-initiated, multicenter nonrandomized controlled trial assessed 40 patients with relapsed or refractory medulloblastoma without a ventriculoperitoneal shunt who were younger than 20 years at original diagnosis. Patients were enrolled between April 1, 2014, and March 31, 2021.

Interventions: Treatment consisted of daily oral thalidomide, fenofibrate, celecoxib, and alternating 21-day cycles of low-dose (metronomic) oral etoposide and cyclophosphamide, supplemented by intravenous bevacizumab and intraventricular therapy consisting of alternating etoposide and cytarabine.

Main Outcomes and Measures: The primary end point was response after 6 months of antiangiogenic metronomic therapy. Secondary end points included progression-free survival (PFS), overall survival (OS), and quality of life. Adverse events were monitored to assess safety.

Results: Of the 40 patients (median [range] age at treatment start, 10 [4-17] years; 25 [62.5%] male) prospectively enrolled, 23 (57.5%) achieved disease control after 6 months of treatment, with a response detected in 18 patients (45.0%). Median OS was 25.5 months (range, 10.9-40.0 months), and median PFS was 8.5 months (range, 1.7-15.4 months). Mean (SD) PFS at both 3 and 5 years was 24.6% (7.9%), while mean (SD) OS at 3 and 5 years was 43.6% (8.5%) and 22.6% (8.8%), respectively. No significant differences in PFS or OS were evident based on molecular subgroup analysis or the number of prior recurrences. In patients demonstrating a response, mean (SD) overall 5-year PFS was 49.7% (14.3%), and for patients who remained progression free for the first 12 months of treatment, mean (SD) 5-year PFS was 66.7% (16.1%). Treatment was generally well tolerated. Grade 3 to 4 treatment-related adverse events included myelosuppression, infections, seizures, and headaches. One heavily pretreated patient with a third recurrence died of secondary acute myeloid leukemia.

Conclusions and Relevance: This feasible and well-tolerated MEMMAT combination regimen demonstrated promising activity in patients with previously irradiated recurrent medulloblastoma. Given these results, this predominantly oral, well-tolerated, and outpatient treatment warrants further evaluation.

the full text of the article is freely available here.

Effectiveness of metronomic chemotherapy in a child with medulloblastoma: A case report

2023-04-04T09:09:45Z

Elena Lygina Daria Morgacheva Avinash Khadela Humzah Postwala Yesha Shah Yulia Dinikina
from the Department of Chemotherapy for Hematologic Diseases and Bone Marrow Transplantation for Children, Almazov National Medical Research Centre, St. Petersburg, Russia, Department of Pharmacology, L.M. College of Pharmacy, Navrangpura, Ahmedabad, Gujarat 380009, India, Pharm D Section, L.M. College of Pharmacy, Navrangpura, Ahmedabad, Gujarat, India have published in Oncology letters a case report entitled: Effectiveness of metronomic chemotherapy in a child with medulloblastoma: A case report

Medulloblastoma (MB) is one of the most common pediatric malignant tumors arising from the central nervous system with an unknown etiology and variable prognosis. Relapsed or refractory MB in pediatric patients after intensive anticancer therapy (chemo‑, radiotherapy) is associated with treatment resistance and poor survival prognosis. Metronomic chemotherapy in combination with mTOR inhibitors may have advantages due to an alternate mechanism of cytotoxicity and a favourable adverse effects profile. Furthermore, it is considered to be a prospective anticancer regimen regardless of the presence/absence of molecular targets. The present study reported a successful result of this treatment option with optimal tolerability in relapsed MB in a pediatric male patient and highlighted the advantages for a selected group of patients.

You can have access to the free full text here

Metronomic Chemotherapy in Pediatric Oncology: From Preclinical Evidence to Clinical Studies

2022-11-09T14:18:04Z

As part of a special issue entitled: [Clinical Applications of Metronomic Chemotherapy in the Journal of Clinical Medicine , Banchi M, Fini E, Crucitta S, Bocci G from the Department of Clinical and Experimental Medicine, University of Pisa, VItaly have just published a review article : Metronomic Chemotherapy in Pediatric Oncology: From Preclinical Evidence to Clinical Studies.
The full text is freely available here.

Abstract

Metronomic chemotherapy (MC) is the frequent, regular administration of drug doses designed to maintain a low, but active, range of concentrations of chemotherapeutic drugs, during prolonged periods of time without inducing excessive toxicities. To date, more than 400,000 children and adolescents under the age of 20 are diagnosed with cancer, per year, with 80% survival in most high-income countries, but less than 30% in low- and middle-income ones. In this review, we summarized the principal preclinical and clinical studies involving the use of MC in the most common pediatric tumors, with an overview of efficacy, toxicity, pharmacokinetic profile, and biomarkers. The best advantages of MC are low toxicity, oral administration and, thus, the feasibility of a more comfortable, home-based treatment, therefore improving the quality of life of the children themselves and of their parents and caregivers. Moreover, MC could represent a valid method to reduce the economic burden of anticancer therapy in the pediatric setting

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

2022-10-20T11:05:14Z

Irene Slavc, Lisa Mayr, Natalia Stepien, Johannes Gojo, Maria Aliotti Lippolis, Amedeo A. Azizi, Monika Chocholous, Alicia Baumgartner,Cora S. Hedrich, Stefan Holm, Astrid Sehested, Pierre Leblond, Karin Dieckmann, Christine Haberler,Thomas Czech, Marcel Kool and Andreas Peyrl from the Medical University of Vienna, Austria, tthe Karolinska University Hospital, Sweden, the Copenhagen University Hospital Rigshospitalet, Denmark and teh Oscar Lambret Cancer Center, Lille, France have just published in Cancers and article entitled : Improved Long-Term Survival of Patients with Recurrent Medulloblastoma Treated with a “MEMMAT-like” Metronomic Antiangiogenic Approach .

the full text is available here

ABSTRACT

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.