{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T21:01:29Z","timestamp":1787086889668,"version":"build-2736575974"},"reference-count":30,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,7,13]],"date-time":"2020-07-13T00:00:00Z","timestamp":1594598400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Lalla Salma Foundation Prevention and Treatment of Cancer"},{"name":"Cancer research Institute in Morocco"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>In low\u2010 and middle\u2010income countries, therapeutic options for advanced, refractory, or relapsing malignancies are limited due to local constraints such as cost of drugs, distance from oncology centers, and lack of availability of new anticancer drugs. Metronomics, which combines metronomic chemotherapy (MC) and drug repositioning, allows for the provision of new therapeutic options for patients in this setting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim of the study<\/jats:title><jats:p>To evaluate the activity and toxicity of a metronomic regimen in Moroccan pediatric patients with refractory or relapsing malignancies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and methods<\/jats:title><jats:p>From July 2014 to January 2018, patients with refractory\/relapsing solid tumors treated in five pediatric oncology centers were consecutively enrolled. The metronomic regimen consisted of 28\u2010day cycles with daily oral administration of cyclophosphamide (30\u00a0mg\/m<jats:sup>2<\/jats:sup>) from days 1 to 21, together with oral etoposide (25\u00a0mg\/m<jats:sup>2<\/jats:sup>) from days 1 to 21 followed by break of one week and daily valproic acid (20\u00a0mg\/kg) from days 1 to 28.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Ninety\u2010eight children (median age, 8 years) were included. Underlying malignancies were neuroblastoma (24 patients), Ewing sarcoma (18), osteosarcoma (14), rhabdomyosarcoma (14), and miscellaneous tumors (28). A total of 557 cycles were given (median: 6; range, 1\u201018 cycles). One\u2010year progression\u2010free survival of our patients was 19%, and one\u2010year overall survival was 22%. Complete response was obtained in three cases (3%), partial response in 11 cases (11%), and tumor stabilization for more than six months in 28 cases (28%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This three\u2010drug metronomic combination was well tolerated and associated with tumor response and disease stabilization in 42 patients even for a long period.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.28508","type":"journal-article","created":{"date-parts":[[2020,7,13]],"date-time":"2020-07-13T15:20:16Z","timestamp":1594653616000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Metro\u2010SMHOP 01: Metronomics combination with cyclophosphamide\u2010etoposide and valproic acid for refractory and relapsing pediatric malignancies"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9187-4149","authenticated-orcid":false,"given":"Maria","family":"El kababri","sequence":"first","affiliation":[{"name":"Paediatric Haematology and Oncology Center, Children's Hospital of Rabat Mohammed V University  Rabat Morocco"},{"name":"Metronomics Global Health Initiative  Rabat Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarra","family":"Benmiloud","sequence":"additional","affiliation":[{"name":"Paediatric Haematology and Oncology Unit Hospital Hassan II  Fes Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siham","family":"Cherkaoui","sequence":"additional","affiliation":[{"name":"Paediatric Haematology and Oncology Service Hospital 20 Aout  Casablanca Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamila","family":"El houdzi","sequence":"additional","affiliation":[{"name":"Pediatic Haematology and Oncology Unit Hospital Mohamed VI  Marrakech 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