{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T10:40:27Z","timestamp":1785235227882,"version":"3.55.0"},"reference-count":35,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2016,11,7]],"date-time":"2016-11-07T00:00:00Z","timestamp":1478476800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2017,3,15]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Metronomic chemotherapy (MC) consists of the administration of a low dose of chemotherapy on a daily or weekly basis without a long break to achieve an antitumoral effect through an antiangiogenic effect or stimulation of the immune system. The potential effect of MC with continuous oral cyclophosphamide and methotrexate in patients with high\u2010grade operable osteosarcomas (OSTs) of the extremities was investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Patients with high\u2010grade OSTs who were 30 years old or younger were eligible for registration at diagnosis. Eligibility for randomization included 1) nonmetastatic disease and 2) complete resection of the primary tumor. The study design included a backbone of 10 weeks of preoperative therapy with methotrexate, adriamycin, and platinum (MAP). After surgery, patients were randomized between 2 arms to complete 31 weeks of MAP or receive 73 weeks of MC after MAP. The primary endpoint was event\u2010free survival (EFS) from randomization.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>There were 422 nonmetastatic patients registered (May 2006 to July 2013) from 27 sites in 3 countries (Brazil, Argentina and Uruguay), and 296 were randomized to MAP plus MC (n = 139) or MAP alone (n = 157). At 5 years, the EFS cumulative proportions surviving in the MAP\u2010MC group and the MAP\u2010alone group were 61% (standard error [SE], 0.5%) and 64% (SE, 0.5%), respectively, and they were not statistically different (Wilcoxon [Gehan] statistic = 0.724; <jats:italic>P<\/jats:italic> =.395). The multivariate analysis showed that necrosis grades 1 and 2, tumor size, and amputation were associated with shorter EFS.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>According to the current follow\u2010up, EFS with MAP plus MC is not statistically superior to EFS with MAP alone in patients with high\u2010grade, resectable OSTs of the extremities. <jats:bold><jats:italic>Cancer<\/jats:italic> 2017;123:1003\u201310.<\/jats:bold> \u00a9 <jats:italic>2016 American Cancer Society<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.30411","type":"journal-article","created":{"date-parts":[[2016,11,7]],"date-time":"2016-11-07T12:32:04Z","timestamp":1478521924000},"page":"1003-1010","source":"Crossref","is-referenced-by-count":46,"title":["Results of a randomized, prospective clinical trial evaluating metronomic chemotherapy in nonmetastatic patients with high\u2010grade, operable osteosarcomas of the extremities: A report from the Latin <scp>A<\/scp>merican Group of Osteosarcoma Treatment"],"prefix":"10.1002","volume":"123","author":[{"given":"Andreza A.","family":"Senerchia","sequence":"first","affiliation":[{"name":"Institute of Pediatric Oncology\/Support Group for Adolescents and Children With Cancer Federal University of Sao Paulo Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla Renata","family":"Macedo","sequence":"additional","affiliation":[{"name":"Institute of Pediatric Oncology\/Support Group for Adolescents and Children With Cancer Federal University of Sao Paulo Sao Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sima","family":"Ferman","sequence":"additional","affiliation":[{"name":"National Cancer Institute Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo","family":"Scopinaro","sequence":"additional","affiliation":[{"name":"Hospital de Pediatria SAMIC\u2013Professor Dr. Juan P. 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