Andreza A Senerchia1, Carla Renata Macedo1, Sima Ferman2, Marcelo Scopinaro3, Walter Cacciavillano3, Erica Boldrini4, Vera Lúcia Lins de Moraes5, Guadalupe Rey6, Claudia T de Oliveira7, Luis Castillo8, Maria Tereza Almeida9, Maria Luisa Borsato10, Eduardo Lima11, Daniel Lustosa12, José Henrique Barreto13, Tatiana El-Jaick14, Simone Aguiar15, Algemir Brunetto16, Lauro Greggiani17, Hugo Cogo-Moreira18, Alvaro Atallah18, Antonio Sergio Petrilli1. 1. Institute of Pediatric Oncology/Support Group for Adolescents and Children With Cancer, Federal University of Sao Paulo, Sao Paulo, Brazil. 2. National Cancer Institute, Rio de Janeiro, Brazil. 3. Hospital de Pediatria SAMIC-Professor Dr. Juan P. Garrahan, Buenos Aires, Argentina. 4. Barretos Cancer Hospital, Barretos, Brazil. 5. Oswaldo Cruz Hospital, Oncohematology Pediatric Center, Recife, Brazil. 6. R. Gutierrez Children's Hospital, Buenos Aires, Argentina. 7. Amaral Carvalho Hospital, Jau, Brazil. 8. Pereira Rossell Hospital, Montevideo, Uruguay. 9. Clinical Hospital, Children's Institute, Sao Paulo, Brazil. 10. Santa Casa de Misericordia de Sao Paulo, Sao Paulo, Brazil. 11. Baleia Hospital, Sao Paulo, Brazil. 12. Hospital do Cancer do Ceara, Fortaleza, Brazil. 13. Cancer Clinic, Bahia Society of Oncology, Salvador, Brazil. 14. Joana de Gusmão Children's Hospital, Santa Catarina, Brazil. 15. Centro Infantil Boldrini, San Paulo, Brazil. 16. Childhood Cancer Institute, Porto Alegre, Brazil. 17. Sao Lucas Hospital, Porto Alegre, Brazil. 18. Federal University of Sao Paulo, Sao Paulo, Brazil.
Abstract
BACKGROUND: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-grade operable osteosarcomas (OSTs) of the extremities was investigated. METHODS:Patients with high-grade 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-free survival (EFS) from randomization. RESULTS: 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 toMAP plus MC (n = 139) or MAP alone (n = 157). At 5 years, the EFS cumulative proportions surviving in the MAP-MC group and the MAP-alone 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; P =.395). The multivariate analysis showed that necrosis grades 1 and 2, tumor size, and amputation were associated with shorter EFS. CONCLUSIONS: According to the current follow-up, EFS with MAP plus MC is not statistically superior to EFS with MAP alone in patients with high-grade, resectable OSTs of the extremities. Cancer 2017;123:1003-10.
RCT Entities:
BACKGROUND: 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-grade operable osteosarcomas (OSTs) of the extremities was investigated. METHODS:Patients with high-grade 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-free survival (EFS) from randomization. RESULTS: 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-MC group and the MAP-alone 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; P =.395). The multivariate analysis showed that necrosis grades 1 and 2, tumor size, and amputation were associated with shorter EFS. CONCLUSIONS: According to the current follow-up, EFS with MAP plus MC is not statistically superior to EFS with MAP alone in patients with high-grade, resectable OSTs of the extremities. Cancer 2017;123:1003-10.
Authors: Marina Curra; Amanda F Gabriel; Maria Beatriz C Ferreira; Marco Antonio T Martins; André T Brunetto; Lauro J Gregianin; Manoela Domingues Martins Journal: Support Care Cancer Date: 2021-04-12 Impact factor: 3.603
Authors: Daniel Heudobler; Michael Rechenmacher; Florian Lüke; Martin Vogelhuber; Tobias Pukrop; Wolfgang Herr; Lina Ghibelli; Christopher Gerner; Albrecht Reichle Journal: Int J Mol Sci Date: 2018-11-09 Impact factor: 5.923