Results of a Randomized, Prospective Clinical Trial Evaluating Metronomic Chemotherapy in Nonmetastatic Patients With High-Grade, Operable Osteosarcomas of the Extremities: A Report From the Latin American Group of Osteosarcoma Treatment

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art_SENERCHIA_Results_of_a_Randomized_Prospective_Clinical_Trial_Evaluating_2017.PDF (329.48 KB)
Citações na Scopus
42
Tipo de produção
article
Data de publicação
2017
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
WILEY
Autores
SENERCHIA, Andreza A.
MACEDO, Carla Renata
FERMAN, Sima
SCOPINARO, Marcelo
CACCIAVILLANO, Walter
BOLDRINI, Erica
MORAES, Vera Lucia Lins de
REY, Guadalupe
OLIVEIRA, Claudia T. de
CASTILLO, Luis
Citação
CANCER, v.123, n.6, p.1003-1010, 2017
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
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. (C) 2016 American Cancer Society.
Palavras-chave
chemotherapy, metronomic, nonmetastatic, osteosarcoma, survival
URI
https://observatorio.fm.usp.br/handle/OPI/20281
Referências
  1. Andre N, 2015, ONCOTARGET, V6, P23008, DOI 10.18632/oncotarget.3984
  2. Andre N, 2014, NAT REV CLIN ONCOL, V11, P413, DOI 10.1038/nrclinonc.2014.89
  3. Andre N, 2011, ONCOTARGET, V2, P960
  4. Barillet M, 2015, BRIT J CLIN PHARMACO, V80, P1289, DOI 10.1111/bcp.12734
  5. Bertolini F, 2003, CANCER RES, V63, P4342
  6. Bhatia S, 2015, JAMA ONCOL, V1, P287, DOI 10.1001/jamaoncol.2015.0245
  7. Bielack SS, 2015, J CLIN ONCOL, V33, P2279, DOI 10.1200/JCO.2014.60.0734
  8. Colleoni M, 2002, ANN ONCOL, V13, P73, DOI 10.1093/annonc/mdf013
  9. Connell AM, 2009, AM J DRUG ALCOHOL AB, V35, P253, DOI 10.1080/00952990903005882
  10. Ebos JML, 2014, EMBO MOL MED, V6, P1561, DOI 10.15252/emmm.201403989
  11. Felgenhauer JL, 2013, PEDIATR BLOOD CANCER, V60, P409, DOI 10.1002/pbc.24328
  12. Gravel J, 2007, CLIN TRIALS, V4, P350, DOI 10.1177/1740774507081223
  13. HUVOS AG, 1977, ARCH PATHOL LAB MED, V101, P14
  14. Jo B, 2002, PSYCHOL METHODS, V7, P178, DOI 10.1037//1082-989X.7.2.178
  15. Kreuter M, 2004, CLIN CANCER RES, V10, P8531, DOI 10.1158/1078-0432.CCR-04-0969
  16. Luetke A, 2014, CANCER TREAT REV, V40, P523, DOI 10.1016/j.ctrv.2013.11.006
  17. Malik Prabhat Singh, 2014, Front Oncol, V4, P76, DOI 10.3389/fonc.2014.00076
  18. Marina N, 2009, CANCER TREAT RES, V152, P339, DOI 10.1007/978-1-4419-0284-9_18
  19. Mathes T, 2014, CANCER EPIDEMIOL, V38, P214, DOI 10.1016/j.canep.2014.03.012
  20. Meyers PA, 2008, J CLIN ONCOL, V26, P633, DOI 10.1200/JCO.2008.14.0095
  21. Minard-Colin V, 2012, EUR J CANCER, V48, P2409, DOI 10.1016/j.ejca.2012.04.012
  22. Minturn JE, 2011, PEDIATR BLOOD CANCER, V56, P39, DOI 10.1002/pbc.22690
  23. Mirabello L, 2009, CANCER, V115, P1531, DOI 10.1002/cncr.24121
  24. Pasquier E, 2010, NAT REV CLIN ONCOL, V7, P455, DOI 10.1038/nrclinonc.2010.82
  25. Petrilli AS, 1999, MED PEDIATR ONCOL, V33, P71, DOI 10.1002/(SICI)1096-911X(199908)33:2<71::AID-MPO2>3.0.CO;2-T
  26. Petrilli AS, 2006, J CLIN ONCOL, V24, P1161, DOI 10.1200/JCO.2005.03.5352
  27. PETRILLI AS, 1991, CANCER, V68, P733, DOI 10.1002/1097-0142(19910815)68:4<733::AID-CNCR2820680412>3.0.CO;2-0
  28. PETRILLI S, 1991, CLIN ORTHOP RELAT R, P60
  29. Peyrl A, 2012, PEDIATR BLOOD CANCER, V59, P511, DOI 10.1002/pbc.24006
  30. Rubin G, 1998, CHILD NERV SYST, V14, P167, DOI 10.1007/s003810050205
  31. Russell HV, 2011, PEDIATR BLOOD CANCER, V57, P275, DOI 10.1002/pbc.22821
  32. Simkens LHJ, 2015, LANCET, V385, P1843, DOI 10.1016/S0140-6736(14)62004-3
  33. Stempak D, 2006, CANCER INVEST, V24, P432, DOI 10.1080/07357900600705599
  34. Traore F, 2013, INDIAN J CANCER, V50, P250, DOI 10.4103/0019-509X.118741
  35. Whelan JS, 2015, ANN ONCOL, V26, P407, DOI 10.1093/annonc/mdu526

Coleções
Artigos e Materiais de Revistas Científicas - HC/ICr
Artigos e Materiais de Revistas Científicas - ODS/03