Treatment outcomes in conventional high-grade osteosarcoma in children and adolescents: An analysis of survival of a cohort treated without methotrexate
DOI:
https://doi.org/10.35509/01239015.197Keywords:
Osteosarcoma, Chemotherapy, Survival, ColombiaAbstract
Objective: To report event-free overall survival rates and histological response results for neoadjuvant chemotherapy and limb-salvage surgery in conventional osteosarcoma patients treated without high methotrexate doses in the National Cancer Institute of Colombia.
Patients and Methods: A cohort of under 21-year old patients diagnosed with conventional osteosarcoma, with or without metastasis, underwent preoperative chemotherapy for twelve weeks, followed by local control surgery in week 15, and three postoperative chemotherapy cycles. Treatment did not include methotrexate. Four drugs were administered: ifosfamide, doxorubicin, cisplatin, and etoposide. The Kaplan-Meier method was used to calculate overall survival and event-free rates. A multivariate analysis of survival predictors was carried out with the Cox proportional hazards method. Statistical analysis was based on an α of 0.05.
Results: From January 1997 to December 2007, a total of l22 conventional osteosarcoma patients received treatment, with a median follow-up of 24.4 months (range 1.13 to 169).
The mean patient age was 13.7 years (SD±2.9 yrs). Limb-salvage surgery was performed in 52% and ablative surgery in 38%. Overall survival and event-free rates were higher in the good responders to chemotherapy than in the poor responders: (HR = 4.33; 95% CI; 1.77-10.58) and
(HR = 2.90; 95% CI; 1.60-5.27. The overall survival and event-free rates were different between patients with and without metastasis at diagnosis: (HR = 2.13; 95% CI; 0.97-4.72) and (HR = 2.07; (95% CI; 1.10-3.90).
Conclusion: Osteosarcoma can be treated with chemotherapy without high methotrexate doses to achieve moderately effective survival rates comparable with those in developed countries
Author Biographies
Amaranto Suárez, Instituto Nacional de Cancerología
Clínica de Oncología Pediátrica, Instituto Nacional de Cancerología, Bogotá D. C., Colombia
Camilo Soto, Instituto Nacional de Cancerología
Clínica de Ortopedia Oncológica, Instituto Nacional de Cancerología, Bogotá D. C., Colombia
Luis Gómez, Instituto Nacional de Cancerología
Clínica de Ortopedia Oncológica, Instituto Nacional de Cancerología, Bogotá D. C., Colombia
Óscar Gamboa, Instituto Nacional de Cancerología
Subdirección de investigación, vigilancia epidemiológica, promoción y prevención, Instituto Nacional de Cancerología, Bogotá D. C., Colombia
Diego Soto, Instituto Nacional de Cancerología
Clínica de Ortopedia Oncológica, Instituto Nacional de Cancerología, Bogotá D. C., Colombia
Santiago Escandón, Instituto Nacional de Cancerología
Clínica de Ortopedia Oncológica, Instituto Nacional de Cancerología, Bogotá D. C., Colombia
Greti Terselich, Instituto Nacional de Cancerología
Clínica de Oncología Pediátrica, Instituto Nacional de Cancerología, Bogotá D. C., Colombia
References
Scheurer ME, Bondy ML, Gurney JG. Epidemiology of childhood cancer. En: Pizzo PA, Poplack DC, editores. Principles and Practices of Pediatric Oncology. Sixth edition Philadelphia: Lippinccott Williams and Wilkins; 2011. p. 2-16.
Janeway KA, Gorlick R, Bernstein ML. Osteosarcoma. En: Orkin S, Fisher D, Look AT, Lux S, Ginsburg D, Nathan DG, editores. Oncology of infancy and childhood. Philadelphia: Saunders Elsevier; 2009. p. 871-910.
https://doi.org/10.1016/B978-1-4160-3431-5.00022-4
Bravo LE, Collazos T, García LS, Gutiérrez A, Carrascal EJ. (eds). Cáncer Infantil en Cali, Colombia, 1994-2003. Registro Poblacional de Cáncer de Cali, 2009.
Gorlick R, Bielack S, Teot L, Meyer J, Randall RL, Osteosarcoma. Biology, diagnosis, treatment and remaining challenges. En: Pizzo PA, Poplack DC, editores. Principles and Practices of Pediatric Oncology. Sixth edition Philadelphia: Lippinccott Williams and Wilkins; 2011. p. 1015-44.
Heare T, Hensley MA, Dell'Orfano S. Bone tumors: osteosarcoma and Ewing's sarcoma. Current Opinion in Pediatrics. 2009;21:365-72.
https://doi.org/10.1097/MOP.0b013e32832b1111
Rosen G, Tan C, Sanmaneechai A, Beattie EJ Jr, Marcove JR, Murphy ML. The rationale for multiple drug chemotherapy in the treatment of osteogenic sarcoma. Cancer. 1975;35 3 suppl:936-45.
https://doi.org/10.1002/1097-0142(197503)35:3+<936::AID-CNCR2820350714>3.0.CO;2-B
Jaffe N, Frei E 3rd, Traggis D, Watts H. Weekly high-dose methotrexate-citrovorum factor in osteogenic sarcoma: presurgical treatment of primary tumor and of overt pulmonary metastases. Cancer. 1977;39:45-50.
https://doi.org/10.1002/1097-0142(197701)39:1<45::AID-CNCR2820390109>3.0.CO;2-T
Rosen G, Suwansirikui S, Kwon C, Tan C, Wu SJ, Beattie EJ Jr, et al. High-dose methotrexate and citrovorum factor rescue and Adriamycin in childhood osteogenic sarcoma. Cancer. 1974;33:1151-63.
https://doi.org/10.1002/1097-0142(197404)33:4<1151::AID-CNCR2820330439>3.0.CO;2-8
Delepine N, Delepine G, Bacci G, Rosen G, Desbois J-C. Influence of methotrexate dose intensity on outcome of patients with high grade osteogenic osteosarcoma: Analysis of the literature. Cancer. 1996;78:2127-35.
https://doi.org/10.1002/(SICI)1097-0142(19961115)78:10<2127::AID-CNCR13>3.0.CO;2-0
Daw NC, Neel MD, Rao BN, Billups CA, Wu J, Jenkins JJ, et al. Frontline Treatment of Localized Osteosarcoma Without Methotrexate: Results of the St. Jude Children's Research Hospital OS99 Trial. Cancer. 2011;117:2770-8.
https://doi.org/10.1002/cncr.25715
Rosen G, Caparros B, Huvos AG, Kosloff C, Nirenberg A, Cacavio A, et al. Preoperative chemotherapy for osteogenic sarcoma: selection of postoperative adjuvant chemotherapy based on the response of the primary tumor to preoperative chemotherapy. Cancer. 1982;49:1221-30.
https://doi.org/10.1002/1097-0142(19820315)49:6<1221::AID-CNCR2820490625>3.0.CO;2-E
Meyer WH, Pratt CHB, Poquette CA, Rao BN, Parham DM, Marina NM, et al. Carboplatin/ifosfamide window therapy for osteosarcoma: results of the St Jude Children's Research Hospital OS-91 trial. J Clin Oncol. 2001;19:171-82.
https://doi.org/10.1200/JCO.2001.19.1.171
Meyers PA, Schwartz CL, Krailo M, Kleinerman ES, Betcher D, Bernstein ML, et al. Osteosarcoma: A randomized, prospective trial of the addition of ifosfamide and/or muramyl tripeptide to cisplatin, doxorubicin, and high-dose methotrexate. J Clin Oncol. 2005;23:2004-11.
https://doi.org/10.1200/JCO.2005.06.031
Crews KR, Liu T, Rodriguez-Galindo C, Tan M, Meyer WH, Panetta JC, et al. High-dose methotrexate pharmacokinetics and outcome of children and young adults with osteosarcoma. Cancer. 2004;100:1724-33.
https://doi.org/10.1002/cncr.20152
Epelman S, Seibel N, Melaragno R, et al. Treatment of newly diagnosed high grade osteosarcoma (OS) with ifosfamida (IFOS), adriamycin (ADR) and cisplatin (CDP) without high dose methotrexate [abstract]. Med Pediatr Oncol. 1996;27:226. Abstract O-61.
Stoller RG, Hande KR, Jacobs SA, Rosenberg SA, Chabner BA. Use of plasma pharmacokinetics to predict and preventmet hotrexate toxicity. N Engl J Med. 1977;297:630-4.
https://doi.org/10.1056/NEJM197709222971203
Estève MA, Devictor-Pierre B, Galy G, André N, Coze C, Lacarelle B, et al. Severe acute toxicity associated with high-dose methotrexate (MTX) therapy: use of therapeutic drug monitoring and test-dose to guide carboxypeptidase G2 rescue and MTX continuation. Eur J Clin Pharmacol. 2007;63:39-42.
https://doi.org/10.1007/s00228-006-0212-1
Whelan JS, Jinks RC, McTiernan A, Sydes MR, Hook JM, Trani L, et al. Survival from high-grade localised extremity osteosarcoma: combined results and prognostic factors from three European Osteosarcoma Intergroup randomised controlled trials. Ann Oncol. 2012;23:1607-16.
https://doi.org/10.1093/annonc/mdr491
The First Study of the European Osteosarcoma Intergroup Bramwell VH, Burgers M, Sneath R, Souhami R, Van Oosterom AT, Voúte PA, et al. A Comparison of Two Short Intensive Adjuvant Chemotherapy Regimens in Operable Osteosarcoma of Limbs in Children and Young Adults. J Clin Oncol. 1992;10:1579-91.
https://doi.org/10.1200/JCO.1992.10.10.1579
Tunn PU, Reichardt P. Chemotherapyfor osteosarcoma without high-dose methotrexate: a 12 year follow-up on 53 patients. Onkologie. 2007;30:228-32.
https://doi.org/10.1159/000100776
Eleutério SJ, Senerchia AA, Almeida MT, Da Costa CM, Lustosa D, Calheiros LM, et al. Osteosarcoma in patients younger than 12 years old sithout metastases have similar prognosis as adolescent and young adults. Pediatr Blood Cancer. 2015;62:1209-13.
https://doi.org/10.1002/pbc.25459
Petrilli AS, Brunetto AL, Cypriano Mdos S, Ferraro AA, Donato Macedo CR, Senerchia AA, et al. Fifteen Years' Experience of the Brazilian Osteosarcoma Treatment Group (BOTG): A Contribution from an Emerging Country. J Adolesc Young Adult Oncol. 2013;2:145-52.
https://doi.org/10.1089/jayao.2013.0012
Xu M, Xu SF, Yu XC. Clinical analysis of osteosarcoma patients treated with high-dose methotrexate-free neoadjuvant chemotherapy. Curr Oncol. 2014;21:e678-84.
https://doi.org/10.3747/co.21.1973
Bacci G, Longhi A, Fagioli F, Briccoli A, Versari M, Picci P. Adjuvant and neoadjuvant chemotherapy for osteosarcoma of the extremities: 27 year experience at Rizzoli Institute, Italy. Eur J. Cancer. 2005;41:2836-45.
https://doi.org/10.1016/j.ejca.2005.08.026
Goorin AM, Perez-Atayde A, Gebhardt M, Andersen JW, Wilkinson RH, Delorey MJ, et al. Weekly highdose methotrexate and doxorubicin for osteosarcoma; the Dana Farber Cancer Institute/the Childrens Hospital-study III. J Clin Oncol. 1987;5:1178-84.
https://doi.org/10.1200/JCO.1987.5.8.1178
Provisor AJ, Ettinger LJ, Nachman JB, Krailo MD, Makley JT, Yunis EJ, et al. Treatment of nonmetastatic osteosarcoma of the extremity with pre-operative and postoperative chemotherapy: a report from the Children's. Cancer. Group. J Clin Oncol. 1997;15:76-84.
https://doi.org/10.1200/JCO.1997.15.1.76
Bacci G, Ferrari S, Mercuri M, Bertoni F, Picci P, Manfrini M, et al. Predictive factors for local recurrence in osteosarcoma: 540 patients with extremety tumors followed for minimum 2.5 years after neoadjuvant chemotherapy. Acta Orthop Scand. 1998;69:230-6.
https://doi.org/10.3109/17453679809000921
Smeland S, Müller C, Alvegard TA, Wiklund T, Wiebe T, Björk O, et al. Scandinavian Sarcoma Group Osteosarcoma Study SSG VIII: prognostic factors for outcome and the role of replacement salvage chemotherapy for poor histological responders. Eur J Cancer. 2003;39:488-94.
https://doi.org/10.1016/S0959-8049(02)00747-5
Southwest Oncology Group study 9139Zalupski MM, Rankin C, Ryan JR, Lucas DR, Muler J, Lanier KS, et al. Adjuvant therapy of osteosarcoma-A Phase II trial. Cancer. 2004;100:818-25.
How to Cite
Downloads
Downloads
Published
Issue
Section
License
Todos los derechos reservados.
