Algemir L Brunetto1, Luis A Castillo2, Antonio S Petrilli3, Carla D Macedo3, Erica Boldrini4, Cecilia Costa5, Maria T Almeida6, Daniela Kirst7, Carlos Rodriguez-Galindo8, Waldir V Pereira9, Flora M Watanabe10, Maria Pizza11, Eliana Benites12, Vera Morais13, Andréa Gadelha14, Antônio Nakasato15, Ana L Abujamra1, Lauro J Gregianin16,17. 1. Children's Cancer Institute, Porto Alegre, RS, Brazil. 2. Hospital Pereira Rossell, Montevideo, Uruguay. 3. Department of Pediatrics, Pediatric Oncology Institute (IOP/GRAACC/UNIFESP), Federal University of S, ã, o Paulo, São Paulo, SP, Brazil. 4. Fundação Pio XII - Hospital Infantojuvenil, Barretos, SP, Brazil. 5. Hospital do Câncer AC Camargo, São Paulo, SP, Brazil. 6. Hospital das Clínicas de São Paulo - ITACI, São Paulo, SP, Brazil. 7. Hospital da Criança Santo Antonio, Porto Alegre, RS, Brazil. 8. Dana-Farber Cancer Institute, Boston, Maryland. 9. Hospital Universit, á, rio de Santa Maria, Santa Maria, RS, Brazil. 10. Hospital Infantil Pequeno Príncipe, Curitiba, PR, Brazil. 11. Santa Casa de Misericórdia de São Paulo, SP, Brazil. 12. Instituto de Clínicas Pediátricas Bolívar Risso, Jundiaí, SP, Brazil. 13. Hospital Universitário Oswaldo Cruz, Recife, PE, Brazil. 14. Hospital Napoleão Laureano, João Pessoa, PB, Brazil. 15. Instituto de Pediatria, UFRJ, Rio de Janeiro, RJ, Brazil. 16. Hospital São Lucas - PUC-RS, Porto Alegre, RS, Brazil. 17. Hospital de Clínicas de Porto Alegre, Department of Pediatrics, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
Abstract
BACKGROUND: Large cooperative group studies have shown the efficacy of risk-adapted treatment for Ewing sarcoma. However, validation and local adaptation by National cooperative groups is needed. A multicenter protocol to determine the efficacy and safety of a risk-adapted intensive regimen was developed by the Brazilian cooperative group. PROCEDURE: Patients <30 years old with Ewing sarcoma were eligible. Induction chemotherapy consisted of two cycles of ICE (ifosfamide, carboplatin, and etoposide) followed by two cycles of VDC (vincristine, doxorubicin, and cyclophosphamide), followed by local control. Patients with low risk (LR) disease (localized resectable with normal LDH) received 10 additional alternating courses of IE with VDC. For patients with high-risk (HR) disease (unresectable, pelvic, metastatic, or high LDH), two additional cycles of ICE were given. RESULTS: One-hundred seventy five patients (39% metastatic) were enrolled. Fifty-two patients (29.7%) were LR and 123 (70.3%) were HR. Overall response rate at end of induction was 27.4%. Five-year event-free survival (EFS) and overall survival (OS) estimates were 51.4% and 54.4%, respectively. Patients with localized disease had better outcomes than patients with metastases (5-year EFS 67.9% vs. 25.5%, and 5-year OS 70.3% vs. 29.1%, respectively). On multivariate analysis, the presence of metastatic disease was the only prognostic factor (P < 0.01). CONCLUSION: The VDC/ICE protocol was feasible, and considering the high tumor burden in our population, resulted in comparable results to those reported by cooperative groups in high-income countries. Further adaptation to maximize efficacy and minimize toxicity will be required.
BACKGROUND: Large cooperative group studies have shown the efficacy of risk-adapted treatment for Ewing sarcoma. However, validation and local adaptation by National cooperative groups is needed. A multicenter protocol to determine the efficacy and safety of a risk-adapted intensive regimen was developed by the Brazilian cooperative group. PROCEDURE: Patients <30 years old with Ewing sarcoma were eligible. Induction chemotherapy consisted of two cycles of ICE (ifosfamide, carboplatin, and etoposide) followed by two cycles of VDC (vincristine, doxorubicin, and cyclophosphamide), followed by local control. Patients with low risk (LR) disease (localized resectable with normal LDH) received 10 additional alternating courses of IE with VDC. For patients with high-risk (HR) disease (unresectable, pelvic, metastatic, or high LDH), two additional cycles of ICE were given. RESULTS: One-hundred seventy five patients (39% metastatic) were enrolled. Fifty-two patients (29.7%) were LR and 123 (70.3%) were HR. Overall response rate at end of induction was 27.4%. Five-year event-free survival (EFS) and overall survival (OS) estimates were 51.4% and 54.4%, respectively. Patients with localized disease had better outcomes than patients with metastases (5-year EFS 67.9% vs. 25.5%, and 5-year OS 70.3% vs. 29.1%, respectively). On multivariate analysis, the presence of metastatic disease was the only prognostic factor (P < 0.01). CONCLUSION: The VDC/ICE protocol was feasible, and considering the high tumor burden in our population, resulted in comparable results to those reported by cooperative groups in high-income countries. Further adaptation to maximize efficacy and minimize toxicity will be required.
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