Carboplatin in the treatment of Ewing sarcoma: Results of the first Brazilian collaborative study group for Ewing sarcoma family tumors-EWING1.
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.


METHODS
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).


CONCLUSIONS
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.
Children's Cancer Institute, Porto Alegre, RS, Brazil.
Algemir L
AL
Brunetto
Hospital Pereira Rossell, Montevideo, Uruguay.
Luis A
LA
Castillo
Department of Pediatrics, Pediatric Oncology Institute (IOP/GRAACC/UNIFESP), Federal University of S, ã, o Paulo, São Paulo, SP, Brazil.
Antonio S
AS
Petrilli
Department of Pediatrics, Pediatric Oncology Institute (IOP/GRAACC/UNIFESP), Federal University of S, ã, o Paulo, São Paulo, SP, Brazil.
Carla D
CD
Macedo
Fundação Pio XII - Hospital Infantojuvenil, Barretos, SP, Brazil.
Erica
E
Boldrini
Hospital do Câncer AC Camargo, São Paulo, SP, Brazil.
Cecilia
C
Costa
Hospital das Clínicas de São Paulo - ITACI, São Paulo, SP, Brazil.
Maria T
MT
Almeida
Hospital da Criança Santo Antonio, Porto Alegre, RS, Brazil.
Daniela
D
Kirst
Dana-Farber Cancer Institute, Boston, Maryland.
Carlos
C
Rodriguez-Galindo
Hospital Universit, á, rio de Santa Maria, Santa Maria, RS, Brazil.
Waldir V
WV
Pereira
Hospital Infantil Pequeno Príncipe, Curitiba, PR, Brazil.
Flora M
FM
Watanabe
Santa Casa de Misericórdia de São Paulo, SP, Brazil.
Maria
M
Pizza
Instituto de Clínicas Pediátricas Bolívar Risso, Jundiaí, SP, Brazil.
Eliana
E
Benites
Hospital Universitário Oswaldo Cruz, Recife, PE, Brazil.
Vera
V
Morais
Hospital Napoleão Laureano, João Pessoa, PB, Brazil.
Andréa
A
Gadelha
Instituto de Pediatria, UFRJ, Rio de Janeiro, RJ, Brazil.
Antônio
A
Nakasato
Children's Cancer Institute, Porto Alegre, RS, Brazil.
Ana L
AL
Abujamra
Hospital São Lucas - PUC-RS, Porto Alegre, RS, Brazil.|Hospital de Clínicas de Porto Alegre, Department of Pediatrics, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
Lauro J
LJ
Gregianin
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000401:mortality; D001938:Brazil; D016190:Carboplatin / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D060828:Induction Chemotherapy / Q000379:methods; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D008297:Male; D016016:Proportional Hazards Models; D012512:Sarcoma, Ewing / Q000188:drug therapy* / Q000401:mortality; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000401:mortality; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D016190:Carboplatin; D007069:Ifosfamide
Ewing/PNET; VDC/ICE; metastatic disease