Cisplatin and Etoposide in Childhood Germ Cell Tumor: Brazilian Pediatric Oncology Society Protocol GCT-91 Luiz Fernando Lopes, Carla Renata Pacheco Macedo, Elita ˆnia Marinho Pontes, Simone dos Santos Aguiar, Maria Jose ´ Mastellaro, Renato Melaragno, Sonia Maria Rossi Vianna, Paula Azevedo Allemand Lopes, Nubia Mendonc ¸a, Maria Teresa de Assis Almeida, Viviane Sonaglio, Karina B. Ribeiro, Victor M. Santana, Dominik T. Schneider, and Beatriz de Camargo From the Brazilian Germ Cell Tumour Study Group of the Sociedade Brasileira de Oncologia Pediátrica, Centro de Tratamento e Pesquisa Hospital do Ca ˆ ncer; Instituto de Oncologia Pediat- rica, Universidade Federal de Sa ˜o Paulo; Hospital Santa Marcelina; Hospi- tal do Servidor Publico Estadual; and Instituto da Crianc ¸ a, Universidade de Sa ˜o Paulo, Sa ˜ o Paulo; Grupo de Pedia- tria Oncologica, Sa ˜ o Jose dos Campos; Centro Infantil Boldrini, Campinas; Hospital de Base do Distrito Federal, Brasilia; and Clinica Onco, Salvador, Brazil; Departement of Oncology, St Jude Children’s Research Hospital, Memphis, TN; and Clinic of Pediatrics, Dortmund, Germany. Submitted January 26, 2008; accepted September 30, 2008; published online ahead of print at www.jco.org on January 21, 2009. Authors’ disclosures of potential con- flicts of interest and author contribu- tions are found at the end of this article. Corresponding author: Luiz Fernando Lopes, MD, PhD, Sociedade Brasileira de Oncologia Pedia ´ trica, Av Moema, 94 cj 31, Cep 04077-020 Sa ˜ o Paulo-SP, Brasil; e-mail: lf.lopes@yahoo.com. © 2009 by American Society of Clinical Oncology 0732-183X/09/2708-1297/$20.00 DOI: 10.1200/JCO.2008.16.4202 A B S T R A C T Purpose In 1988, we formed a consortium of Brazilian institutions to develop uniform standards for the diagnostic assessment and multidisciplinary treatment of children and adolescents with germ cell tumors. We also implemented the first childhood Brazilian germ cell tumor protocol, GCT-91, evaluating two-agent chemotherapy with cisplatin and etoposide (PE). We now report on the clinical characteristics and survival of children and adolescents with germ cell tumors treated on this protocol. Patients and Methods From May 1991 to April 2000, 115 patients (106 assessable patients) were enrolled onto the Brazilian protocol with a diagnosis of germ cell tumor. Results Patients were treated with surgery only (n = 35) and chemotherapy (n = 71). Important prognostic factors included stage (P = .025), surgical procedure at diagnosis according to resectability (P  .032), and abnormal lactate dehydrogenase value at diagnosis (P  .001). Conclusion The improvement in survival by the introduction of a standard protocol is an important achieve- ment. This is of particular importance for smaller institutions with previous limited experience in the treatment of childhood germ cell tumors. In addition, the results of a two-agent regimen with PE were favorable (5-year overall survival rate is 83.3% for patients in the high-risk group [n = 36] who received PE v 58.8% for patients in the high-risk patients group who received PE plus ifosfamide, vinblastine, and bleomycin [n = 17; P = .017]). Thus for selected patients, complex three-agent regimens may not be necessary to achieve long-term survival, even for some patients with advanced disease. J Clin Oncol 27:1297-1303. © 2009 by American Society of Clinical Oncology INTRODUCTION Malignant germ cell tumors (GCTs) are rare tu- mors, corresponding to approximately 3% of child- hood cancers. 1 GCTs may develop at many different midline sites and, especially during infancy and childhood, extragonadal tumors predominate. The vast majority of GCTs are extremely sensi- tive to chemotherapy, and cisplatin constitutes the most effective single agent in the treatment of GCTs. Other drugs such as etoposide, vinblastine, bleomy- cin, carboplatin, ifosfamide and, more recently, pac- litaxel also have proven activity. 2 On the basis of this experience, several multiagent regimens have been developed, which usually include cisplatin and eto- poside (PE) in combination with bleomycin or ifos- famide. These three-agent regimens are regarded as the current standard in the treatment of childhood GCTs. 3 However, the two-agent combination of PE was found to be effective in GCT in adults. 4,5 In addition, some data demonstrate that, particularly in infants and very young children, bleomycin may be associated with unacceptable toxicity. 6-8 The Brazilian Childhood Germ Cell Tumor Study Group was formed in 1988. The first aim of the study consortium was to develop uniform standards for diagnostic assessment and multidis- ciplinary treatment across the different institu- tions in Brazil that treat children and adolescents with GCTs. In addition, processes and infrastruc- tures for central documentation, consultation, and evaluation of Brazilian children with GCTs were established. In May 1991, we initiated the first Bra- zilian protocol (GCT-91) that evaluated a two-drug JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T VOLUME 27  NUMBER 8  MARCH 10 2009 © 2009 by American Society of Clinical Oncology 1297 Downloaded from jco.ascopubs.org on April 26, 2012. For personal use only. No other uses without permission. Copyright © 2009 American Society of Clinical Oncology. All rights reserved.