Lowered Cisplatin Dose and No Bleomycin in the Treatment of Pediatric Germ Cell Tumors: Results of the GCT-99 Protocol From the Brazilian Germ Cell Pediatric Oncology Cooperative Group

J Clin Oncol. 2016 Feb 20;34(6):603-10. doi: 10.1200/JCO.2014.59.1420. Epub 2016 Jan 4.

Abstract

Purpose: We describe the results of a risk-adapted, response-based therapeutic approach from the Brazilian GCT-99 study on germ cell tumors.

Patients and methods: From May 1999 to October 2009, 579 participants were enrolled in the Brazilian GCT-99 study. Treatment, defined as specific chemotherapy regimen and number of cycles, was allocated by means of risk-group assignment at diagnosis with consideration for stage and primary tumor site. Patients at low risk received no chemotherapy. Patients at intermediate risk (IR) with a good response (GR) received four cycles of platinum and etoposide (PE), for total doses of platinum 420 mg/m(2) and etoposide 2,040 mg/m(2). Patients at IR with a partial response (PR) received three cycles of PE plus three cycles of ifosfamide, vinblastine, and bleomycin. Patients at high risk (HR) with a GR received four cycles of PE and ifosfamide (PEI) at total doses of platinum 420 mg/m(2), etoposide 1,200 mg/m(2), and ifosfamide 30 g/m(2). Patients at HR with a PR received six cycles of PEI.

Results: The risk-group distribution was 213 LR, 138 IR, and 129 HR for 480 evaluable patients. Overall survival (OS) and event-free survival (EFS) rates at 10 years were, respectively, 90% and 88.6% in the IR-GR group (n = 126) and 74.1% and 74.1% in the IR-PR group (n = 12). Ten-year rates for the HR-GR group (n = 86) were an OS of 66.8% and an EFS of 62.5%. The HR-PR group (n = 43) had an OS of 74.8% and an EFS of 73.4%. In univariable and multivariable analysis, increased serum lactate dehydrogenase level and histology for a metastatic immature teratoma were prognostic of a worsened outcome.

Conclusion: Reduction of therapy to two drugs did not compromise survival outcomes for patients in the IR-GR group, and escalation of therapy with PEI did not significantly improve OS and EFS in patients at HR.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Bleomycin*
  • Brazil
  • Child
  • Cisplatin / administration & dosage*
  • Disease-Free Survival
  • Etoposide / administration & dosage
  • Female
  • Head and Neck Neoplasms / drug therapy*
  • Humans
  • Ifosfamide / administration & dosage
  • Male
  • Mediastinal Neoplasms / drug therapy*
  • Neoplasms, Germ Cell and Embryonal / drug therapy*
  • Neoplasms, Germ Cell and Embryonal / pathology
  • Ovarian Neoplasms / drug therapy*
  • Retroperitoneal Neoplasms / drug therapy*
  • Risk Assessment
  • Survival Rate
  • Testicular Neoplasms / drug therapy*
  • Vaginal Neoplasms / drug therapy*
  • Vinblastine / administration & dosage

Substances

  • Bleomycin
  • Vinblastine
  • Etoposide
  • Cisplatin
  • Ifosfamide