Pilot study of cisplatin, etoposide, bleomycin, and escalating dose cyclophosphamide therapy for children with high risk germ cell tumors

A report of the children's oncology group (COG)

Marcio Malogolowkin, Mark Krailo, Neyssa Marina, Thomas Olson, A. Lindsay Frazier

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: To establish the maximum tolerated dose (MTD) and toxicity profile of cyclophosphamide with cisplatin, etoposide, and bleomycin (C-PEB) in children with high-risk malignant germ cell tumors (HR-MGCT). Procedure: Eligibility criteria included untreated patients≤21 years of age with stage III/IV extragonadal, extra cranial MGCT. Patients received four cycles (repeated every 3 weeks) of cisplatin (20mg/m2/day×5 days), etoposide (100mg/m2/day×5 days), and bleomycin (15mg/m2 on Day 1) with escalating doses of cyclophosphamide on Day 1, assigned at the time of enrollment (1.2, 1.8, or 2.4g/m2). Patients with complete response had therapy discontinued. Patients with residual disease underwent second-look surgery, those with pathologic evidence of residual MGCT or whose markers had not normalized received two more cycles. All other patients had protocol therapy stopped. Results: Nineteen patients were enrolled between July 2004 and August 2007. Three patients were non-evaluable. Sixteen patients completed four cycles. Eleven had complete response, one had progressive disease and four had partial response. All four with partial response underwent second look surgery followed by two more cycles. Only one patient, on dose 1.8g/m2, experienced dose-limiting toxicity (DLT) during the first cycle of therapy (grade 3 hyperglycemia). The 4-year EFS and OS (± standard deviation) were 74±7% and 89±10%, respectively. Conclusion: The addition of cyclophosphamide to the standard PEB regimen (cisplatin, etoposide, and bleomycin) is feasible and well-tolerated at all dose levels used on this study. Pediatr Blood Cancer 2013;60:1602-1605.

Original languageEnglish (US)
Pages (from-to)1602-1605
Number of pages4
JournalPediatric Blood and Cancer
Volume60
Issue number10
DOIs
StatePublished - Oct 1 2013
Externally publishedYes

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Germ Cell and Embryonal Neoplasms
Bleomycin
Etoposide
Cyclophosphamide
Cisplatin
Second-Look Surgery
Therapeutics
Maximum Tolerated Dose
Hyperglycemia

Keywords

  • Cyclophosphamide
  • Germ cell tumors
  • Maximum tolerated doses

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

Cite this

Pilot study of cisplatin, etoposide, bleomycin, and escalating dose cyclophosphamide therapy for children with high risk germ cell tumors : A report of the children's oncology group (COG). / Malogolowkin, Marcio; Krailo, Mark; Marina, Neyssa; Olson, Thomas; Frazier, A. Lindsay.

In: Pediatric Blood and Cancer, Vol. 60, No. 10, 01.10.2013, p. 1602-1605.

Research output: Contribution to journalArticle

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abstract = "Background: To establish the maximum tolerated dose (MTD) and toxicity profile of cyclophosphamide with cisplatin, etoposide, and bleomycin (C-PEB) in children with high-risk malignant germ cell tumors (HR-MGCT). Procedure: Eligibility criteria included untreated patients≤21 years of age with stage III/IV extragonadal, extra cranial MGCT. Patients received four cycles (repeated every 3 weeks) of cisplatin (20mg/m2/day×5 days), etoposide (100mg/m2/day×5 days), and bleomycin (15mg/m2 on Day 1) with escalating doses of cyclophosphamide on Day 1, assigned at the time of enrollment (1.2, 1.8, or 2.4g/m2). Patients with complete response had therapy discontinued. Patients with residual disease underwent second-look surgery, those with pathologic evidence of residual MGCT or whose markers had not normalized received two more cycles. All other patients had protocol therapy stopped. Results: Nineteen patients were enrolled between July 2004 and August 2007. Three patients were non-evaluable. Sixteen patients completed four cycles. Eleven had complete response, one had progressive disease and four had partial response. All four with partial response underwent second look surgery followed by two more cycles. Only one patient, on dose 1.8g/m2, experienced dose-limiting toxicity (DLT) during the first cycle of therapy (grade 3 hyperglycemia). The 4-year EFS and OS (± standard deviation) were 74±7{\%} and 89±10{\%}, respectively. Conclusion: The addition of cyclophosphamide to the standard PEB regimen (cisplatin, etoposide, and bleomycin) is feasible and well-tolerated at all dose levels used on this study. Pediatr Blood Cancer 2013;60:1602-1605.",
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