A pediatric trial of radiation/cetuximab followed by irinotecan/cetuximab in newly diagnosed diffuse pontine gliomas and high-grade astrocytomas: A Pediatric Oncology Experimental Therapeutics Investigators' Consortium study

Margaret E. Macy, Mark W. Kieran, Susan N. Chi, Kenneth J. Cohen, Tobey J. MacDonald, Amy A. Smith, Michael M. Etzl, Michele C. Kuei, Andrew M. Donson, Lia Gore, Jennifer DiRenzo, Tanya M. Trippett, Irina Ostrovnaya, Aru Narendran, Nicholas K. Foreman, Ira J. Dunkel

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Diffuse intrinsic pontine gliomas (DIPGs) and high-grade astrocytomas (HGA) continue to have dismal prognoses. The combination of cetuximab and irinotecan was demonstrated to be safe and tolerable in a previous pediatric phase 1 combination study. We developed this phase 2 trial to investigate the safety and efficacy of cetuximab given with radiation therapy followed by adjuvant cetuximab and irinotecan. Methods: Eligible patients of age 3–21 years had newly diagnosed DIPG or HGA. Patients received radiation therapy (5,940 cGy) with concurrent cetuximab. Following radiation, patients received cetuximab weekly and irinotecan daily for 5 days per week for 2 weeks every 21 days for 30 weeks. Correlative studies were performed. The regimen was considered to be promising if the number of patients with 1-year progression-free survival (PFS) for DIPG and HGA was at least six of 25 and 14 of 26, respectively. Results: Forty-five evaluable patients were enrolled (25 DIPG and 20 HGA). Six patients with DIPG and five with HGA were progression free at 1 year from the start of therapy with 1-year PFS of 29.6% and 18%, respectively. Fatigue, gastrointestinal complaints, electrolyte abnormalities, and rash were the most common adverse events and generally of grade 1 and 2. Increased epidermal growth factor receptor copy number but no K-ras mutations were identified in available samples. Conclusions: The trial did not meet the predetermined endpoint to deem this regimen successful for HGA. While the trial met the predetermined endpoint for DIPG, overall survival was not markedly improved from historical controls, therefore does not merit further study in this population.

Original languageEnglish (US)
Article numbere26621
JournalPediatric Blood and Cancer
Volume64
Issue number11
DOIs
StatePublished - Nov 2017

Keywords

  • cetuximab
  • chemotherapy
  • diffuse intrinsic pontine glioma
  • pediatric high-grade astrocytoma
  • radiation

ASJC Scopus subject areas

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

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