A pilot study of bevacizumab-based therapy in patients with newly diagnosed high-grade gliomas and diffuse intrinsic pontine gliomas

Trent R. Hummel*, Ralph Salloum, Rachid Drissi, Shiva Kumar, Matthew Sobo, Stewart Goldman, Ahna Pai, James Leach, Adam Lane, David Pruitt, Mary Sutton, Lionel M. Chow, Laurie Grimme, Renee Doughman, Lori Backus, Lili Miles, Charles Stevenson, Maryam Fouladi, Mariko DeWire

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Although bevacizumab has not proven effective in adults with newly diagnosed high-grade gliomas (HGG), feasibility in newly diagnosed children with diffuse intrinsic pontine gliomas (DIPG) or HGG has not been reported in a prospective study. In a safety and feasibility study, children and young adults with newly diagnosed HGG received radiotherapy (RT) with bevacizumab (10 mg/kg: days 22, 36) and temozolomide (75–90 mg/m2/day for 42 days) followed by bevacizumab (10 mg/kg, days 1, 15), irinotecan (125 mg/m2, days 1, 15) and temozolomide (150 mg/m2/day days 1–5). DIPG patients did not receive temozolomide. Telomerase activity, quality of life (QOL), and functional outcomes were assessed. Among 27 eligible patients (15 DIPG, 12 HGG), median age 10 years (range 3–29 years), 6 discontinued therapy for toxicity: 2 during RT (grade 4 thrombocytopenia, grade 3 hepatotoxicity) and 4 during maintenance therapy (grade 3: thrombosis, hypertension, skin ulceration, and wound dehiscence). Commonest ≥grade 3 toxicities included lymphopenia, neutropenia and leukopenia. Grade 3 hypertension occurred in 2 patients. No intracranial hemorrhages occurred. For DIPG patients, median overall survival (OS) was 10.4 months. For HGG patients, 3-year progression free survival and OS were 33 % (SE ± 14 %) and 50 % (SE ± 14 %), respectively. All 3 tested tumor samples, demonstrated histone H3.3K27M (n = 2 DIPG) or G34R (n = 1 HGG) mutations. QOL scores improved over the course of therapy. A bevacizumab-based regimen is feasible and tolerable in newly diagnosed children and young adults with HGG and DIPG.

Original languageEnglish (US)
Pages (from-to)53-61
Number of pages9
JournalJournal of Neuro-Oncology
Volume127
Issue number1
DOIs
StatePublished - Mar 1 2016

Keywords

  • Bevacizumab
  • Children
  • Diffuse intrinsic pontine glioma
  • High-grade glioma

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

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