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

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• 作者：Trent R. Hummel ; Ralph Salloum ; Rachid Drissi ; Shiva Kumar…
• 关键词：Bevacizumab ; Diffuse intrinsic pontine glioma ; High ; grade glioma ; Children
• 刊名：Journal of Neuro-Oncology
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：127
• 期：1
• 页码：53-61
• 全文大小：406 KB
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• 作者单位：Trent R. Hummel (1)
  Ralph Salloum (1)
  Rachid Drissi (1)
  Shiva Kumar (1)
  Matthew Sobo (1)
  Stewart Goldman (2)
  Ahna Pai (3)
  James Leach (4)
  Adam Lane (1)
  David Pruitt (5)
  Mary Sutton (6)
  Lionel M. Chow (1)
  Laurie Grimme (1)
  Renee Doughman (1)
  Lori Backus (1)
  Lili Miles (1)
  Charles Stevenson (1)
  Maryam Fouladi (1)
  Mariko DeWire (1)
  
  1. Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave MLC 7051, Cincinnati, OH, 45229, USA
  2. Division of Hematology/Oncology, Ann and Robert H Lurie Children’s Hospital of Chicago, 225 E Chicago Ave, Box 30, Chicago, IL, 60611, USA
  3. Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH, 45229, USA
  4. Division of Radiology, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH, 45229, USA
  5. Division of Physical Medicine & Rehabilitation, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH, 45229, USA
  6. Division of Neurology, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH, 45229, USA
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Oncology
  
• 出版者：Springer Netherlands
• ISSN：1573-7373

文摘

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.