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

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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.

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Acknowledgments

We thank Jan Englehart for outstanding administrative and data management throughout the development and conduct of this trial. We are also grateful to Elizabeth Gilger, Maureen Gallagher, Heather Ward and Kristine Feld for outstanding patient care and conduct on this study. Grants from The Cure Starts Now Foundation and support from Genentech, in part, funded this study.

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Authors and Affiliations

  1. Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave MLC 7051, Cincinnati, OH, 45229, USA

    Trent R. Hummel, Ralph Salloum, Rachid Drissi, Shiva Kumar, Matthew Sobo, Adam Lane, Lionel M. Chow, Laurie Grimme, Renee Doughman, Lori Backus, Lili Miles, Charles Stevenson, Maryam Fouladi & Mariko DeWire

  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

    Stewart Goldman

  3. Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH, 45229, USA

    Ahna Pai

  4. Division of Radiology, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH, 45229, USA

    James Leach

  5. Division of Physical Medicine & Rehabilitation, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH, 45229, USA

    David Pruitt

  6. Division of Neurology, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH, 45229, USA

    Mary Sutton

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  1. Trent R. Hummel
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  2. Ralph Salloum
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Correspondence to Trent R. Hummel.

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Genentech funded, in part, a portion of this study.

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Hummel, T.R., Salloum, R., Drissi, R. et al. A pilot study of bevacizumab-based therapy in patients with newly diagnosed high-grade gliomas and diffuse intrinsic pontine gliomas. J Neurooncol 127, 53–61 (2016). https://doi.org/10.1007/s11060-015-2008-6

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  • DOI: https://doi.org/10.1007/s11060-015-2008-6

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