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

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 adul...

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Bibliographic Details
Published in:	Journal of neuro-oncology Vol. 127; no. 1; pp. 53 - 61
Main Authors:	Hummel, Trent R., Salloum, Ralph, Drissi, Rachid, Kumar, Shiva, Sobo, Matthew, Goldman, Stewart, Pai, Ahna, Leach, James, Lane, Adam, Pruitt, David, Sutton, Mary, Chow, Lionel M., Grimme, Laurie, Doughman, Renee, Backus, Lori, Miles, Lili, Stevenson, Charles, Fouladi, Maryam, DeWire, Mariko
Format:	Journal Article
Language:	English
Published:	New York Springer US 01-03-2016 Springer Nature B.V
Subjects:	Adolescent Adult Antineoplastic Combined Chemotherapy Protocols - therapeutic use Bevacizumab - administration & dosage Brain Stem Neoplasms - diagnosis Brain Stem Neoplasms - therapy Camptothecin - administration & dosage Camptothecin - analogs & derivatives Chemoradiotherapy Child Child, Preschool Clinical Study Dacarbazine - administration & dosage Dacarbazine - analogs & derivatives Female Follow-Up Studies Glioma - diagnosis Glioma - therapy Humans Male Medicine Medicine & Public Health Neoplasm Grading Neurology Oncology Pilot Projects Prognosis Survival Rate Young Adult High-grade glioma Children Diffuse intrinsic pontine glioma Bevacizumab
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Summary:	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/m 2 /day for 42 days) followed by bevacizumab (10 mg/kg, days 1, 15), irinotecan (125 mg/m 2 , days 1, 15) and temozolomide (150 mg/m 2 /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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0167-594X 1573-7373
DOI:	10.1007/s11060-015-2008-6