title: A pilot study of bevacizumab-based therapy in patients with newly diagnosed high-grade gliomas and diffuse intrinsic pontine gliomas.
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/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.
authors.affiliation: Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave MLC 7051, Cincinnati, OH, 45229, USA. trent.hummel@cchmc.org.
authors.forename: Trent R
authors.initials: TR
authors.lastname: Hummel
authors.affiliation: Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave MLC 7051, Cincinnati, OH, 45229, USA.
authors.forename: Ralph
authors.initials: R
authors.lastname: Salloum
authors.affiliation: Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave MLC 7051, Cincinnati, OH, 45229, USA.
authors.forename: Rachid
authors.initials: R
authors.lastname: Drissi
authors.affiliation: Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave MLC 7051, Cincinnati, OH, 45229, USA.
authors.forename: Shiva
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave MLC 7051, Cincinnati, OH, 45229, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Sobo
authors.affiliation: Division of Hematology/Oncology, Ann and Robert H Lurie Children's Hospital of Chicago, 225 E Chicago Ave, Box 30, Chicago, IL, 60611, USA.
authors.forename: Stewart
authors.initials: S
authors.lastname: Goldman
authors.affiliation: Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH, 45229, USA.
authors.forename: Ahna
authors.initials: A
authors.lastname: Pai
authors.affiliation: Division of Radiology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH, 45229, USA.
authors.forename: James
authors.initials: J
authors.lastname: Leach
authors.affiliation: Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave MLC 7051, Cincinnati, OH, 45229, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Lane
authors.affiliation: Division of Physical Medicine & Rehabilitation, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH, 45229, USA.
authors.forename: David
authors.initials: D
authors.lastname: Pruitt
authors.affiliation: Division of Neurology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH, 45229, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Sutton
authors.affiliation: Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave MLC 7051, Cincinnati, OH, 45229, USA.
authors.forename: Lionel M
authors.initials: LM
authors.lastname: Chow
authors.affiliation: Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave MLC 7051, Cincinnati, OH, 45229, USA.
authors.forename: Laurie
authors.initials: L
authors.lastname: Grimme
authors.affiliation: Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave MLC 7051, Cincinnati, OH, 45229, USA.
authors.forename: Renee
authors.initials: R
authors.lastname: Doughman
authors.affiliation: Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave MLC 7051, Cincinnati, OH, 45229, USA.
authors.forename: Lori
authors.initials: L
authors.lastname: Backus
authors.affiliation: Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave MLC 7051, Cincinnati, OH, 45229, USA.
authors.forename: Lili
authors.initials: L
authors.lastname: Miles
authors.affiliation: Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave MLC 7051, Cincinnati, OH, 45229, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Stevenson
authors.affiliation: Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave MLC 7051, Cincinnati, OH, 45229, USA.
authors.forename: Maryam
authors.initials: M
authors.lastname: Fouladi
authors.affiliation: Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave MLC 7051, Cincinnati, OH, 45229, USA.
authors.forename: Mariko
authors.initials: M
authors.lastname: DeWire
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D020295:Brain Stem Neoplasms / Q000175:diagnosis / Q000628:therapy*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D059248:Chemoradiotherapy; D002648:Child; D002675:Child, Preschool; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000175:diagnosis / Q000628:therapy*; D006801:Humans; D000077146:Irinotecan; D008297:Male; D060787:Neoplasm Grading; D010865:Pilot Projects; D011379:Prognosis; D015996:Survival Rate; D000077204:Temozolomide; D055815:Young Adult
chemical_list: D000068258:Bevacizumab; D000077146:Irinotecan; D003606:Dacarbazine; D002166:Camptothecin; D000077204:Temozolomide
keywords: Bevacizumab; Children; Diffuse intrinsic pontine glioma; High-grade glioma