title: A randomized phase II trial of standard dose bevacizumab versus low dose bevacizumab plus lomustine (CCNU) in adults with recurrent glioblastoma.
abstract: Antiangiogenic therapy can rapidly reduce vascular permeability and cerebral edema but high doses of bevacizumab may induce selective pressure to promote resistance. This trial evaluated the efficacy of low dose bevacizumab in combination with lomustine (CCNU) compared to standard dose bevacizumab in patients with recurrent glioblastoma. Patients (N = 71) with recurrent glioblastoma who previously received radiation and temozolomide were randomly assigned 1:1 to receive bevacizumab monotherapy (10 mg/kg) or low dose bevacizumab (5 mg/kg) in combination with lomustine (90 mg/m(2)). The primary end point was progression-free survival (PFS) based on a blinded, independent radiographic assessment of post-contrast T1-weighted and non-contrast T2/FLAIR weighted magnetic resonance imaging (MRI) using RANO criteria. For 69 evaluable patients, median PFS was not significantly longer in the low dose bevacizumab + lomustine arm (4.34 months, CI 2.96-8.34) compared to the bevacizumab alone arm (4.11 months, CI 2.69-5.55, p = 0.19). In patients with first recurrence, there was a trend towards longer median PFS time in the low dose bevacizumab + lomustine arm (4.96 months, CI 4.17-13.44) compared to the bevacizumab alone arm (3.22 months CI 2.5-6.01, p = 0.08). The combination of low dose bevacizumab plus lomustine was not superior to standard dose bevacizumab in patients with recurrent glioblastoma. Although the study was not designed to exclusively evaluate patients at first recurrence, a strong trend towards improved PFS was seen in that subgroup for the combination of low dose bevacizumab plus lomustine. Further studies are needed to better identify such subgroups that may most benefit from the combination treatment.
authors.affiliation: Department of Neuro-Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 431, Houston, TX, 77030, USA. sweathers@mdanderson.org.
authors.forename: Shiao-Pei
authors.initials: SP
authors.lastname: Weathers
authors.affiliation: University of Alabama at Birmingham, 1020 Faculty Office Tower, 510 20th Street South, Birmingham, AL, 35294, USA.
authors.forename: Xiaosi
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Biostatistics, University of MD Anderson Cancer Center, 1400 Pressler St., Houston, TX, 77030, USA.
authors.forename: Diane D
authors.initials: DD
authors.lastname: Liu
authors.affiliation: Department of Neuro-Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 431, Houston, TX, 77030, USA.|Texas Oncology, 901 W. 38th Street, Austin, TX, 78705, USA.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Conrad
authors.affiliation: Department of Neuro-Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 431, Houston, TX, 77030, USA.|National Institutes of Health, 9030 Old Georgetown Rd., Bethesda, MD, 20892, USA.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Gilbert
authors.affiliation: Department of Neuro-Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 431, Houston, TX, 77030, USA.
authors.forename: Monica E
authors.initials: ME
authors.lastname: Loghin
authors.affiliation: Department of Neuro-Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 431, Houston, TX, 77030, USA.
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: O'Brien
authors.affiliation: Department of Neuro-Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 431, Houston, TX, 77030, USA.
authors.forename: Marta
authors.initials: M
authors.lastname: Penas-Prado
authors.affiliation: Department of Neuro-Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 431, Houston, TX, 77030, USA.|M410 Starling Loving Hall, 320 W., 10th Avenue, Columbus, OH, 43210, USA.
authors.forename: Vinay K
authors.initials: VK
authors.lastname: Puduvalli
authors.affiliation: Department of Neuro-Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 431, Houston, TX, 77030, USA.|Department of Neurosurgery, Houston Methodist Hospital, 6560 Fannin, Scurlock Suite 900, Houston, TX, 77030, USA.
authors.forename: Ivo
authors.initials: I
authors.lastname: Tremont-Lukats
authors.affiliation: Department of Neuroradiology, University of Texas MD Anderson Cancer Center, 1400 Pressler St Unit 1482, Houston, TX, 77030, USA.
authors.forename: Rivka R
authors.initials: RR
authors.lastname: Colen
authors.affiliation: Department of Neuro-Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 431, Houston, TX, 77030, USA.
authors.forename: W K Alfred
authors.initials: WKA
authors.lastname: Yung
authors.affiliation: Department of Neuro-Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 431, Houston, TX, 77030, USA.
authors.forename: John F
authors.initials: JF
authors.lastname: de Groot
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality; D004305:Dose-Response Relationship, Drug; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D017567:Karnofsky Performance Status; D008130:Lomustine / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D000068258:Bevacizumab; D008130:Lomustine
keywords: Angiogenesis; Bevacizumab; Glioblastoma; Lomustine; VEGF