title: A phase 2 trial of verubulin for recurrent glioblastoma: a prospective study by the Brain Tumor Investigational Consortium (BTIC).
abstract: Treatment options are limited for recurrent glioblastoma (GBM). Verubulin is a microtubule destabilizer and vascular disrupting agent that achieve high brain concentration relative to plasma in animals. Adults with recurrent GBM who failed prior standard therapy were eligible. The primary endpoint was 1-month progression-free survival (PFS-1) for bevacizumab refractory (Group 2) and 6-month progression-free survival (PFS-6) for bevacizumab naïve patients (Group 1). Verubulin was administered at 3.3 mg/m(2) as a 2-h intravenous infusion once weekly for 3 consecutive weeks in a 4-week cycle. The planned sample size was 34 subjects per cohort. 56 patients (37 men, 19 women) were enrolled, 31 in Group 1 and 25 in Group 2. The PFS-6 for Group 1 was 14% and the PFS-1 for Group 2 was 20%. Median survival from onset of treatment was 9.5 months in Group 1 and 3.4 months in Group 2. Best overall response was partial response (n = 3; 10% in Group 1; n = 1; 4.2% in Group 2) and stable disease (n = 7; 23% in Group 1; n = 5; 21% in Group 2). In Group 1, 38.7% of patients experienced a serious adverse event; however only 3.2% were potentially attributable to study drug. In Group 2, 44% of patients experienced a serious adverse event although none were attributable to study drug. Accrual was terminated early for futility. Single agent verubulin, in this dose and schedule, is well tolerated, associated with moderate but tolerable toxicity but has limited activity in either bevacizumab naïve or refractory recurrent GBM.
authors.affiliation: Seattle Cancer Care Alliance, Fred Hutchinson Cancer Center, University of Washington, 825 Eastlake Ave E, MS: G4-940, Seattle, WA, 98109, USA. chambemc@u.washington.edu.
authors.forename: Marc C
authors.initials: MC
authors.lastname: Chamberlain
authors.affiliation: Department of Neurology, Northwestern University, 710 N Lake Shore Drive, Abbott Hall, Room 1110, Chicago, IL, 60611, USA.
authors.forename: Sean
authors.initials: S
authors.lastname: Grimm
authors.affiliation: Cedars Sinai Medical Center, 8631 W 3rd St, Ste 410-E, Los Angeles, CA, 90048, USA.
authors.forename: Surasak
authors.initials: S
authors.lastname: Phuphanich
authors.affiliation: Stanford University, 875 Blake Wilbur Dr Rm 2221, Palo Alto, CA, 943042205, USA.
authors.forename: Larry
authors.initials: L
authors.lastname: Recht
authors.affiliation: Tufts University, 750 Washington St, # 833, Boston, MA, 02111, USA.
authors.forename: Jay Z
authors.initials: JZ
authors.lastname: Zhu
authors.affiliation: Jefferson University, 900 Walnut Street, Suite 200, Philadelphia, PA, 19107, USA.
authors.forename: Lyndon
authors.initials: L
authors.lastname: Kim
authors.affiliation: Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, 9500 Euclid Avenue, Mailcode: NB40, Cleveland, OH, 44195, USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Rosenfeld
authors.affiliation: Hematology/Oncology Section, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH, 03756, USA.
authors.forename: Camilo E
authors.initials: CE
authors.lastname: Fadul
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D011446:Prospective Studies; D011799:Quinazolines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D011799:Quinazolines; D000068258:Bevacizumab; C522974:verubulin
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