title: Continuous daily sunitinib for recurrent glioblastoma.
abstract: Bevacizumab ((BEV) has become a mainstay of treating recurrent glioblastoma, but eventual tumor resistance is expected. Targeting multiple growth-associated signaling pathways may result in more effective treatment than targeting VEGF alone. Patients with recurrent glioblastoma were stratified by prior BEV exposure and treated with sunitinib 37.5 mg daily in this phase II study. Response evaluations were performed at baseline and at the end of every 4 week cycle. Six-month progression-free survival (PFS6) was the primary endpoint for both arms of the study. Secondary endpoints included health related quality of life measures and FDG-PET correlatives with patient outcomes. Sixty-three patients were accrued to this study; thirty-two were BEV-naïve, 31 were BEV-resistant. PFS6 was 10.4 % [95 % CI 3.2-33.8] in the BEV-naïve cohort and 0 % in the BEV-resistant cohort. Median overall survival was 9.4 months [95 % CI 6.15-21.90] in the BEV-naïve cohort and 4.37 months [95 % CI 3.02-6.21] in the BEV-resistant cohort. 3/29 patients (10 %) of the BEV-naïve, and 0/27 BEV-resistant patients achieved radiographic response. Thrombocytopenia, leukopenia, and neutropenia were the most common drug-associated adverse events and occurred with higher frequency than expected. Sunitinib treatment in BEV-naïve patients did not appear to affect outcomes with subsequent BEV therapy. Continuous daily sunitinib did not prolong progression-free survival in BEV-naïve nor BEV-resistant patients with recurrent glioblastoma.
authors.affiliation: Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, 9030 Old Georgetown Road, #225, Bethesda, MD 20892, USA. kreislt@mail.nih.gov
authors.forename: Teri Nguyen
authors.initials: TN
authors.lastname: Kreisl
authors.forename: Perry
authors.initials: P
authors.lastname: Smith
authors.forename: Joohee
authors.initials: J
authors.lastname: Sul
authors.forename: Carlos
authors.initials: C
authors.lastname: Salgado
authors.forename: Fabio M
authors.initials: FM
authors.lastname: Iwamoto
authors.forename: Joanna H
authors.initials: JH
authors.lastname: Shih
authors.forename: Howard A
authors.initials: HA
authors.lastname: Fine
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D011758:Pyrroles / Q000627:therapeutic use*; D011788:Quality of Life; D000077210:Sunitinib; D015996:Survival Rate
chemical_list: D020533:Angiogenesis Inhibitors; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib