title: Sunitinib administered prior to radiotherapy in patients with non-resectable glioblastoma: results of a phase II study.
abstract: Sunitinib is a tyrosine kinase inhibitor with direct anti-tumor and anti-angiogenesis activity targeting VEGFR 1-2, PDGFR α-β, c-kit, bFGF, (CSF-1), FLT3 and RET. The present trial examined the activity of sunitinib in 12 patients with newly diagnosed, non-resectable glioblastoma. Patients (≤75 years of age with performance status [PS] ≥2 and minimental status [MMS] ≥25) were treated post-biopsy with sunitinib 37.5 mg daily for 8 weeks pre-radiotherapy, during radiotherapy (60 Gy, 6 weeks) and post-radiotherapy until disease progression. The primary endpoints were overall response rate (ORR; RANO criteria) after 8 weeks of sunitinib and patient tolerance. Secondary endpoints were percentage of patients free of neurological deterioration pre-radiotherapy, percentage of patients completing radiotherapy, progression-free survival (PFS), overall survival (OS), and 1-year survival. A Simon 2-stage design (12 →20) based on ORR was applied to calculate the number of patients needed to detect at least 10 % response with α error of 0.05 and β error of 0.10. The trial was closed because it did not meet minimal activity criteria. ORR was 0 % with only 1/12 patients (8.3 %) achieving stable disease after sunitinib treatment. No patient showed reduction in gadolinium enhancement. The most frequent G3/4 toxicities were fatigue (24.9 %) and diarrhea (16.6 %); one patient died of a CNS hemorrhage; 10/12 patients (83.3 %) deteriorated neurologically before radiation therapy; median PFS was 7.7 weeks (95 % CI: 7.2-8.2); median OS was 12.8 weeks (95 % CI: 0.5-23.8 weeks); 1-year survival was 0 %. Sunitinib has no activity as monotherapy in glioblastoma, and further investigation of its efficacy in this setting is unwarranted.
authors.affiliation: Medical Oncology Service, Catalan Institute of Oncology (ICO), Hospital Germans Trias i Pujol, Carretera Canyet sn, 08916, Badalona, Spain, cbalana@iconcologia.net.
authors.forename: Carmen
authors.initials: C
authors.lastname: Balaña
authors.forename: Miguel J
authors.initials: MJ
authors.lastname: Gil
authors.forename: Pedro
authors.initials: P
authors.lastname: Perez
authors.forename: Gaspar
authors.initials: G
authors.lastname: Reynes
authors.forename: Oscar
authors.initials: O
authors.lastname: Gallego
authors.forename: Teresa
authors.initials: T
authors.lastname: Ribalta
authors.forename: Jaume
authors.initials: J
authors.lastname: Capellades
authors.forename: Sofia
authors.initials: S
authors.lastname: Gonzalez
authors.forename: Eugenia
authors.initials: E
authors.lastname: Verger
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001706:Biopsy; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D007211:Indoles / Q000008:administration & dosage*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000008:administration & dosage*; D011878:Radiotherapy / Q000379:methods; D000077210:Sunitinib; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib