title: Phase II trial of irinotecan and metronomic temozolomide in patients with recurrent glioblastoma.
abstract: This phase II study was conducted to determine the efficacy and safety of metronomic temozolomide (TMZ) in combination with irinotecan in glioblastoma (GB) at first relapse. Patients with GB at first relapse received TMZ 50 mg/m/2day divided into three doses, except for a single 100 mg/m2 dose, administered between 3 and 6 h before every irinotecan infusion. Irinotecan was given intravenously at the previously established dose of 100 mg/m2 on days 8 and 22 of 28-day cycles. Treatment was given for a maximum of nine cycles or until progression or unacceptable toxicity occurred. Vascular endothelial growth factor and its soluble receptor 1, thrombospondin-1, microparticles, and microparticle-dependent procoagulant activity were measured in blood before treatment. The primary objective was 6-month progression-free survival (PFS). Twenty-seven evaluable patients were enrolled. Six-month PFS was 20.8%. Median PFS was 11.6 weeks (95% confidence interval: 7.5-15.7). Stable disease was the best response for nine (37.5%) patients, with a median duration of 11.2 weeks (4.2-35.85 weeks). No differences in PFS or response were observed among patients who relapsed during or after completion of adjuvant TMZ. Grade 3/4 adverse events included lymphopenia (15%), fatigue, diarrhea and febrile neutropenia (3.7% each), lymphopenia, neutropenia, and nausea/vomiting (11.1% each). One patient died from pneumonia and one patient died from pulmonary thromboembolism. Pretreatment levels of angiogenesis biomarkers, microparticles, and microparticle-related procoagulant activity were elevated in patients compared with healthy volunteers. This regimen is feasible, but failed to improve the results obtained with other second-line therapies in recurrent GB.
authors.affiliation: aDepartment of Medical Oncology bResearch Center, Hospital Universitari i Politècnic La Fe cDepartment of Hematology and Medical Oncology, Hospital Clínico Universitario de Valencia, Valencia dDepartment of Medical Oncology, Institut Català d'Oncologia, Badalona eDepartment of Medical Oncology, Hospital Clínico Universitario San Carlos fDepartment of Medical Oncology, Hospital Universitario Ramón y Cajal gDepartment of Medical Oncology, Hospital General Universitario Gregorio Marañón, Madrid hDepartment of Medical Oncology, Hospital Regional Universitario Carlos Haya, Málaga iDepartment of Medical Oncology, Hospital Sant Pau jDepartment of Medical Oncology, Institut Català d'Oncologia-IDIBELL, l'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Gaspar
authors.initials: G
authors.lastname: Reynés
authors.forename: Vicenta
authors.initials: V
authors.lastname: Martínez-Sales
authors.forename: Virtudes
authors.initials: V
authors.lastname: Vila
authors.forename: Carmen
authors.initials: C
authors.lastname: Balañá
authors.forename: Pedro
authors.initials: P
authors.lastname: Pérez-Segura
authors.forename: María A
authors.initials: MA
authors.lastname: Vaz
authors.forename: Manuel
authors.initials: M
authors.lastname: Benavides
authors.forename: Oscar
authors.initials: O
authors.lastname: Gallego
authors.forename: Isabel
authors.initials: I
authors.lastname: Palomero
authors.forename: Miguel
authors.initials: M
authors.lastname: Gil-Gil
authors.forename: Tania
authors.initials: T
authors.lastname: Fleitas
authors.forename: Encarnación
authors.initials: E
authors.lastname: Reche
mesh_terms: D059250:Administration, Metronomic; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D000077204:Temozolomide
chemical_list: D000077146:Irinotecan; D003606:Dacarbazine; D002166:Camptothecin; D000077204:Temozolomide