title: A phase I study of irinotecan in combination with metronomic temozolomide in patients with recurrent glioblastoma.
abstract: To determine the maximum tolerated dose of irinotecan administered every 2 weeks, in combination with a fixed and continuous administration of temozolomide, in patients with glioblastoma at first relapse. Patients received oral temozolomide at a fixed and continuous dose of 50 mg/m divided into three daily doses, except for a single 100 mg/m dose, administered before every irinotecan infusion. Irinotecan was given intravenously on days 8 and 22 of 28-day cycles. The starting dose of irinotecan was 100 mg/m, and this was escalated by increments of 15 mg/m in cohorts of 3-6 evaluable patients. Determination of the dose-limiting toxicity was based on toxicities recorded from day 1 of the first cycleto day 8 of the third cycle. Enzyme-inducing antiepileptic drugs were not allowed. Tumor response was assessed by MRI every 8 weeks. Twelve patients were enrolled in this phase I study. The three patients enrolled at dose level 1 and six of nine patients enrolled at dose level 2 were evaluable for toxicity. The maximum tolerated dose of irinotecan was 100 mg/m. The dose-limiting toxicities were hematologic and gastrointestinal. Nine patients were evaluable for response: one patient achieved a partial response, four patients remained stable, and four patients had disease progression. The combination of metronomic temozolomide and irinotecan every 2 weeks can be safely administered at the recommended doses; a phase II study with this combination was started and has completed accrual.
authors: aDepartment of Medical Oncology, Hospital Universitari i Politècnic La Fe, Valencia bDepartment of Medical Oncology, Institut Català d'Oncologia, Badalona cDepartment of Medical Oncology, Hospital Sant Pau, Barcelona dDepartment of Medical Oncology, Hospital Universitario Virgen del Rocío, Sevilla eDepartment of Medical Oncology, Hospital Clínico San Carlos fDepartment of Medical Oncology, Hospital Universitario Ramón y Cajal, Madrid, Spain.
authors: Gaspar
authors: G
authors: Reynés
authors: Carmen
authors: C
authors: Balañá
authors: Oscar
authors: O
authors: Gallego
authors: Luis
authors: L
authors: Iglesias
authors: Pedro
authors: P
authors: Pérez
authors: José L
authors: JL
authors: García
mesh_terms: D059250:Administration, Metronomic; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D016543:Central Nervous System Neoplasms / Q000188:drug therapy*; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D000077146:Irinotecan; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D000077204:Temozolomide
chemical_list: D000077146:Irinotecan; D003606:Dacarbazine; D002166:Camptothecin; D000077204:Temozolomide