title: A phase II single-arm study of irinotecan in combination with temozolomide (TEMIRI) in children with newly diagnosed high grade glioma: a joint ITCC and SIOPE-brain tumour study.
abstract: A multicenter, two stage phase II study, investigated irinotecan plus temozolomide in children with newly diagnosed high grade glioma. The primary endpoint was tumor response during a two-cycle treatment window, confirmed by external review committee. Patients received oral temozolomide 100 mg/(m(2) day) (days 1-5) and intravenous irinotecan 10 mg/(m(2) day) (days 1-5 and 8-12) for two 21-day cycles (three cycles for patients exhibiting objective tumor response). Standard treatment was then administered according to local investigator choice. In total 17 patients were enrolled and treated by local investigators. However, central pathology review found three patients did not have a diagnosis of high grade glioma and another four patients did not have evaluable disease according to independent central radiological review. The primary endpoint was based on the first ten evaluable patients as determined by the external review committee. Recruitment was stopped for futility after there were no complete or partial responses during the two-cycle treatment window in the first ten evaluable patients. Five patients had stable disease, and five progressed. Data for secondary endpoints including; time to tumor progression, time to treatment failure, and overall survival is reported. The safety profile of the treatment showed the combination was tolerable with two patients (11.8 %) having grade three nausea, and one (5.9 %) experiencing a grade four neutropenia, leading to permanent discontinuation from adjuvant treatment. Irinotecan plus temozolomide, although well tolerated did not improve outcome over historical controls in this setting.
authors: Paediatric Oncology Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK. darren.hargrave@nhs.net
authors: Darren
authors: D
authors: Hargrave
authors: Birgit
authors: B
authors: Geoerger
authors: Didier
authors: D
authors: Frappaz
authors: Torsten
authors: T
authors: Pietsch
authors: Lyle
authors: L
authors: Gesner
authors: Laura
authors: L
authors: Cisar
authors: Aurora
authors: A
authors: Breazna
authors: Andrew
authors: A
authors: Dorman
authors: Ofelia
authors: O
authors: Cruz-Martinez
authors: Jose Luis
authors: JL
authors: Fuster
authors: Xavier
authors: X
authors: Rialland
authors: Céline
authors: C
authors: Icher
authors: Pierre
authors: P
authors: Leblond
authors: David
authors: D
authors: Ashley
authors: Giorgio
authors: G
authors: Perilongo
authors: Martin
authors: M
authors: Elliott
authors: Martin
authors: M
authors: English
authors: Niels
authors: N
authors: Clausen
authors: Jacques
authors: J
authors: Grill
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D002648:Child; D002675:Child, Preschool; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D000077146:Irinotecan; D008297:Male; D060787:Neoplasm Grading; D000077204:Temozolomide; D016896:Treatment Outcome
chemical_list: D000077146:Irinotecan; D003606:Dacarbazine; D002166:Camptothecin; D000077204:Temozolomide