title: Phase II study of irinotecan in combination with temozolomide (TEMIRI) in children with recurrent or refractory medulloblastoma: a joint ITCC and SIOPE brain tumor study.
abstract: BACKGROUND
  This multicenter phase II study investigated temozolomide + irinotecan (TEMIRI) treatment in children with relapsed or refractory medulloblastoma.
  
  
  METHODS
  Patients received temozolomide 100-125 mg/m(2)/day (days 1-5) and irinotecan 10 mg/m(2)/day (days 1-5 and 8-12) every 3 weeks. The primary endpoint was tumor response within the first 4 cycles confirmed ≥4 weeks and assessed by an external response review committee (ERRC). In a 2-stage Optimum Simon design, ≥6 responses in the first 15 evaluable patients were required within the first 4 cycles for continued enrollment; a total of 19 responses from the first 46 evaluable patients was considered successful.
  
  
  RESULTS
  Sixty-six patients were treated. Seven responses were recorded during stage 1 and 15 in the first 46 ERRC evaluated patients (2 complete responses and 13 partial responses). The objective response rate during the first 4 cycles was 32.6% (95% confidence interval [CI], 19.5%-48.0%). Median duration of response was 27.0 weeks (7.7-44.1 wk). In 63 patients evaluated by local investigators, the objective response rate was 33.3% (95% CI, 22.0%-46.3%), and 68.3% (95% CI, 55.3%-79.4%) experienced clinical benefit. Median survival was 16.7 months (95% CI, 13.3-19.8). The most common grade 3 treatment-related nonhematologic adverse event was diarrhea (7.6%). Grade 3/4 treatment-related hematologic adverse events included neutropenia (16.7%), thrombocytopenia (12.1%), anemia (9.1%), and lymphopenia (9%).
  
  
  CONCLUSIONS
  The planned study primary endpoint was not met. However, its tolerability makes TEMIRI a suitable candidate chemotherapy backbone for molecularly targeted agents in future trials in this setting.
authors.affiliation: Institut Gustave Roussy, University Paris-Sud XI, Villejuif, France. grill@igr.fr
authors.forename: Jacques
authors.initials: J
authors.lastname: Grill
authors.forename: Birgit
authors.initials: B
authors.lastname: Geoerger
authors.forename: Lyle
authors.initials: L
authors.lastname: Gesner
authors.forename: Danuta
authors.initials: D
authors.lastname: Perek
authors.forename: Pierre
authors.initials: P
authors.lastname: Leblond
authors.forename: Adela
authors.initials: A
authors.lastname: Cañete
authors.forename: Isabelle
authors.initials: I
authors.lastname: Aerts
authors.forename: Luis
authors.initials: L
authors.lastname: Madero
authors.forename: Josep Sanchez
authors.initials: JS
authors.lastname: de Toledo Codina
authors.forename: Joris
authors.initials: J
authors.lastname: Verlooy
authors.forename: Edward
authors.initials: E
authors.lastname: Estlin
authors.forename: Laura
authors.initials: L
authors.lastname: Cisar
authors.forename: Aurora
authors.initials: A
authors.lastname: Breazna
authors.forename: Andrew
authors.initials: A
authors.lastname: Dorman
authors.forename: Simon
authors.initials: S
authors.lastname: Bailey
authors.forename: Gary
authors.initials: G
authors.lastname: Nicolin
authors.forename: Richard G
authors.initials: RG
authors.lastname: Grundy
authors.forename: Darren
authors.initials: D
authors.lastname: Hargrave
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002528:Cerebellar Neoplasms / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008527:Medulloblastoma / Q000188:drug therapy*; D000077204:Temozolomide
chemical_list: D000077146:Irinotecan; D003606:Dacarbazine; D002166:Camptothecin; D000077204:Temozolomide
keywords: TEMIRI; medulloblastoma; temozolomide