title: Response to bevacizumab, irinotecan, and temozolomide in children with relapsed medulloblastoma: a multi-institutional experience.
abstract: OBJECTIVE
  Chemotherapy for relapsed medulloblastoma has been inadequate, and most patients succumb to disease.
  
  
  METHODS
  We retrospectively reviewed nine cases of relapsed medulloblastoma treated with bevacizumab, irinotecan, ± temozolomide. Patients received one to three prior therapeutic regimens. Five patients received 10 mg/kg bevacizumab and 125-150 mg/m(2) irinotecan IV every 2 weeks, with temozolomide, starting at a median dose of 150 mg/m(2) orally for 5 days monthly. Two patients received bevacizumab and irinotecan, but not temozolomide, due to provider preference. Two of nine patients received 15 mg/kg bevacizumab IV, 90 mg/m(2) irinotecan orally for five consecutive days, 100 mg/m(2)/day temozolomide IV for 5 days, and 1.5 mg/m(2) vincristine IV, each administered every 21 days.
  
  
  RESULTS
  Median time to progression was 11 months. Median overall survival was 13 months. Objective tumor response at 3 months was 67 %, including six patients with partial response (PR) and three patients with stable disease (SD). At 6 months, objective response was 55 %, with two patients with PR and three with complete response. Additionally, one patient had SD and three had PD. Two patients remain alive and progression free at 15 and 55 months; another is alive with disease at 20 months. Toxicities included two patients with grade III neutropenia, two with grade III thrombocytopenia, one with grade III elevation of liver function tests, and one patient with grade III diarrhea.
  
  
  CONCLUSIONS
  The combination of bevacizumab and irinotecan, with or without temozolomide, produces objective responses with minimal toxicity in children with recurrent medulloblastoma. Prospective clinical trials are needed to evaluate the efficacy of this strategy.
authors.affiliation: Aflac Cancer & Blood Disorders Center, Children's Healthcare of Atlanta, Emory University School of Medicine, 5455 Meridian Mark Rd., NE, Suite 400, Atlanta, GA 30342, USA.
authors.forename: Dolly
authors.initials: D
authors.lastname: Aguilera
authors.forename: Claire
authors.initials: C
authors.lastname: Mazewski
authors.forename: Jason
authors.initials: J
authors.lastname: Fangusaro
authors.forename: Tobey J
authors.initials: TJ
authors.lastname: MacDonald
authors.forename: Rene Y
authors.initials: RY
authors.lastname: McNall-Knapp
authors.forename: Laura L
authors.initials: LL
authors.lastname: Hayes
authors.forename: Sungjin
authors.initials: S
authors.lastname: Kim
authors.forename: Robert C
authors.initials: RC
authors.lastname: Castellino
mesh_terms: D000293:Adolescent; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007223:Infant; D000077146:Irinotecan; D008297:Male; D008527:Medulloblastoma / Q000188:drug therapy*; D012008:Recurrence; D012189:Retrospective Studies; D000077204:Temozolomide; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D000077146:Irinotecan; D003606:Dacarbazine; D002166:Camptothecin; D000077204:Temozolomide