title: Phase II trial of intravenous lobradimil and carboplatin in childhood brain tumors: a report from the Children's Oncology Group.
abstract: BACKGROUND
  [corrected] Lobradimil is a synthetic bradykinin analog that rapidly and transiently increases the permeability of the blood-brain barrier (BBB). The combination of lobradimil and carboplatin was studied in pediatric patients with primary brain tumors in a phase II trial, the primary endpoints of which were to estimate the response rate and time to disease progression.
  
  
  METHODS
  Patients were stratified by histology into five cohorts: brainstem glioma, high-grade glioma, low-grade glioma, medullobastoma/primitive neuroectodermal tumor (PNET), and ependymoma. Patients received carboplatin adaptively dosed to achieve a target AUC of 3.5 mg min/ml per day (7 mg.min/ml/cycle) intravenously over 15 min on 2 consecutive days and lobradimil 600 ng/kg ideal body weight/day on 2 consecutive days each 28 day cycle.
  
  
  RESULTS
  Forty-one patients, age 2-19 years, were enrolled; 38 patients, including 1 patient ultimately determined to have atypical neurocytoma, were evaluable for response. No objective responses were observed in the brainstem glioma (n=12) and high-grade glioma (n = 9) cohorts, although two patients with high-grade glioma had prolonged disease stabilization (>6 months). The study was closed for commercial reasons prior to achieving the accrual goals for the ependymoma (n = 8), medulloblastoma/PNET (n = 6) and low-grade glioma (n = 2) cohorts, although responses were observed in 1 patient with PNET and 2 patients with ependymoma.
  
  
  CONCLUSIONS
  The combination of lobradimil and carboplatin was inactive in childhood high-grade gliomas and brainstem gliomas.
authors.affiliation: National Cancer Institute/Neuro-Oncology Branch, Bethesda, MD 20892-8200, USA. warrenk@mail.nih.gov
authors.forename: K
authors.initials: K
authors.lastname: Warren
authors.forename: R
authors.initials: R
authors.lastname: Jakacki
authors.forename: B
authors.initials: B
authors.lastname: Widemann
authors.forename: A
authors.initials: A
authors.lastname: Aikin
authors.forename: M
authors.initials: M
authors.lastname: Libucha
authors.forename: R
authors.initials: R
authors.lastname: Packer
authors.forename: G
authors.initials: G
authors.lastname: Vezina
authors.forename: G
authors.initials: G
authors.lastname: Reaman
authors.forename: D
authors.initials: D
authors.lastname: Shaw
authors.forename: M
authors.initials: M
authors.lastname: Krailo
authors.forename: C
authors.initials: C
authors.lastname: Osborne
authors.forename: J
authors.initials: J
authors.lastname: Cehelsky
authors.forename: D
authors.initials: D
authors.lastname: Caldwell
authors.forename: J
authors.initials: J
authors.lastname: Stanwood
authors.forename: S M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: F M
authors.initials: FM
authors.lastname: Balis
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001920:Bradykinin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004334:Drug Administration Schedule; D006801:Humans; D007262:Infusions, Intravenous; D016896:Treatment Outcome
chemical_list: C089876:RMP 7; D016190:Carboplatin; D001920:Bradykinin