title: Phase 1 study of concurrent RMP-7 and carboplatin with radiotherapy for children with newly diagnosed brainstem gliomas.
abstract: BACKGROUND
  Ninety percent of children with diffuse intrinsic brainstem tumors will die within 18 months of diagnosis. Radiotherapy is of transient benefit, and one way to potentially improve its efficacy is to add radiosensitizers. Carboplatin is antineoplastic and radiosensitizing. However, delivery to the primary tumor site is problematic. RMP-7 is a bradykinin analog that causes selective permeability of the blood-brain-tumor interface. The goal of the current Phase I study was to determine the toxicity and feasibility of delivering RMP-7 and carboplatin for 5 successive days during radiotherapy.
  
  
  METHODS
  RMP-7 was given before the end of carboplatin infusion. Local radiotherapy (5940 centigrays) was given within 4 hours of completion of drug delivery. Duration of treatment was escalated in a stepwise, weekly fashion, in cohorts of 3, until there was treatment-limiting toxicity or until radiotherapy was completed. Thirteen patients were treated, whose median age was 7 years (range, 3-14 yrs).
  
  
  RESULTS
  One child died early in treatment of progressive disease and was not assessable for toxicity. Treatment for 3, 4, or 5 weeks was tolerated well, with mild flushing, tachycardia, nausea, emesis, dizziness, and abdominal pain. Of 3 children treated at the full duration of therapy (33 doses over 7 wks), 1 developed dose-limiting hepatotoxicity and neutropenia. The estimated median survival period was 328 days, and 1 patient remained disease progression free > 400 days from initiation of treatment.
  
  
  CONCLUSIONS
  The results of the current study confirmed the feasibility of giving RMP-7 and carboplatin daily during radiotherapy.
authors.affiliation: Division of Neurology, Children's National Medical Center, Washington, DC 20010, USA. rpacker@cnmc.org
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Packer
authors.forename: Mark
authors.initials: M
authors.lastname: Krailo
authors.forename: Minesh
authors.initials: M
authors.lastname: Mehta
authors.forename: Katherine
authors.initials: K
authors.lastname: Warren
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Allen
authors.forename: Regina
authors.initials: R
authors.lastname: Jakacki
authors.forename: Judith G
authors.initials: JG
authors.lastname: Villablanca
authors.forename: Akiko
authors.initials: A
authors.lastname: Chiba
authors.forename: Gregory
authors.initials: G
authors.lastname: Reaman
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001920:Bradykinin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D020295:Brain Stem Neoplasms / Q000401:mortality / Q000628:therapy*; D016190:Carboplatin / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D005910:Glioma / Q000401:mortality / Q000628:therapy*; D006801:Humans
chemical_list: C089876:RMP 7; D016190:Carboplatin; D001920:Bradykinin