title: A Phase I study of concurrent RMP-7 and carboplatin with radiation therapy 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 to these children, and a potential way to improve its efficacy is to add radiosensitizers. Carboplatin is antineoplastic and radiosensitizing; however, its 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 objective of this Phase I study was to determine the toxicity and feasibility of delivering RMP-7 and carboplatin for 5 successive days during radiotherapy to children with newly diagnosed, diffuse, intrinsic brainstem gliomas.
  
  
  METHODS
  RMP-7 was given prior to the end of carboplatin infusion. Local radiotherapy, in dose fractions of 180 centigrays (cGy) per day (to a total dose of 5940 cGy), was given within 4 hours of completion of drug delivery. Duration of treatment was escalated in a stepwise, weekly fashion in cohorts of 3 patients, until there was treatment-limiting toxicity or until radiotherapy was completed. Thirteen patients were treated, and their median age was 7 years (age range, 3-12 yrs).
  
  
  RESULTS
  One child died early during treatment of progressive disease and was not assessable for toxicity. Treatment for 3 weeks, 4 weeks, and 5 weeks was tolerated well, with mild flushing, tachycardia, nausea, emesis, dizziness, and abdominal pain. One of 3 children treated at the full duration of therapy (33 doses over 7 weeks) developed dose-limiting hepatotoxicity and neutropenia. The estimated median survival was 328 days, and 1 patient remained free of disease progression for > 400 days after the initiation of treatment.
  
  
  CONCLUSIONS
  The results of this study confirmed the feasibility of giving RMP-7 and carboplatin daily during radiotherapy to children with brainstem tumors.
authors.affiliation: Center for Neuroscience and Behavioral Medicine, 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: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D020295:Brain Stem Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D016190:Carboplatin / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D011878:Radiotherapy / Q000009:adverse effects; D011879:Radiotherapy Dosage; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: C089876:RMP 7; D016190:Carboplatin; D001920:Bradykinin