title: Phase I study pilot arms of radiotherapy and carmustine with temozolomide for anaplastic astrocytoma (Radiation Therapy Oncology Group 9813): implications for studies testing initial treatment of brain tumors.
abstract: OBJECTIVE
  To determine the safety and toxicity of carmustine (BCNU) and temozolomide (TMZ) with radiotherapy (RT) in newly diagnosed anaplastic astrocytoma.
  
  
  METHODS
  Patients >18 years old with anaplastic astrocytoma, a Karnofsky performance status score of > or =60, and adequate pulmonary function were eligible. All patients provided informed consent. Standard RT started within 5 weeks of diagnosis. In both arms, 150 mg/m(2) of TMZ was given on Days 1-5 of RT. In Arm 1, 200 mg/m(2) of carmustine was given on Day 1 of RT. In Arm 2, 150 mg/m(2) of carmustine was given on Day 5 of RT. After RT, TMZ and carmustine were repeated for a total of six cycles.
  
  
  RESULTS
  A total of 15 and 14 patients were enrolled in the two pilot arms. Because of hematologic and pulmonary toxicities, dose reductions by the second cycle of therapy occurred in >70% of the patients in Arm 1 and >50% in Arm 2 despite a reduction in the carmustine dose.
  
  
  CONCLUSIONS
  The results of these pilot studies have implications for the design of studies testing the initial treatment of brain tumors. Because of the poor tolerance of the combination, the multicooperative group Phase III study consists of two randomized arms of single-agent carmustine vs. single-agent TMZ.
authors.affiliation: Department of Neurological Surgery, University of California San Francisco, School of Medicine, 400 Parnassus Avenue A808, San Francisco, CA 94143, USA. changs@neurosurg.ucsf.edu
authors.forename: Susan M
authors.initials: SM
authors.lastname: Chang
authors.forename: Wendy
authors.initials: W
authors.lastname: Seiferheld
authors.forename: Walter
authors.initials: W
authors.lastname: Curran
authors.forename: R
authors.initials: R
authors.lastname: Share
authors.forename: J
authors.initials: J
authors.lastname: Atkins
authors.forename: Ali
authors.initials: A
authors.lastname: Choucair
authors.forename: J
authors.initials: J
authors.lastname: Kresl
authors.forename: Louisa
authors.initials: L
authors.lastname: Thoron
authors.forename: Gregory
authors.initials: G
authors.lastname: Cairncross
authors.forename: Mark
authors.initials: M
authors.lastname: Gilbert
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Bahary
authors.forename: Carol
authors.initials: C
authors.lastname: Dolinskas
authors.forename: David N
authors.initials: DN
authors.lastname: Louis
authors.forename: Peter
authors.initials: P
authors.lastname: Bushunow
authors.forename: Jan
authors.initials: J
authors.lastname: Buckner
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Barger
authors.forename: Minesh
authors.initials: M
authors.lastname: Mehta
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D001254:Astrocytoma / Q000188:drug therapy* / Q000532:radiotherapy*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D002330:Carmustine / Q000008:administration & dosage / Q000009:adverse effects; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D000077204:Temozolomide
chemical_list: D003606:Dacarbazine; D002330:Carmustine; D000077204:Temozolomide