title: Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. Temodal Brain Tumor Group.
abstract: OBJECTIVE
  To determine the antitumor efficacy and safety profile of temozolomide in patients with malignant astrocytoma at first relapse.
  
  
  METHODS
  This open-label, multicenter, phase II trial enrolled 162 patients (intent-to-treat [ITT] population). After central histologic review, 111 patients were confirmed to have had an anaplastic astrocytoma (AA) or anaplastic mixed oligoastrocytoma. Chemotherapy-naive patients were treated with temozolomide 200 mg/m(2)/d. Patients previously treated with chemotherapy received temozolomide 150 mg/m(2)/d; the dose could be increased to 200 mg/m(2)/d in the absence of grade 3/4 toxicity. Therapy was administered orally on the first 5 days of a 28-day cycle.
  
  
  RESULTS
  Progression-free survival (PFS) at 6 months, the primary protocol end point, was 46% (95% confidence interval, 38% to 54%). The median PFS was 5.4 months, and PFS at 12 months was 24%. The median overall survival was 13.6 months, and the 6- and 12-month survival rates were 75% and 56%, respectively. The objective response rate determined by independent central review of gadolinium-enhanced magnetic resonance imaging scans of the ITT population was 35% (8% complete response [CR], 27% partial response [PR]), with an additional 26% of patients with stable disease (SD). The median PFS for patients with SD was 4.4 months, with 33% progression-free at 6 months. Maintenance of progression-free status and objectively assessed response (CR/PR/SD) were both associated with health-related quality-of-life (HQL) benefits. Adverse events were mild to moderate, with hematologic side effects occurring in less than 10% of patients.
  
  
  CONCLUSIONS
  Temozolomide demonstrated good single-agent activity, an acceptable safety profile, and documented HQL benefits in patients with recurrent AA.
authors.affiliation: University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. yung@manderson.org
authors.forename: W K
authors.initials: WK
authors.lastname: Yung
authors.forename: M D
authors.initials: MD
authors.lastname: Prados
authors.forename: R
authors.initials: R
authors.lastname: Yaya-Tur
authors.forename: S S
authors.initials: SS
authors.lastname: Rosenfeld
authors.forename: M
authors.initials: M
authors.lastname: Brada
authors.forename: H S
authors.initials: HS
authors.lastname: Friedman
authors.forename: R
authors.initials: R
authors.lastname: Albright
authors.forename: J
authors.initials: J
authors.lastname: Olson
authors.forename: S M
authors.initials: SM
authors.lastname: Chang
authors.forename: A M
authors.initials: AM
authors.lastname: O'Neill
authors.forename: A H
authors.initials: AH
authors.lastname: Friedman
authors.forename: J
authors.initials: J
authors.lastname: Bruner
authors.forename: N
authors.initials: N
authors.lastname: Yue
authors.forename: M
authors.initials: M
authors.lastname: Dugan
authors.forename: S
authors.initials: S
authors.lastname: Zaknoen
authors.forename: V A
authors.initials: VA
authors.lastname: Levin
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D001254:Astrocytoma / Q000188:drug therapy* / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D011788:Quality of Life; D016019:Survival Analysis; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide