title: Phase III randomized study of radiation and temozolomide versus radiation and nitrosourea therapy for anaplastic astrocytoma: results of NRG Oncology RTOG 9813.
abstract: The primary objective of this study was to compare the overall survival (OS) of patients with anaplastic astrocytoma (AA) treated with radiotherapy (RT) and either temozolomide (TMZ) or a nitrosourea (NU). Secondary endpoints were time to tumor progression (TTP), toxicity, and the effect of IDH1 mutation status on clinical outcome.
  
  
  
  Eligible patients with centrally reviewed, histologically confirmed, newly diagnosed AA were randomized to receive either RT+TMZ (n = 97) or RT+NU (n = 99). The study closed early because the target accrual rate was not met.
  
  
  
  Median follow-up time for patients still alive was 10.1 years (1.9-12.6 y); 66% of the patients died. Median survival time was 3.9 years in the RT/TMZ arm (95% CI, 3.0-7.0) and 3.8 years in the RT/NU arm (95% CI, 2.2-7.0), corresponding to a hazard ratio (HR) of 0.94 (P = .36; 95% CI, 0.67-1.32). The differences in progression-free survival (PFS) and TTP between the 2 arms were not statistically significant. Patients in the RT+NU arm experienced more grade ≥3 toxicity (75.8% vs 47.9%, P < .001), mainly related to myelosuppression. Of the 196 patients, 111 were tested for IDH1-R132H status (60 RT+TMZ and 51 RT+NU). Fifty-four patients were IDH negative and 49 were IDH positive with a better OS in IDH-positive patients (median survival time 7.9 vs 2.8 y; P = .004, HR = 0.50; 95% CI, 0.31-0.81).
  
  
  
  RT+TMZ did not appear to significantly improve OS or TTP for AA compared with RT+ NU. RT+TMZ was better tolerated. IDH1-R132H mutation was associated with longer survival.
authors.affiliation: University of California San Francisco, San Francisco, California, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Chang
authors.affiliation: NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania, USA.
authors.forename: Peixin
authors.initials: P
authors.lastname: Zhang
authors.affiliation: University of Calgary, Calgary, Canada.
authors.forename: J Gregory
authors.initials: JG
authors.lastname: Cairncross
authors.affiliation: University of Texas-MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Gilbert
authors.affiliation: Centre Hospitalier de l`Université de Montréal-Notre Dame, Montréal, Canada.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Bahary
authors.affiliation: University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Dolinskas
authors.affiliation: Department of Radiation Oncology, The Ohio State University, Columbus, OH, USA.
authors.forename: Arnab
authors.initials: A
authors.lastname: Chakravarti
authors.affiliation: MacFeeters Hamilton Center for Neuro-Oncology, Toronto, Canada.
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Aldape
authors.affiliation: The Ohio State University Medical Center, Columbus, Ohio, USA.
authors.forename: Erica H
authors.initials: EH
authors.lastname: Bell
authors.affiliation: University of Virginia, Charlottesville, Virginia, USA.
authors.forename: David
authors.initials: D
authors.lastname: Schiff
authors.affiliation: Mayo Clinic, Jacksonville, Florida, USA.
authors.forename: Kurt
authors.initials: K
authors.lastname: Jaeckle
authors.affiliation: University of Texas-MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Brown
authors.affiliation: Wayne State University, Detroit, Michigan, USA.
authors.forename: Geoffrey R
authors.initials: GR
authors.lastname: Barger
authors.affiliation: Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Werner-Wasik
authors.affiliation: Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Helen
authors.initials: H
authors.lastname: Shih
authors.affiliation: Arizona Oncology Services Foundation, Phoenix, Arizona, USA.
authors.forename: David
authors.initials: D
authors.lastname: Brachman
authors.affiliation: University of Texas-MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Marta
authors.initials: M
authors.lastname: Penas-Prado
authors.affiliation: University of Wisconsin Hospital, Madison, Wisconsin, USA.
authors.forename: H Ian
authors.initials: HI
authors.lastname: Robins
authors.affiliation: Centre Hospitalier de l`Université de Montréal-Notre Dame, Montréal, Canada.
authors.forename: Karl
authors.initials: K
authors.lastname: Belanger
authors.affiliation: Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Schultz
authors.affiliation: Intermountain Medical Center, Murray, Utah, USA.
authors.forename: Grant
authors.initials: G
authors.lastname: Hunter
authors.affiliation: University of Maryland Medical Systems, Baltimore, Maryland, USA.
authors.forename: Minesh
authors.initials: M
authors.lastname: Mehta
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D001254:Astrocytoma / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009607:Nitrosourea Compounds / Q000627:therapeutic use*; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate; D000077204:Temozolomide; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D014408:Biomarkers, Tumor; D009607:Nitrosourea Compounds; D003606:Dacarbazine; D000077204:Temozolomide
keywords: anaplastic astrocytoma; nitrosourea; radiotherapy; temozolomide