Faculty Collaboration Database

Phase III randomized study of radiation and temozolomide versus radiation and nitrosourea therapy for anaplastic astrocytoma: results of NRG Oncology RTOG 9813. Neuro Oncol 2017 Feb 01;19(2):252-258

Date

12/21/2016

Pubmed ID

27994066

Pubmed Central ID

PMC5463834

DOI

10.1093/neuonc/now236

Scopus ID

2-s2.0-85019070871 (requires institutional sign-in at Scopus site)   58 Citations

Abstract

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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).

CONCLUSIONS: 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.

Author List

Chang S, Zhang P, Cairncross JG, Gilbert MR, Bahary JP, Dolinskas CA, Chakravarti A, Aldape KD, Bell EH, Schiff D, Jaeckle K, Brown PD, Barger GR, Werner-Wasik M, Shih H, Brachman D, Penas-Prado M, Robins HI, Belanger K, Schultz C, Hunter G, Mehta M

Author

Christopher J. Schultz MD Chair, Professor in the Radiation Oncology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Aged
Aged, 80 and over
Antineoplastic Agents, Alkylating
Astrocytoma
Biomarkers, Tumor
Brain Neoplasms
Chemoradiotherapy
Dacarbazine
Female
Follow-Up Studies
Humans
Male
Middle Aged
Neoplasm Staging
Nitrosourea Compounds
Prognosis
Prospective Studies
Survival Rate
Young Adult