Neuro-Oncology Working Group 01 trial of nimustine plus teniposide versus nimustine plus cytarabine chemotherapy in addition to involved-field radiotherapy in the first-line treatment of malignant glioma.
OBJECTIVE
The role of chemotherapy in the primary treatment of malignant glioma remains controversial. The results from the German-Austrian Glioma trial (GAG, 1983 to 1988) demonstrated a survival benefit for chemotherapy using carmustine (BCNU) plus teniposide (VM26) over BCNU alone in addition to radiotherapy in patients with a Karnofsky performance score (KPS) more than 60. The Neuro-Oncology Working Group (NOA) of the German Cancer Society therefore compared the efficacy of nimustine (ACNU) plus VM26 and ACNU plus cytarabine (Ara-C) chemotherapy in addition to standard radiotherapy in patients with newly diagnosed malignant glioma.


METHODS
From 1994 to 2000, 375 patients were randomly assigned to receive radiotherapy and cycles of ACNU 90 mg/m2 intravenously (IV) on day 1 and VM26 60 mg/m2 IV on days 1 to 3 (n = 183), or ACNU 90 mg/m2 IV on day 1 and Ara-C 120 mg/m2 IV on days 1 to 3 (n = 179), in 6-week intervals. Thirteen patients were not eligible after central neuropathology review. The remaining 362 patients had glioblastoma (n = 301) or anaplastic glioma (n = 61).


RESULTS
Median survival and 2-year survival rates were 17.3 months and 25% for ACNU plus VM26, and 15.7 months and 29% for ACNU plus Ara-C in glioblastoma, and 60 months and 88% for ACNU plus VM26 and 62.5 months and 72% for ACNU plus Ara-C in anaplastic glioma. Multivariate analysis revealed no survival advantage for either arm or for subpopulations defined by histology, age, or KPS. Hematologic toxicity was more prominent in the ACNU plus Ara-C arm.


CONCLUSIONS
The median survival times and 2-year survival rates for patients with anaplastic glioma and glioblastoma achieved in the NOA-01 trial compare favorably with historical trials and with the Radiation Therapy Oncology Group database. The toxicity profile favors ACNU plus VM26 for further evaluation.
Weller
Michael
M
Department of Neurology, University of Tübingen, Medical School, Hoppe-Seyler-Strasse 3, 72076 Tübingen, Germany. michael.weller@uni-tuebingen.de.
Müller
Bettina
B
Koch
Rainer
R
Bamberg
Michael
M
Krauseneck
Peter
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D018450:Disease Progression; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy / Q000532:radiotherapy; D005910:Glioma / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015376:Nimustine / Q000008:administration & dosage*; D011379:Prognosis; D011446:Prospective Studies; D016019:Survival Analysis; D013713:Teniposide / Q000008:administration & dosage*; D016896:Treatment Outcome
D015376:Nimustine; D013713:Teniposide