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

Purpose : 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. Patients and Methods: From 1994 to 2000,375 patients were randomly assigned to receive radiotherapy and cycles of ACNU go mg/m(2) intravenously (IV) on day 1 and VM26 60 mg/m(2) IV on days 1 to 3 (n = 183), or ACNU 90 mg/m(2) IV on day 1 and Ara-C 120 mg/m(2) 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. Conclusion: 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. (C) 2003 by American Society of Clinical Oncology.