Abstract
Combination therapy with radiation and (1-4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)3-nitrosourea hydrochloride (ACNU) and/or N1-(2'-tetrahydrofuryl)-5-fluorouracil (5-FU) was given to 102 patients with malignant gliomas. The purpose of this study was to evaluate the efficacy of two treatment protocols after operative resection as compared with the control treatment, radiotherapy+5-FU. The three protocols were (A): adequate operation (OP)+radiation (R) (40-60 Grey/6-7 weeks)+ACNU [1-3 mg/kg, intravenously (IV) or intraarterially (IA), two times with a week interval, and repeated after 6 months]±OK-432 (2.0 “Klinische Einheit” or clinical unit/week, intramuscularly), (B): OP+R+ACNU (1-3 mg/kg, IV or IA, two times with 6-8 weeks interval, and repeated after 6 months)+5-FU (8-16 mg/kg/day orally)±OK-432, (C): OP+R+5-FU.
The combination therapy with ACNU and radiation significantly improved survival time as compared with protocol (C) (p<0.01). Malignant gliomas treated with protocol (A) had 40.5 months mean survival time (MST) and (B) had 25.7 months MST. On the other hand (C) group had a MST of 11.3 months (A:B, not significant, A:C p=0.00, B:C p=0.0002). Several important prognostic factors were identified. Histological type, initial performance status and operative resections were significant factors but ACNU total dosage, administration route and OK-432 had no influence on the survival after surgery. Nausea and vomiting were noticed immediately after ACNU administration, and later myelosuppression occurred in 25-29% of the patients. No relationship was observed between toxicity, and the single dosage of ACNU or administration routes.
