Phase II study of DTIC, ACNU, and vincristine combination chemotherapy for supratentorial malignant astrocytomas

This phase II clinical study evaluated the use of 5-(3-3'-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC) pretreatment to reduce cellular resistance and enhance the antitumor effects of chloroethyl nitrosoureas in 32 patients with supratentorial malignant gliomas, including 13 anaplastic astrocytoma and 19 glioblastoma multiforme. All patients received a total dose of 50-65 Gy radiation therapy after surgery. Chemotherapy consisted of DTIC (1 mg/kg) on days 1-5, 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (2 mg/kg) on day 5, and vincristine (0.02 mg/kg) on days 1 and 15 every 5 weeks. One patient achieved complete response and 12 patients showed partial response. Median survival time was 18 months and median time-to-progression was 11 months. No significant toxicity was encountered. There was no significant benefit of this pretreatment to combination chemotherapy when compared with previous results. This study does not support a further role for DTIC as a depleter of O6-alkylguanine deoxyribonucleic acid alkyltransferase activity preceding chloroethyl nitrosourea-based chemotherapy.