Salvage therapy with temozolomide for recurrent or progressive high-grade gliomas refractory to ACNU [1-(4-amino-2-methyl-5-pyrimidynyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride

Abstract

This study aimed to determine safety, response rate, toxicity and 6-month progression-free survival (PFS) by using temozolomide (TMZ) as salvage chemotherapy for 25 adults with recurrent or progressive high-grade gliomas (HGGs) who failed 1-(4-amino-2-methyl-5-pyrimidynyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) therapy. Twenty-six patients with recurrent or progressive ACNU refractory HGG, including 12 with glioblastoma (GBM) and 13 with anaplastic astrocytoma (AA) were evaluated in a prospective study of temozolomide salvage chemotherapy. Following maximal surgical resection, the patients received 2-4 cycles of procarbazine (100 mg/m2, days 1-5), ACNU (80 mg/m2/d1, day 5) and, on days 5 and 12, cepharantine (70 mg) and vincristine (1.4 mg/m2). TMZ (150-200 mg/m2/d, days 1-5) was also administered every 28 days for ≤24 cycles. The six-month PFS was 50% (mean 10 months; 95% CI, 7-14 months) in 12 GBM patients and 39% (mean 17 months; 95% CI, 7-28 months) in 13 patients with AA. The best response to chemotherapy had no impact on the duration of disease control. Treatment-related toxicities included infections, while two (8%) patients developed neutropenia. In conclusion, TMZ can benefit patients with ACNU refractory HGG.