COMBINATION OF 6-THIOGUANINE, PROCARBAZINE, LOMUSTINE, AND HYDROXYUREA FOR PATIENTS WITH RECURRENT MALIGNANT GLIOMAS

OBJECTIVE: To determine the efficacy of the combination of 6-thioguani ne, procarbazine, lomustine, and hydroxyurea for patients with recurre nt malignant gliomas after failure of either previous radiotherapy alo ne or previous radiotherapy plus nitrosourea-based chemotherapy. METHO DS: Seventy-seven patients with recurrent malignant gliomas were studi ed. 6-Thioguanine was administered for 4 days before lomustine, and pr ocarbazine was administered for 1 day before and 2 days after lomustin e to potentiate lomustine's antitumor effect. Hydroxyurea was initiate d 1 day before lomustine and continued for a total of 3 days. RESULTS: Thirty patients with glioblastomas and 47 patients with anaplastic gl iomas were eligible for evaluation. In the glioblastoma group, 2 of 30 patients had a partial response and 8 of 30 patients had stable disea se. This group of patients who responded and had stable disease includ ed 6 of 10 patients who had not undergone previous chemotherapy but on ly 4 of 20 who had undergone previous chemotherapy. The overall median time to disease progression for the glioblastoma group was 9 weeks. I n the anaplastic glioma group, 11 of 47 patients had a partial respons e and 25 of 47 had stable disease, including 23 of 30 without previous chemotherapy and 13 of 17 who had undergone previous chemotherapy. Th e median time to disease progression for the whole anaplastic glioma g roup was 24 weeks; however, the time to disease progression was 50 wee ks for responding patients who had not undergone previous chemotherapy and 25 weeks for those who had undergone previous chemotherapy. CONCL USION: Our results indicate that chemotherapy with a combination of 6- thioguanine, procarbazine, lomustine, and hydroxyurea is active for pa tients with recurrent anaplastic gliomas and glioblastomas not previou sly treated with nitrosourea-based chemotherapy but is inactive for pa tients with glioblastomas previously treated with chemotherapy.