We evaluated the efficacy of
temozolomide (TMZ) or
lomustine (
CCNU) in combination with
6-thioguanine,
capecitabine, and
celecoxib for the treatment of recurrent high-grade
glioma. Forty-three patients with recurrent
glioblastoma and 31 patients with recurrent anaplastic
glioma (AG) were enrolled in this open-label, non-comparative study. Patients previously treated with TMZ received
CCNU while all others received TMZ; all patients received
6-thioguanine,
capecitabine, and
celecoxib. Endpoints were 12-month progression-free survival (PFS) for patients with AG, 6-month PFS for patients with
glioblastoma, duration of PFS, and MRI-based objective response rates. Results from the TMZ and
CCNU treatment arms were combined in the final analysis because there was no statistically significant difference between them. Thirty-eight patients with
glioblastoma were treated with the
lomustine-based regimen, and five received the TMZ-based regimen. For the 43
glioblastoma patients, the objective response rate was 12 and 33% had stable disease; the 6-month PFS was 14% and median overall survival 32 weeks. For the 31 AG patients, the combined objective response rate was 26 and 42% had stable disease; the 12 month PFS was 44%. Treatment was reasonably well tolerated with hematological toxicity common and more frequent with
CCNU than TMZ. The combination
therapy with
6-thioguanine,
capecitabine and
celecoxib plus
CCNU or TMZ does not appear to be more effective than other
alkylating agent schedules for patients with recurrent
glioblastoma. The combination, however, is promising for patients with recurrent high-grade AG.