Combination of 6-thioguanine, capecitabine, and celecoxib with temozolomide or lomustine for recurrent high-grade glioma.

Abstract

2057 Background: There is currently no standardized therapy for high-grade gliomas after recurrence. Since chemotherapy for these tumors is still dominated by alkylating agents, we evaluated the efficacy of combination chemotherapy with temozolomide (TMZ) or lomustine (CCNU) and 6-thioguanine (6-TG), capecitabine (CAP), and celecoxib (CEL). Methods: Forty-three patients with recurrent glioblastoma (GBM) 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-TG, CAP, and CEL. Endpoints were 12-month progression-free survival (PFS) for patients with AG and 6-month PFS for patients with GBM, duration of PFS, and MRI- based objective response rates (OR). Results: Results from the TMZ and CCNU treatment arms were combined in the final analysis because there was no statistically significant difference between them. 38 patients with GBM were treated with the CCNU-based regimen, and 5 received the TMZ-based regimen. For the 43 GBM patients, the OR rate was 12% and 33% had stable disease. For GBM, the 6 month PFS was 14% and median overall survival 32 weeks. For the 31 AG patients, the combined OR rate was 26% and 42% had stable disease; the 12 month PFS was 44%. Treatment was reasonably well tolerated; hematologic toxicity was most common and more frequent with CCNU. Conclusions: The combination therapy with 6-TG, CAP, and CEL plus either CCNU or TMZ does not appear to be more effective than conventional alkylating agents for patients with recurrent GBM. The combination, however, is promising for patients with recurrent AG. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer, Castle Biosciences, Genentech, Merck, Novartis, Pfizer, Schering-Plough Bayer, IMEDEX, Merck, Novartis, Schering-Plough Castle Biosciences, Celgene, Genentech, Lilly, MGI Pharma, Novartis, Pfizer, Schering-Plough Schering-Plough