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A phase I trial of protracted oral fixed-dose temozolomide†
Article first published online: 30 AUG 2005
Copyright © 2005 American Cancer Society
Volume 104, Issue 9, pages 1985–1991, 1 November 2005
How to Cite
Jones, S. F., Greco, F. A., Gian, V. G., Miranda, F. T., Raefsky, E. L., Hainsworth, J. D., Willcutt, N. T., Beschorner, A. F., Kennerly, G. and Burris, H. A. (2005), A phase I trial of protracted oral fixed-dose temozolomide. Cancer, 104: 1985–1991. doi: 10.1002/cncr.21408
Presented in part at the 37th Annual Meeting of the American Society of Clinical Oncology, San Francisco, California, May 12–15, 2001.
- Issue published online: 17 OCT 2005
- Article first published online: 30 AUG 2005
- Manuscript Accepted: 3 JUN 2005
- Manuscript Revised: 24 MAY 2005
- Manuscript Received: 7 FEB 2005
- Phase I;
- protracted administration;
- dose-limiting toxicity;
- solid tumor types
The current Phase I trial was conducted to determine the dose-limiting toxicity (DLT), maximum tolerated dose, and recommended Phase II dose of oral fixed-dose temozolomide when administered for 5 of every 7 days on a continuous basis.
Patients received a fixed dose of temozolomide daily for 5 of every 7 days continuously. Four weeks of treatment were considered 1 treatment cycle. Patients were accrued at 7 different dose levels ranging from 100 mg/day to 360 mg/day.
Forty-six patients received 111 cycles of therapy. DLT consisted of myelosuppression, particularly thrombocytopenia. The primary nonhematologic toxicities were nausea and emesis, which were easily controlled with antiemetics.
Protracted administration of temozolomide at a fixed dose of 300 mg/day for 5 of every 7 days continuously was well tolerated and allowed greater dose intensity compared with various other schedules. This regimen could potentially increase antitumor activity as protracted temozolomide schedules inhibit DNA repair by depletion of the repair protein O6-methylguanine-DNA methyltransferase. Cancer 2005. © 2005 American Cancer Society.