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A phase I trial of protracted oral fixed‐dose temozolomide
Author(s) -
Jones Suzanne F.,
Greco F. Anthony,
Gian Victor G.,
Miranda Fernando T.,
Raefsky Eric L.,
Hainsworth John D.,
Willcutt Noel T.,
Beschorner Aurelia F.,
Kennerly Glyndon,
Burris Howard A.
Publication year - 2005
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.21408
Subject(s) - temozolomide , medicine , nausea , regimen , toxicity , chemotherapy , phases of clinical research , anesthesia , surgery , urology , pharmacology
BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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 O 6 ‐methylguanine‐DNA methyltransferase. Cancer 2005. © 2005 American Cancer Society.