Phase I Study of Continuous Infusion Schedule of (E)-2'-Deoxy-2'-(Fluoromethylene) Cytidine (Tezacitabine, FMdC) in Hematologic Malignancies
Patients with leukemias that have relapsed from previous therapies have a low cure rate.
Hence the need to discover new antileukemic agents. Tezacitabine is a nucleoside analogue
with equivalent or even superior activity when compared with ara-C in leukemic cell lines.
It has shown significant antitumor activity in vitro and in vivo tumor models. Several phase
I studies with various dosing schedules have been conducted in solid tumors where the
dose-limiting toxicity (DLT) is mainly myelosuppression, usually a favorable feature for
development of leukemia. In a phase I study in hematological malignancies, we used
Tezacitabine as a bolus infusion daily x 5. The DLT consisted of grade 3 CNS toxicities and
mucositis in 3/6 patients. The study is ongoing and we are currently evaluating a dose level
of 7.5 mg/m2 as possible Maximum Tolerated Dose (MTD). However, in view of the fact that
tezacitabine is a cell cycle specific agent with a short terminal plasma half-life of 2 to 6
hours, a continuous infusion dosing schedule may enhance the activity and reduce the
incidence of adverse effects of tezacitabine.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose (MTD)
MTD determination made from dose level without a dose-limiting toxicity (DLT)
Stefan Faderl, MD
UT MD Anderson Cancer Center
United States: Food and Drug Administration
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