Evaluation of the L-stereoisomeric nucleoside analog troxacitabine for the treatment of acute myeloid leukemia.
Troxacitabine (BCH-4556; [-]-2'-deoxy-3'-oxacytidine) is a synthetic dioxolane that represents the first nucleoside analog with an L-isomer configuration to have shown important cytotoxic activity. Troxacitabine was obtained by exchanging the sulfur endocyclic atom with oxygen in the structure of lamivudine (3TC). Its unnatural stereochemistry renders it insensitive to some mechanisms of resistance of tumor cells to D-nucleosides, such as deamination by deoxycytidine deaminase and decreased active uptake by nucleoside transporters. These characteristics make troxacitabine a suitable alternative for patients with acute myelogenous leukemia as a potential way for overcoming resistance to ara-C therapy, which is the mainstay of acute myelogenous leukemia therapy at present. Clinically significant activity has been reported in Phase I studies in patients with advanced hematologic malignancies and has prompted troxacitabine to enter a series of Phase II trials in patients with refractory and relapsed acute myelogenous leukemia.
Quintás-Cardama
Alfonso
A
University of Texas MD Anderson Cancer Center, Department of Leukemia, Houston, TX 77030, USA.
Cortes
Jorge
J
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D003596:Cytosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D004148:Dioxolanes / Q000737:chemistry / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000188:drug therapy*; D009705:Nucleosides / Q000737:chemistry / Q000627:therapeutic use; D013237:Stereoisomerism
D000970:Antineoplastic Agents; D004148:Dioxolanes; D009705:Nucleosides; C074908:troxacitabine; D003596:Cytosine