Cellular ara-CTP pharmacokinetics, response, and karyotype in newly diagnosed acute myelogenous leukemia.
We evaluated relationships between ara-CTP pharmacokinetics in myeloblasts, response, and karyotype in 147 patients with newly diagnosed AML treated on three protocols each initiated by a 3 g/m2 ara-C dose given over 2 h. Area under the curve of ara-CTP concentration times time (AUC) or peak ara-CTP concentration after this dose did not predict response or response duration, suggesting that inability to form ara-CTP is an unlikely mechanism of ara-C resistance. Following high-dose bolus ara-C therapy patients with INV [16] or del [16q] had long remissions despite low AUC and peak values while patients with -5, del [5q], -7, or del [7q] were frequently resistant despite average AUC and peak values. In 55 patients treated with high-dose continuous infusion ara-C as a single agent, steady-state ara-CTP concentrations were significantly lower in resistant patients (who again were disproportionately those with -5, del [5q], -7, or del [7q]) although there was no correlation with CR duration.
Estey
E H
EH
Department of Hematology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Keating
M J
MJ
McCredie
K B
KB
Freireich
E J
EJ
Plunkett
W
W
D000677:Amsacrine / Q000008:administration & dosage; D001085:Arabinofuranosylcytosine Triphosphate / Q000493:pharmacokinetics*; D001088:Arabinonucleotides / Q000493:pharmacokinetics*; D002872:Chromosome Deletion; D007446:Chromosome Inversion; D003561:Cytarabine / Q000008:administration & dosage / Q000627:therapeutic use*; D004351:Drug Resistance; D006801:Humans; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism
D001088:Arabinonucleotides; D000677:Amsacrine; D003561:Cytarabine; D001085:Arabinofuranosylcytosine Triphosphate