TY - JOUR
T1 - Cellular ara-CTP pharmacokinetics, response, and karyotype in newly diagnosed acute myelogenous leukemia
AU - Estey, Elihu H.
AU - Keating, Michael J.
AU - McCredie, Kenneth B.
AU - Freireich, Emil J.
AU - Plunkett, William
PY - 1990/2
Y1 - 1990/2
N2 - 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 araC 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 araCTP 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.
AB - 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 araC 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 araCTP 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.
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M3 - Article
C2 - 2304361
AN - SCOPUS:0025008675
SN - 0887-6924
VL - 4
SP - 95
EP - 99
JO - Leukemia
JF - Leukemia
IS - 2
ER -