Cellular ara-CTP pharmacokinetics, response, and karyotype in newly diagnosed acute myelogenous leukemia.

Abstract

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.

• Authors: E H Estey, M J Keating, K B McCredie, E J Freireich, W Plunkett
• Journal: Leukemia (Leukemia) Vol. 4 Issue 2 Pg. 95-9 (Feb 1990) ISSN: 0887-6924 [Print] England
• PMID: 2304361 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Arabinonucleotides
• Amsacrine
• Cytarabine
• Arabinofuranosylcytosine Triphosphate

Topics

• Amsacrine (administration & dosage)
• Arabinofuranosylcytosine Triphosphate (pharmacokinetics)
• Arabinonucleotides (pharmacokinetics)
• Chromosome Deletion
• Chromosome Inversion
• Cytarabine (administration & dosage, therapeutic use)
• Drug Resistance
• Humans
• Karyotyping
• Leukemia, Myeloid, Acute (drug therapy, genetics, metabolism)