The correlation of response with plasma pharmacokinetics and polyamine concentrations in patients with acute myelogenous leukemia receiving amonafide.
We have investigated the correlation of clinical responses (decreases of white blood cells and peripheral blasts) with pharmacokinetic and pharmacodynamic parameters in patients with acute myelogenous leukemia who are receiving amonafide. The increase of plasma polyamine concentrations was used as a measure of tumor sensitivity (pharmacodynamic effect). The correlations between pharmacokinetic parameters (biological half life, area under the concentration time curve (AUC), total plasma clearance), decreases of total white blood cells and peripheral leukemic blasts were weak (maximum r = 0.47). Correlations of response with polyamines were better than those with pharmacokinetic parameters, but not exceptional; of these, the best correlations were with the increase of putrescine. On the other hand, correlations of combinations of AUC and increases of plasma polyamine concentrations with decreases of total white blood cell counts approached unity. Unexpectedly, decreases of peripheral leukemic blasts were correlated just as well with putrescine increase alone (r = 0.91, P = 0.003) or with a combination of polyamine increases and AUC (r = 0.92, P = 0.036).
Benvenuto
J A
JA
Department of Clinical Investigation, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Johnston
D A
DA
Nishioka
K
K
D000225:Adenine; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D006801:Humans; D007094:Imides; D007546:Isoquinolines / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D015470:Leukemia, Myeloid, Acute / Q000097:blood* / Q000188:drug therapy; D007958:Leukocyte Count / Q000187:drug effects; D008657:Metabolic Clearance Rate; D053644:Naphthalimides; D063065:Organophosphonates; D011073:Polyamines / Q000097:blood*; D012044:Regression Analysis; D013997:Time Factors
D000970:Antineoplastic Agents; D007094:Imides; D007546:Isoquinolines; D053644:Naphthalimides; D063065:Organophosphonates; D011073:Polyamines; C037020:amonafide; D000225:Adenine