Variables predicting response to high dose cytosine arabinoside therapy in patients with refractory acute leukemia.
The cytotoxic effect of cytosine arabinoside (ara-C) is presumably mediated by cytosine arabinoside 5'-triphosphate (ara-CTP). We tested for a correlation between intracellular ara-CTP pharmacokinetics and clinical response among 51 patients who received high dose ara-C (3 g/m2 at 12-hr intervals) as therapy for refractory acute leukemia. After accounting for pretreatment clinical variables that correlated with response, measurement of ara-CTP pharmacokinetics added significant prognostic information. This provides a rationale for manipulation of schedules of high dose ara-C administration in those patients whose pharmacokinetic characteristics are inconsistent with response to an every 12-hr schedule.
Estey
E
E
Department of Hematology, University of Texas M.D. Anderson Hospital and Tumor Institute, Houston 77030.
Plunkett
W
W
Dixon
D
D
Keating
M
M
McCredie
K
K
Freireich
E J
EJ
D000208:Acute Disease; D003561:Cytarabine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007938:Leukemia / Q000188:drug therapy*
D003561:Cytarabine