High-dose cytarabine in acute leukemia: toxicity and pharmacokinetics.
High-dose cytarabine (HDARA-C) at doses ranging from 1000 to 3000 mg/m2 administered as 30-min iv infusions was used in 12 patients with acute leukemia. HDARA-C toxicity was marked by nausea, vomiting, and somnolence; fever occurred in one patient. Myelosuppression was brief and reversible; the wbc count nadir occurred between Days 10 and 15 after treatment. In this study of a limited number of patients, no reliable conclusions could be drawn about antileukemic activity. However, (a) HDARA-C appeared to be a well-tolerated regimen in acute myeloblastic leukemia in complete remission; (b) a clear improvement was obtained in a patient with central nervous system leukemia; and (c) a sharp but transient decrease in peripheral blast cell counts was seen in two patients with acute myeloblastic leukemia. Cytarabine distribution was bi- or tri-compartmental; plasma final half-life was greater than 4 hrs in six patients. Pharmacokinetic parameters were not correlated with serum deoxycytidine deaminase activity. HDARA-C crosses the blood-brain barrier and may be useful in the prophylaxis against and treatment of central nervous system leukemia.
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D003561:Cytarabine / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism; D003564:Cytidine Deaminase; D005260:Female; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009700:Nucleoside Deaminases / Q000097:blood; D014839:Vomiting / Q000139:chemically induced
D003561:Cytarabine; D009700:Nucleoside Deaminases; D003564:Cytidine Deaminase; C011530:deoxycytidine deaminase