Interim comparison of a continuous infusion versus a short daily infusion of cytarabine given in combination with cladribine for pediatric acute myeloid leukemia.
OBJECTIVE
To identify the optimal schedule for infusion of cytarabine (ara-C) given with cladribine (2-CdA) to pediatric patients with acute myeloid leukemia (AML), and to compare the effects of the two schedules on the pharmacokinetics of ara-C triphosphate (ara-CTP) in leukemic cells.


METHODS
Forty-nine pediatric patients with newly diagnosed primary AML received a 5-day course of ara-C 500 mg/m(2)/d and 2-CdA 9 mg/m(2)/d. They were randomly assigned to receive ara-C as either a 2-hour daily infusion (arm A) or a continuous infusion (arm B). Cellular pharmacokinetics were studied on days 1 and 2. All patients then received two courses of remission induction chemotherapy with daunorubicin, ara-C, and etoposide (DAV).


RESULTS
Thirty-two percent of patients (seven of 22) in arm A and 63% (17 of 27) in arm B entered complete remission (P =.045) after ara-C and 2-CdA therapy. Coadministration of 2-CdA increased the intracellular concentration of ara-CTP in 20 of 36 patients, although we found no statistically significant difference between the treatment arms in this effect (P =.63). The incidence of toxicity did not differ significantly between the two treatment arms (P =.53). After two courses of DAV, the rate of complete remission was 91% in arm A and 96% in arm B (P =.58).


CONCLUSIONS
Intracellular accumulation of ara-CTP is increased when 2-CdA is given with ara-C, but no schedule-dependent differences in this effect were seen. The combination of 2-CdA and ara-C seems to be effective therapy for pediatric AML.
Crews
Kristine R
KR
Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, TN 38105, USA. kristine.rews@stjude.org
Gandhi
Varsha
V
Srivastava
Deo Kumar
DK
Razzouk
Bassem I
BI
Tong
Xin
X
Behm
Fred G
FG
Plunkett
William
W
Raimondi
Susana C
SC
Pui
Ching-Hon
CH
Rubnitz
Jeffrey E
JE
Stewart
Clinton F
CF
Ribeiro
Raul C
RC
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001085:Arabinofuranosylcytosine Triphosphate / Q000378:metabolism; D001853:Bone Marrow / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D017338:Cladribine / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003630:Daunorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D012074:Remission Induction
D003561:Cytarabine; D001085:Arabinofuranosylcytosine Triphosphate; D017338:Cladribine; D005047:Etoposide; D003630:Daunorubicin