Treatment of childhood acute myelogenous leukemia with an intensive regimen (AML-87) that individualizes etoposide and cytarabine dosages: short- and long-term effects.
The purpose of this study was to assess the feasibility and efficacy of a treatment regimen for pediatric acute myelogenous leukemia (AML) that uses four rotating drug pairs and adjusts dosages of etoposide and cytarabine to target specific plasma concentrations. Thirty-one girls and 27 boys (median age, 9.7 years) with de novo AML were treated on the protocol. Six cycles of chemotherapy were planned. Cycles 1 to 4 comprised the drug combinations cytarabine plus etoposide, cytarabine plus daunomycin, etoposide plus amsacrine, and etoposide plus azacitidine, respectively. For cycles 5 and 6, the first two combinations were repeated. Dosages were adjusted to achieve plasma concentrations of 1.0 microM +/- 0.1 microM cytarabine and 30 microM +/- 0.3 microM etoposide. Forty-four patients (76%) entered complete remission. Of those, 24 have had relapses; 23 remain alive in first or subsequent remission. The 5-year event-free survival (EFS) estimate was 31.0% +/- 5.9%; the 5-year survival estimate was 41.4% +/- 6.3%. Six patients (10%) died of the toxic effects of therapy. Severe neutropenia occurred in all cycles. Long-term complications of therapy included hepatitis C, cardiac insufficiency, and hearing loss. Adjustment of cytarabine and etoposide dosage was feasible for achieving targeted plasma drug concentrations; however, the potential clinical efficacy of this approach was offset by substantial acute and long-term toxicity.
Arnaout
M K
MK
Department of Hematology-Oncology, St Jude Children's Research Hospital, Memphis, TN 38105-2794, USA.
Radomski
K M
KM
Srivastava
D K
DK
Tong
X
X
Belt
J R
JR
Raimondi
S C
SC
Behm
F G
FG
Santana
V M
VM
Crom
W R
WR
Mirro
J
J
Ribeiro
R C
RC
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000008:administration & dosage / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000008:administration & dosage / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D016896:Treatment Outcome
D003561:Cytarabine; D005047:Etoposide