Therapy of refractory or recurrent childhood acute myeloid leukemia using amsacrine and etoposide with or without azacitidine: a Pediatric Oncology Group randomized phase II study.
OBJECTIVE
A randomized study compared the combination of amsacrine (100 mg/m2/d on days 1 to 5) and etoposide (200 mg/m2/d on days 1 to 3) with the same two agents plus azacitidine (250 mg/m2/d on days 4 to 50) for the therapy of induction-resistant or relapse childhood acute myeloid leukemia (AML).


METHODS
One hundred sixty-seven assessable children with AML who either had failed to respond to primary induction therapy (group 1, n = 41) or had relapsed (group 2, n = 126) were randomized.


RESULTS
Overall, there were 56 complete responses (34%; SE 4%). Among primary refractory patients (group 1), the complete response rate was higher with the three-drug regimen (18% vs 53%, P = .03). In the relapsed patients (group 2), there was no difference in complete response rates related to treatment (31% vs 35%, P = .3). There were 17 early deaths. The major toxicities for both regimens were myelosuppression and infection.


CONCLUSIONS
The overall complete response rate of 34% in this patient population is indicative of effective antileukemic activity. For patients with relapsed leukemia, the addition of azacitidine to etoposide and amsacrine did not improve response. The suggested advantage of the three-drug regimen for induction failures warrants further investigation.
Steuber
C P
CP
Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Krischer
J
J
Holbrook
T
T
Camitta
B
B
Land
V
V
Sexauer
C
C
Mahoney
D
D
Weinstein
H
H
D000293:Adolescent; D000328:Adult; D000677:Amsacrine / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001374:Azacitidine / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*
D000677:Amsacrine; D005047:Etoposide; D001374:Azacitidine