Adaptive randomized study of idarubicin and cytarabine versus troxacitabine and cytarabine versus troxacitabine and idarubicin in untreated patients 50 years or older with adverse karyotype acute myeloid leukemia.
OBJECTIVE
Troxacitabine has activity in refractory myeloid leukemia, either as a single agent or when combined with cytarabine (ara-C) or with idarubicin. A prospective, randomized study was conducted in patients aged 50 years or older with untreated, adverse karyotype, acute myeloid leukemia (AML) to assess troxacitabine-based regimes as induction therapy.


METHODS
Patients were randomized to receive idarubicin and ara-C (IA) versus troxacitabine and ara-C (TA) versus troxacitabine and idarubicin (TI). A Bayesian design was used to adaptively randomly assign patients to treatment. Thus, although there was initially an equal chance for randomization to IA, TA, or TI, treatment arms with a higher success rate progressively received a greater proportion of patients.


RESULTS
Thirty-four patients were treated. Randomization to TI stopped after five patients and randomization to TA stopped after 11 patients. Defining success as complete remission (CR) that occurred within 49 days of starting treatment, success rates were 55% (10 of 18 patients) with IA, 27% (three of 11 patients) with TA, and 0% (zero of five patients) with TI. Because three CRs occurred after day 49, final CR rates were 55% (10 of 18 patients) with IA, 45% (five of 11 patients) with TA, and 20% (one of five patients) with TI. The probability that TA was inferior to IA was 70%, with a 5% probability that TA would have a 20% higher CR rate than IA. Survival was equivalent with all three regimens.


CONCLUSIONS
Neither troxacitabine combination was superior to IA in elderly patients with previously untreated adverse karyotype AML.
Department of Leukemia, Box 428, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA. frankgiles@aol.com
Francis J
FJ
Giles
Hagop M
HM
Kantarjian
Jorge E
JE
Cortes
Guillermo
G
Garcia-Manero
Srdan
S
Verstovsek
Stefan
S
Faderl
Deborah A
DA
Thomas
Alessandra
A
Ferrajoli
Susan
S
O'Brien
Jay K
JK
Wathen
Lian-Chun
LC
Xiao
Donald A
DA
Berry
Elihu H
EH
Estey
D000208:Acute Disease; D000367:Age Factors; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage; D003596:Cytosine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D004148:Dioxolanes / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D007262:Infusions, Intravenous; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D013534:Survival; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D004148:Dioxolanes; D003561:Cytarabine; C074908:troxacitabine; D003596:Cytosine; D015255:Idarubicin