Intensively timed combination chemotherapy for the induction of adult patients with acute myeloid leukemia: long-term follow-up of a phase 2 study.
BACKGROUND
Despite advances in therapy, the majority of adult patients diagnosed with acute myeloid leukemia (AML) develop disease recurrence and die of their disease. Early intensification of treatment for AML using timed sequential therapy (TST) has been proposed as a means of improving the survival outcome in children. The Children's Cancer Group demonstrated that children with AML who were randomized to receive 2 courses of daunorubicin, cytarabine, thioguanine, etoposide, and dexamethasone (the DCTER regimen) given 10 days apart had an improved event-free survival (EFS) and disease-free survival (DFS) (42% ± 7% and 55% ± 9%, respectively, at 2 years). Reports have suggested an improved outcome in adult patients with AML using TST (at the cost of increased toxicity). The current study was conducted to evaluate the feasibility and effectiveness of the intensively timed DCTER regimen for non-core-binding factor AML in adult patients aged <50 years.


METHODS
Between February 2004 and August 2005, 61 patients received this timed sequential induction regimen. Their outcomes were compared with matched historical patients treated with the combination of idarubicin and cytarabine (IA).


RESULTS
The median follow-up for surviving patients was 67 months (range, 35-85 months). The timed sequential DCTER regimen had a lower complete remission (CR) rate when compared with the IA combination,, (71% vs 80%, respectively), but this appeared to be counterbalanced by a higher long-term leukemia-free survival rate using the intensified regimen (48% vs 30%, respectively) in patients who achieved a CR (P = .06).


CONCLUSIONS
The intensively timed regimen of DCTER was found to induce durable remissions in adult patients with AML, including those patients with high-risk disease. The identification of patients who would potentially benefit from such an intensive regimen may justify the higher early risk of early treatment failure that was found to accompany the intensified DCTER regimen in selected patients.
Rytting
Michael
M
Department of Pediatrics, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA. mrytting@mdanderson.org
Ravandi
Farhad
F
Estey
Elihu
E
Cortes
Jorge
J
Faderl
Stefan
S
Garcia-Manero
Guillermo
G
Jeha
Sima
S
Ouzounian
Souzanne
S
Pierce
Sherry
S
Kantarjian
Hagop
H
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D003630:Daunorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D013866:Thioguanine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use
D003561:Cytarabine; D005047:Etoposide; D003907:Dexamethasone; D013866:Thioguanine; D003630:Daunorubicin