Intensively timed combination chemotherapy for the induction of adult patients with acute myeloid leukemia

Michael Rytting, Farhad Ravandi, Elihu Estey, Jorge Cortes, Stefan Faderl, Guillermo Garcia-Manero, Sima Jeha, Souzanne Ouzounian, Sherry Pierce, Hagop Kantarjian

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5272-5278
Number of pages7
JournalCancer
Volume116
Issue number22
DOIs
StatePublished - Nov 15 2010
Externally publishedYes

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Combination Drug Therapy
Acute Myeloid Leukemia
Cytarabine
Disease-Free Survival
Idarubicin
Thioguanine
Daunorubicin
Etoposide
Therapeutics
Treatment Failure
Dexamethasone
Leukemia
Survival Rate
Recurrence
Survival

Keywords

  • acute myeloid leukemia (AML)
  • intensively timed chemotherapy
  • outcome
  • remission

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Rytting, M., Ravandi, F., Estey, E., Cortes, J., Faderl, S., Garcia-Manero, G., ... Kantarjian, H. (2010). Intensively timed combination chemotherapy for the induction of adult patients with acute myeloid leukemia. Cancer, 116(22), 5272-5278. https://doi.org/10.1002/cncr.25516

Intensively timed combination chemotherapy for the induction of adult patients with acute myeloid leukemia. / Rytting, Michael; Ravandi, Farhad; Estey, Elihu; Cortes, Jorge; Faderl, Stefan; Garcia-Manero, Guillermo; Jeha, Sima; Ouzounian, Souzanne; Pierce, Sherry; Kantarjian, Hagop.

In: Cancer, Vol. 116, No. 22, 15.11.2010, p. 5272-5278.

Research output: Contribution to journalArticle

Rytting, M, Ravandi, F, Estey, E, Cortes, J, Faderl, S, Garcia-Manero, G, Jeha, S, Ouzounian, S, Pierce, S & Kantarjian, H 2010, 'Intensively timed combination chemotherapy for the induction of adult patients with acute myeloid leukemia', Cancer, vol. 116, no. 22, pp. 5272-5278. https://doi.org/10.1002/cncr.25516
Rytting, Michael ; Ravandi, Farhad ; Estey, Elihu ; Cortes, Jorge ; Faderl, Stefan ; Garcia-Manero, Guillermo ; Jeha, Sima ; Ouzounian, Souzanne ; Pierce, Sherry ; Kantarjian, Hagop. / Intensively timed combination chemotherapy for the induction of adult patients with acute myeloid leukemia. In: Cancer. 2010 ; Vol. 116, No. 22. pp. 5272-5278.
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abstract = "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.",
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AU - Garcia-Manero, Guillermo

AU - Jeha, Sima

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