Prospective, multicenter, phase II study on reducing the dosage of idarubicin and FLAG for patients younger than 65 years with resistant acute myeloid leukemia: a comparison with a higher dosage trial.

Abstract

We previously assessed continuous infusion (CI) of fludarabine and cytarabine plus idarubicin (CI-FLAG1) for patients under 65 years of age with resistant acute myeloid leukemia. Induction chemotherapy consisted of idarubicin (IDA) plus fludarabine and cytarabine (ARAC) as a 24-hour CI. In response to induction, 31.6% of patients achieved complete remission (CR) and in 68.4% the treatment failed. We concluded that CI-FLAG1 carried a high risk of toxicity and reduced CI-FLAG doses were recommended. Therefore, we revised the protocol (CI-FLAG2) by reducing the dose of IDA and ARAC. In total, 38 and 68 patients were enrolled into CI-FLAG1 and CI-FLAG2, respectively. When comparing outcomes between CI-FLAG1 and CI-FLAG2, there were no differences in terms of the CR rate (p = 0.306) and the overall response rate (ORR; p = 0.206). The treatment failure patterns were different between CI-FLAG1 and CI-FLAG2. The median overall survival showed only a trend towards longer survival in CI-FLAG2 (p = 0.074). Among intermediate-risk patients, there were high response rates favoring CI-FLAG2 in terms of the CR rate (p = 0.108), the ORR (p = 0.031), and overall survival (p = 0.033). This represented a relatively improved response rate compared to our previous study. There was decreased aplasia with dose reductions at the expense of increased resistance. A reduced dose of CI-FLAG might be most beneficial for intermediate-risk groups.

• Authors: Hawk Kim, Je-Hwan Lee, Young-Don Joo, Sung Hwa Bae, Jung-Hee Lee, Dae-Young Kim, Won-Sik Lee, Hun-Mo Ryoo, Jae-Cheol Jo, Jae-Hoo Park, Kyoo-Hyung Lee
• Journal: Acta haematologica (Acta Haematol) Vol. 132 Issue 1 Pg. 87-96 ( 2014) ISSN: 1421-9662 [Electronic] Switzerland
• PMID: 24513865 (Publication Type: Clinical Trial, Phase II, Comparative Study, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 S. Karger AG, Basel.

Chemical References

• Cytarabine
• Granulocyte Colony-Stimulating Factor
• Vidarabine
• Idarubicin

Topics

• Adolescent
• Adult
• Age Factors
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Cytarabine (administration & dosage)
• Dose-Response Relationship, Drug
• Drug Resistance, Neoplasm
• Female
• Granulocyte Colony-Stimulating Factor (administration & dosage)
• Hematopoietic Stem Cell Transplantation
• Humans
• Idarubicin (administration & dosage)
• Infusions, Intravenous
• Leukemia, Myeloid, Acute (drug therapy, therapy)
• Male
• Middle Aged
• Prospective Studies
• Recurrence
• Remission Induction
• Risk Factors
• Treatment Failure
• Treatment Outcome
• Vidarabine (administration & dosage, analogs & derivatives)
• Young Adult