Efficacy and safety of dasatinib in imatinib-resistant or -intolerant patients with chronic myeloid leukemia in blast phase.

Abstract

Dasatinib is an inhibitor of BCR-ABL and SRC-family kinases for patients with imatinib-resistant or -intolerant chronic myelogenous leukemia (CML). In this international phase II trial, dasatinib was administered orally (70 mg twice daily) to patients with myeloid blast phase (MBP, n=109) or lymphoid blast phase (LBP, n=48) CML. After a minimum follow-up of 12 months (range 0.03-20.7 months), major hematologic responses were induced in 34% (MBP-CML) and 35% (LBP-CML) of patients. Major cytogenetic responses were attained in 33% (MBP-CML) and 52% (LBP-CML) of patients and complete cytogenetic responses were attained in 26 and 46%, respectively. Median progression-free survival was 6.7 (MBP-CML) and 3.0 (LBP-CML) months. Median overall survival was 11.8 (MBP-CML) and 5.3 (LBP-CML) months. Overall, dasatinib had acceptable tolerability. Fluid retention events were more frequent in the MBP-CML than the LBP-CML cohort: pleural effusion occurred in 36 and 13% (all grades) and 15 and 6% (grades 3/4), respectively. Other non-hematologic side effects were primarily grade 1/2; grade 3/4 events were recorded in <or=6% of patients, except febrile neutropenia (15%). Cytopenias were noted in the majority of patients, and were manageable with dose interruptions/reductions. Dasatinib is associated with a promising rate of response in this high-risk population.

• Authors: J Cortes, D-W Kim, E Raffoux, G Martinelli, E Ritchie, L Roy, S Coutre, S Corm, N Hamerschlak, J-L Tang, A Hochhaus, H J Khoury, T H Brümmendorf, M Michallet, G Rege-Cambrin, C Gambacorti-Passerini, J P Radich, T Ernst, C Zhu, J M A Van Tornout, M Talpaz
• Journal: Leukemia (Leukemia) Vol. 22 Issue 12 Pg. 2176-83 (Dec 2008) ISSN: 1476-5551 [Electronic] England
• PMID: 18754032 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Benzamides
• Piperazines
• Protein Kinase Inhibitors
• Pyrimidines
• Thiazoles
• Imatinib Mesylate
• Dasatinib

Topics

• Administration, Oral
• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents
• Benzamides
• Blast Crisis (drug therapy)
• Combined Modality Therapy
• Dasatinib
• Disease-Free Survival
• Drug Resistance, Neoplasm
• Female
• Genes, abl (genetics)
• Hematopoietic Stem Cell Transplantation
• Humans
• Imatinib Mesylate
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (drug therapy, genetics, pathology)
• Male
• Middle Aged
• Piperazines
• Protein Kinase Inhibitors (administration & dosage, adverse effects)
• Pyrimidines (administration & dosage, adverse effects)
• Thiazoles (administration & dosage, adverse effects)
• Treatment Outcome
• Young Adult