The development of dasatinib as a treatment for chronic myeloid leukemia (CML): from initial studies to application in newly diagnosed patients.

Abstract

PURPOSE:

Dasatinib is a dual Abl/Src tyrosine kinase inhibitor (TKI) designed as a prototypic short-acting BCR-ABL-targeted TKI that inhibits BCR-ABL with greater potency compared with imatinib, nilotinib, bosutinib, and ponatinib and has been shown to have potential immunomodulatory effects. Dasatinib is approved for the treatment of all phases of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia resistant or intolerant to prior imatinib treatment and first-line treatment for CML in chronic phase. In this article, the development of dasatinib as a treatment for patients with CML is reviewed.

METHODS:

This is a review of the relevant literature regarding dasatinib development in CML (2003-2013).

RESULTS:

Dasatinib demonstrates efficacy against most BCR-ABL mutations arising during imatinib therapy and is effective in treating patients with imatinib resistance due to other mechanisms. Randomized trial data show that first-line dasatinib provides superior responses compared with imatinib and enables patients to achieve early, deep responses correlated with improved longer-term outcomes. Dasatinib has a generally acceptable safety profile, with most adverse events (AEs) proving manageable and reversible. Cytopenias are commonly observed with dasatinib, and some nonhematologic AEs including pleural effusion have been consistently reported.

CONCLUSION:

Dasatinib is an effective treatment option for patients with CML.

• Authors: Andreas Hochhaus, Hagop Kantarjian
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 139 Issue 12 Pg. 1971-84 (Dec 2013) ISSN: 1432-1335 [Electronic] Germany
• PMID: 23942795 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antineoplastic Agents
• Protein Kinase Inhibitors
• Pyrimidines
• Thiazoles
• Fusion Proteins, bcr-abl
• Dasatinib

Topics

• Antineoplastic Agents (therapeutic use)
• Dasatinib
• Fusion Proteins, bcr-abl (genetics)
• Humans
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (drug therapy, genetics)
• Mutation
• Neoadjuvant Therapy (methods)
• Protein Kinase Inhibitors (therapeutic use)
• Pyrimidines (therapeutic use)
• Randomized Controlled Trials as Topic
• Thiazoles (therapeutic use)