Biomaterial Database

Dasatinib: from treatment of imatinib-resistant or -intolerant patients with chronic myeloid leukemia to treatment of patients with newly diagnosed chronic phase chronic myeloid leukemia. 2012

Brian L Abbott

Department of Medical Oncology, Sletten Cancer Institute, Great Falls, Montana 59405, USA.

BACKGROUND Imatinib is an effective treatment for patients with newly diagnosed chronic phase chronic myeloid leukemia (CML-CP), but resistance to imatinib can occur. Second-generation BCR-ABL inhibitors have shorter onset times and higher rates of complete cytogenetic response (CCyR) than imatinib. Dasatinib has a half-maximal inhibitory concentration 325 times lower than imatinib for BCR-ABL substrate phosphorylation in vitro and is less susceptible to most known molecular mechanisms of BCR-ABL imatinib resistance. OBJECTIVE This study summarized published data on the use of dasatinib in CML-CP, reviewed the importance of early response to therapy, and discussed additional therapies for patients with newly diagnosed disease. METHODS PubMed was searched through June 2011 for English-language publications with the following search terms: imatinib, dasatinib, nilotinib, chronic myeloid/myelogenous leukemia or CML, and clinical trial. To identify follow-up data from published trials and data on trials in progress and products in development, similar searches were conducted for abstract and clinical trial databases. Relevant articles and abstracts were identified as those reporting results of Phase II and III clinical trials, predictors of treatment response, and treatment guidelines. No prespecified inclusion or exclusion criteria were used. RESULTS Dasatinib was effective in patients resistant to imatinib and more effective than high-dose imatinib in patients with newly diagnosed CML who were resistant to standard dose imatinib. Compared with imatinib, dasatinib induced superior response rates and patient outcomes earlier in the disease. In a Phase III trial in patients with newly diagnosed CML-CP, dasatinib 100 mg once daily induced significantly higher and faster rates of confirmed CCyR and major molecular response by 12 months versus imatinib and was generally well tolerated. Early achievement of CCyR was associated with better long-term progression-free survival. Dasatinib was approved by the U.S. Food and Drug Administration and the European Medicines Agency for initial treatment of CML-CP. CONCLUSIONS Dasatinib was an effective treatment with the potential to improve long-term outcomes for patients with newly diagnosed CML-CP.

UI	MeSH Term	Description	Entries
D010879	Piperazines	Compounds that are derived from PIPERAZINE.
D011743	Pyrimidines	A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000068877	Imatinib Mesylate	A tyrosine kinase inhibitor and ANTINEOPLASTIC AGENT that inhibits the BCR-ABL kinase created by chromosome rearrangements in CHRONIC MYELOID LEUKEMIA and ACUTE LYMPHOBLASTIC LEUKEMIA, as well as PDG-derived tyrosine kinases that are overexpressed in gastrointestinal stromal tumors.	Alpha-(4-methyl-1-piperazinyl)-3'-((4-(3-pyridyl)-2-pyrimidinyl)amino)-p-tolu-p-toluidide,CGP 57148,CGP-57148,CGP57148B,Gleevec,Glivec,Imatinib,Imatinib Methanesulfonate,ST 1571,ST1571,STI 571,STI-571,STI571,CGP57148,Mesylate, Imatinib,Methanesulfonate, Imatinib
D000069439	Dasatinib	A pyrimidine and thiazole derived ANTINEOPLASTIC AGENT and PROTEIN KINASE INHIBITOR of BCR-ABL KINASE. It is used in the treatment of patients with CHRONIC MYELOID LEUKEMIA who are resistant or intolerant to IMATINIB.	(18F)-N-(2-chloro-6-methylphenyl)-2-(6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-ylamino)thiazole-5-carboxamide,BMS 354825,BMS-354825,BMS354825,N-(2-chloro-6-methylphenyl)-2-(6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-ylamino)thiazole-5-carboxamide,Sprycel,354825, BMS
D001549	Benzamides	BENZOIC ACID amides.
D013844	Thiazoles	Heterocyclic compounds where the ring system is composed of three CARBON atoms, a SULFUR and NITROGEN atoms.	Thiazole
D015464	Leukemia, Myelogenous, Chronic, BCR-ABL Positive	Clonal hematopoetic disorder caused by an acquired genetic defect in PLURIPOTENT STEM CELLS. It starts in MYELOID CELLS of the bone marrow, invades the blood and then other organs. The condition progresses from a stable, more indolent, chronic phase (LEUKEMIA, MYELOID, CHRONIC PHASE) lasting up to 7 years, to an advanced phase composed of an accelerated phase (LEUKEMIA, MYELOID, ACCELERATED PHASE) and BLAST CRISIS.	Granulocytic Leukemia, Chronic,Leukemia, Granulocytic, Chronic,Leukemia, Myelocytic, Chronic,Leukemia, Myelogenous, Chronic,Leukemia, Myeloid, Chronic,Myelocytic Leukemia, Chronic,Myelogenous Leukemia, Chronic,Myeloid Leukemia, Chronic,Leukemia, Chronic Myelogenous,Leukemia, Chronic Myeloid,Leukemia, Myelogenous, Ph1 Positive,Leukemia, Myelogenous, Ph1-Positive,Leukemia, Myeloid, Ph1 Positive,Leukemia, Myeloid, Ph1-Positive,Leukemia, Myeloid, Philadelphia Positive,Leukemia, Myeloid, Philadelphia-Positive,Myelogenous Leukemia, Ph1-Positive,Myeloid Leukemia, Ph1-Positive,Myeloid Leukemia, Philadelphia-Positive,Chronic Granulocytic Leukemia,Chronic Granulocytic Leukemias,Chronic Myelocytic Leukemia,Chronic Myelocytic Leukemias,Chronic Myelogenous Leukemia,Chronic Myelogenous Leukemias,Chronic Myeloid Leukemia,Chronic Myeloid Leukemias,Granulocytic Leukemias, Chronic,Leukemia, Chronic Granulocytic,Leukemia, Chronic Myelocytic,Leukemia, Ph1-Positive Myelogenous,Leukemia, Ph1-Positive Myeloid,Leukemia, Philadelphia-Positive Myeloid,Leukemias, Chronic Granulocytic,Leukemias, Chronic Myelocytic,Leukemias, Chronic Myelogenous,Leukemias, Chronic Myeloid,Leukemias, Ph1-Positive Myelogenous,Leukemias, Ph1-Positive Myeloid,Leukemias, Philadelphia-Positive Myeloid,Myelocytic Leukemias, Chronic,Myelogenous Leukemia, Ph1 Positive,Myelogenous Leukemias, Chronic,Myelogenous Leukemias, Ph1-Positive,Myeloid Leukemia, Ph1 Positive,Myeloid Leukemia, Philadelphia Positive,Myeloid Leukemias, Chronic,Myeloid Leukemias, Ph1-Positive,Myeloid Leukemias, Philadelphia-Positive,Ph1-Positive Myelogenous Leukemia,Ph1-Positive Myelogenous Leukemias,Ph1-Positive Myeloid Leukemia,Ph1-Positive Myeloid Leukemias,Philadelphia-Positive Myeloid Leukemia,Philadelphia-Positive Myeloid Leukemias
D015466	Leukemia, Myeloid, Chronic-Phase	The initial phase of chronic myeloid leukemia consisting of an relatively indolent period lasting from 4 to 7 years. Patients range from asymptomatic to those exhibiting ANEMIA; SPLENOMEGALY; and increased cell turnover. There are 5% or fewer blast cells in the blood and bone marrow in this phase.	Granulocytic Leukemia, Chronic, Stable-Phase,Leukemia, Granulocytic, Chronic-Phase,Leukemia, Myelogenous, Chronic-Phase,Leukemia, Myeloid, Stable-Phase,Myelogenous Leukemia, Chronic, Chronic-Phase,Myeloid Leukemia, Chronic, Chronic-Phase,Myeloid Leukemia, Chronic, Stable-Phase,Granulocytic Leukemia, Chronic, Stable Phase,Leukemia, Granulocytic, Chronic Phase,Leukemia, Myelogenous, Chronic Phase,Leukemia, Myeloid, Chronic Phase,Leukemia, Myeloid, Stable Phase,Myelogenous Leukemia, Chronic, Chronic Phase,Myeloid Leukemia, Chronic, Chronic Phase
D017326	Clinical Trials, Phase III as Topic	Works about comparative studies to verify the effectiveness of diagnostic, therapeutic, or prophylactic drugs, devices, or techniques determined in phase II studies. During these trials, patients are monitored closely by physicians to identify any adverse reactions from long-term use. These studies are performed on groups of patients large enough to identify clinically significant responses and usually last about three years. This concept includes phase III studies conducted in both the U.S. and in other countries.	Clinical Trials, Phase 3 as Topic,Drug Evaluation, FDA Phase 3 as Topic,Drug Evaluation, FDA Phase III as Topic,Evaluation Studies, FDA Phase 3 as Topic,Evaluation Studies, FDA Phase III as Topic