Something About Dasatinib that You May not Know

  • Dasatinib, alias DASA Tin IB, is a gray to yellow solid chemical. Dasatinib is an anti-tumor drug that is clinically the primary treatment for imatinib mesylate-resistant, or intolerant adult chromosomes of chronic chromosome-positive chronic myeloid leukemia in the chronic phase, accelerated phase, and blast phase.


    Clinical application


    Dasatinib can be used in adult patients who have been treated for all stages of chronic myelogenous leukemia that are resistant or intolerant of imatinib mesylate. At the same time, the FDA has also approved cd184 antibody for the treatment of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia who are resistant or intolerant to other therapies through normal procedures.


    Dasatinib is a polytyrosine kinase inhibitor, which was approved for use based on safety and efficacy results from four international, multicenter, phase II trials involving a total of 911 patients and other supporting data. The above two indications. The most commonly reported side effects in clinical studies are fluid retention, gastrointestinal symptoms, and bleeding events; the most frequently reported severe side effects are fever, pleural effusion, and febrile neutral white for granulocytic leukemia.


    On June 29, the FDA approved Bristol-Myers Squibb's Sprycel (dasatinib) for adult patients to treat two new indications: chronic myeloid leukemia (CML) that is insensitive to first-line chemotherapy such as imatinib (CML) ), as well as Ph chromosome-positive acute lymphoblastic leukemia (ALL) that is ineffective or intolerant to other therapies.


    Among the approved drugs, sprycel is the first oral chemotherapeutic drug capable of inhibiting multiple configurations of the tyrosine protein kinase Abl. At nanomolar concentrations, the drug inhibits multiple kinases such as the Bcr-Abl, SRC kinase family, c-KIT, EPHA2, and PDGFR-B. By inhibiting the action of the above kinases, Sprycel inhibits the proliferation of leukemia cells in CML and Ph+ ALL bone marrow, but normal red blood cells, white blood cells and platelets can continue to proliferate.


    Previously, the gold standard for the treatment of CML was imatinib, but some patients were resistant, and as the number of years of treatment increased and the condition worsened, the incidence of drug resistance increased, while patients with advanced Ph-positive ALL (including In the primordial phase, resistance to imatinib is faster, due to sequence coding of Bcr-Abl kinase, overexpression of drug cxcl10 antibody resistance genes, or activation of non-Bcr kinase signaling pathways such as SRC.


    Sprycel's main adverse reactions include: bone marrow suppression, hemorrhage, fluid retention, and prolonged QT interval.


    In vitro studies, dasatinib is active in leukemia cell lines expressing various imatinib-sensitive and drug-resistant diseases. The results of these non-clinical studies indicate that dasatinib can overcome imatinib resistance caused by BCR-ABL overexpression, BCR-ABL kinase domain mutations, and kinases including SRC family kinases (LYN, HCK). Other signaling pathways within, as well as overexpression of multidrug resistance genes. In addition, dasatinib inhibits SRC family kinases at this nanomolar concentration.


    Adverse reactions


    Most of the adverse reactions to dasatinib treatment were mild to moderate. Most patients with chronic CML who are intolerant to imatinib are able to tolerate dasatinib. The most common adverse reactions include fluid retention, diarrhea, headache, nausea, rash, difficulty breathing, bleeding, fatigue, musculoskeletal pain, infection, vomiting, cough, abdominal pain, and fever. The incidence of drug-related febrile neutropenia was 5%.