These mutations are therefore insensitive to dasatinib. With regard to individu

In the IRIS study of first line treatment with imatinib or inter feron and cytarabine in patients with newly diagnosed chronic phase CML, patients in the imatinib arm had an 8 year overall survival rate of 85% and freedom from progression to advanced disease was 92%, Ima tinib was also generally well tolerated during long term treatment. Despite the responses observed Amuvatinib 価格 with imatinib, a propor tion of patients develops resistance to imatinib or cannot tolerate its side effects.<br><br> This led to the development of newer tyrosine kinase inhibitors of BCR ABL, including dasatinib, nilotinib, and bosutinib, that were initially tested in clinical studies of patients with prior ima tinib therapy, Dasatinib, nilotinib and bosutinib, respectively, have 325 fold, AT-406 msds 20 30 fold, and 30 fold increased potency over imatinib against BCR ABL kinase in vitro, Nilotinib has a similar chemical structure to imatinib but has an improved topographical fit in the ABL kinase pocket, Dasatinib has a completely different chemical structure to imatinib and, unlike imatinib and nilotinib, binds BCR ABL in the active conformation, Bosutinib binds to an intermediate form of BCR ABL, All three TKIs have activity against most of the mutated forms of BCR ABL kinase that have been asso ciated with clinical resistance to imatinib, Dasatinib 100 mg once daily and nilotinib 400 mg twice daily have been approved in the US and Europe as treat ments for patients with CML who are resistant or intoler ant to imatinib, Dasatinib 100 mg QD and nilotinib 300 mg BID were recently approved in the US for patients with newly diagnosed CP CML.<br><br> Bosutinib is still undergoing clinical trials. Clinical trials assessing the newer TKIs as first line therapies in newly diag nosed CP CML are ongoing and results from trials of dasatinib and nilotinib have recently been reported. For dasatinib, published clinical trials in newly diagnosed CP AG-490 価格 CML comprise: DASISION, an international, multicenter, randomized phase 3 trial of dasatinib 100 mg QD vs imatinib 400 mg QD, and a single arm phase 2 trial of dasatinib 100 mg QD or 50 mg BID performed by M D Anderson Cancer Center, Houston, TX, For nilotinib, pub lished clinical trials in newly diagnosed CP CML com prise: ENESTnd, an international, multicenter, randomized phase 3 trial of nilotinib 300 mg BID vs nilotinib 400 mg BID vs imatinib 400 mg QD, a single arm phase 2 trial of nilotinib 400 mg BID performed by MDACC, and a second single arm phase 2 trial of niloti nib 400 mg BID performed by the Italian GIMEMA group, No data have been published from an international, multicenter, randomized trial of bosutinib vs imatinib, In this review, recent data for first line treatment with dasatinib or nilotinib will be discussed, with a specific focus on safety and tolerability.<br><br> Efficacy of dasatinib and nilotinib compared with imatinib in the first line setting In randomized trials, both dasatinib and nilotinib have shown superior efficacy compared with imatinib as first line treatment for patients with CP CML, In the DASISION trial, responses were more frequent with dasatinib vs imatinib treatment, including higher 12 month rates of complete cytogenetic response and major molecular response, Dasatinib also showed superiority over imatinib in the primary trial endpoint, the rate of confirmed CCyR, with 12 month rates of 77% vs 66%, respectively, CCyR and MMR both occurred faster with dasatinib compared with imatinib.