As another example, one isoform of MGRN1 with significant e

[jy9202]

0% of the dasatinib arm and ARN-509 溶解度 4. 3% of the imatinib arm. Of these, hematologic toxi city led to discontinuation in 1. 6% vs 1. 2%, and nonhema tologic toxicity led to discontinuation in 3. 5% vs 3. 1%, respectively. Median doses of drug delivered were 99 mg d in the dasatinib 100 mg QD arm vs 400 mg d in the imati nib 400 mg QD arm. Data for dose interruptions and reductions have not been reported, In the ENESTnd trial, discontinuations due to AEs occurred in 5% with nilotinib 300 mg BID, 9% with nilotinib 400 mg BID, and 7% with imatinib. Median doses of drug delivered were 592 mg d in the nilotinib 300 mg BID arm, 779 mg d in the nilotinib 400 mg BID arm, and 400 mg in the imatinib 400 mg QD arm. Respective rates of dose reduction inter ruption were 59%, 66%, and 52%.

Median cumulative durations AUY922 溶解度 of interruptions due to AEs or biochemical abnormalities were 19 days, 22 days, and 15 days, respec tively, Future directions with BCR ABL inhibitors Bosutinib Data are awaited from the randomized phase 3 trial of bosutinib vs imatinib for first line treatment for newly diagnosed CML, However, data have been reported for the efficacy and safety of bosutinib in patients with CP CML who had prior imatinib treatment. Response rates with bosutinib were comparable to those seen in trials of dasatinib and nilotinib in the second line setting, including CCyR in 50% and MMR in 52% of evaluated patients, of which 32% were complete. At 24 months, rates of progression free and overall survival were 80% and 95%, respectively. Responses were similar in patients with or without BCR ABL mutations.

Safety data indicate that bosutinib has a distinct safety profile compared with currently approved BCR ABL inhibitors. AE rates should ATP-competitive ALK 阻害剤 be interpreted with caution based on previous observa tions with dasatinib and nilotinib that AEs generally occur more frequently with second line treatment compared with first line treatment. Grade 3 4 thrombocytopenia, neutropenia, and anemia occurred in 24%, 16%, and 12%, respectively of patients receiving bosutinib. GI AEs were common with bosutinib treat ment, including diarrhea in 84% of patients, nausea in 44%, and vomiting in 36%, In addition, 34% of patients suffered from rash, 21% had abdominal pain, 21% had fatigue, 14% had headache, and 13% had joint pain, Rates of fluid retention AEs were not reported, indicating a frequency of 10%.

Of grade 3 4 biochemical abnorm alities, elevated ALT occurred in 10% of patients, elevated AST in 5%, elevated lipase in 7%, elevated glucose in 3%, decreased phosphate in 8%, and hypermagnesemia in 12%. In addition, 19% of patients receiving bosutinib in this study discontinued treatment due to AEs and 45% had a dose reduction due to AEs. The median dose of bosutinib was 454 mg d, Overall, preliminary data from this phase 1 2 trial indicate that bosutinib is an active agent for patients with CP CML who have failed on prior imatinib treatment, with activity against a range of BCR ABL mutations, and an acceptable toxicity profile.