Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia
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4,369 citations
Cites background from "Five-year follow-up of patients rec..."
...By exploiting the genetic differences between normal cells and cancer cells, several molecular-targeted drugs, such as imatinib (Gleevec; Novartis) and trastuzumab (Herceptin; Genentech/Roche), show promising therapeutic activity and few toxic side effect...
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2,420 citations
Cites background from "Five-year follow-up of patients rec..."
...Accordingly, inhibition of the tyrosine kinase activity of the oncogenic BCR (breakpoint cluster region)– ABL1 fusion protein, formation of which is a causative transforming event in chronic myeloid leukaemia (CML), is a validated means for therapeutic interventio...
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2,187 citations
Cites background from "Five-year follow-up of patients rec..."
...Insets (1) and (2) are magnified views of selected highly significant associations; the drug name, therapeutically relevant target(s) (in superscript) and cancer gene (in brackets) are given for each....
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...PD0332991CDK4/6 (RB1) AxatinibPDGFR,KIT,VEGFR (BCR-ABL) AZD6244MEK (BRAF) GW441756NTRK1 (FLT3) WH-4-023SRC,ABL (CDKN2A) (2) (1) 1 × 10–28 (1)...
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2,158 citations
Cites background from "Five-year follow-up of patients rec..."
...For example, the use of drugs to target the protein product of the BCR–ABL translocation in chronic myeloid leukemia, or the BRAF gene in malignant melanoma, has transformed the treatment of these diseases and substantially improved survival rates (1,2)....
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1,679 citations
Cites background from "Five-year follow-up of patients rec..."
...It is recommended that in practice outside of clinical trials, the firstline treatment of CP CML can be any of the 3 TKIs that have been approved for this indication and are available nearly worldwide, namely imatinib (400mg once daily), nilotinib (300mg twice daily), and dasatinib (100 mg once daily)....
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...The use of TKI may require a change of the boundaries between CP, AP, and BP and modify to some extent the classic subdivision of CML in 3 phases, but the data are not yet sufficient for a revision....
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...For several years, dasatinib and nilotinib have been approved for second-line treatment of CML patients intolerant of or in whom imatinib treatment failed, based on reported CCyR rates of 40% to 60%.5,42 Two major companysponsored, phase 2, single-arm studies have been updated, reporting anMMR rate of 28% after 2 years (nilotinib)43,44 and 42% after 5 years (dasatinib)45,46; stability of the CCyR, once achieved; and PFS of 57% at 4 years with nilotinib44 and of 56% at 5 yearswith dasatinib.46 However, in both studies the proportion of patients who were still taking core treatment at 4 to 5 years was only 30% and 31%, respectively....
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...Currently, we recommend that a patient with CMLwho is responding optimally to treatment continues indefinitely at the standard recommended dose....
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...Several studies of imatinib as first-line therapy have been updated or newly reported.(15-39) The proportion of patients who achieved CCyR and MMRafter 1 year of 400mg imatinib daily ranged from 49% to 77%, and from 18% to 58%, respectively(23,24,26,35-39) (supplemental Table 1, available on the Blood website)....
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