Brian L Abbott1. 1. Department of Medical Oncology, Sletten Cancer Institute, Great Falls, Montana 59405, USA.
Abstract
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. OBJECTIVES: 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.
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-ABLimatinib resistance. OBJECTIVES: 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.
Authors: Daniela Hoehn; Jorge E Cortes; L Jeffrey Medeiros; Elias J Jabbour; Juliana E Hidalgo; Rashmi Kanagal-Shamanna; Carlos E Bueso-Ramos Journal: Clin Lymphoma Myeloma Leuk Date: 2016-08
Authors: Yen Min Huang; Cheng Hsu Wang; Jen Seng Huang; Kun Yun Yeh; Chien Hong Lai; Tsung Han Wu; Pei Hung Chang; Pei Hung Chang; Yueh Shih Chang; Yii Jenq Lan Journal: Turk J Haematol Date: 2015-03-05 Impact factor: 1.831