DNA-PK Inhibitors incidences of fluid retention and superficial edema were observed in patients treated

the rate of confirmed CCyR by 12 months was significantly higher in patients who received dasatinib compared with those who received imatinib. The rate ofMMRat any time was also significantly higher in patients who received dasatinib Fluorouracil compared with those who received imatinib, as was the rate of MMR at 12 months. Rates of CCyR at 3, 6, and 9 months were 54%, 73%, and 78% for dasatinib treatment compared with 31%, 59%, and 67% for imatinib treatment, respectively. Times to CCyR and confirmed CCyR were significantly shorter for dasatinib compared with imatinib. Rates of MMR at 3, 6, and 9 months were 8%, 27%, and 39% for dasatinib compared with 0.4%, 8%, and 18% for imatinib, respectively. The time to MMR was also significantly shorter with dasatinib versus imatinib.
At 12 months, the estimated rates of PFS and OS were similar in both treatment groups.57 After a median follow hts screening up of 24 months, rates of confirmed CCyR, standard definition CCyR, and MMR remained higher in the dasatinib arm than in the imatinib arm. Rates for PFS and OS at 24 months in the dasatinib arm were 93.7% and 95.3%, respectively, and rates for PFS and OS in the imatinib arm were 92.1% and 95.2%, respectively.59 Although drug concentrations and treatment outcomes might have been affected by nonadherence to therapy, drug concentrations were not reported in this study.59 The majority of drug related AEs were grade 1 or 2 for both dasatinib and imatinib. The incidence of grade 3 to 4 neutropenia was similar: 21% in the dasatinib group and 20% in the imatinib group after a minimum follow up of 12 months.
The rate of grade 3 to 4 thrombocytopenia was 19% among dasatinib treated patients and 10% among imatinib treated patients. Most DNA-PK inhibitor in clinical trials nonhematologic AEs occurred less frequently in patients treated with dasatinib compared with those treated with imatinib. These in cluded nausea, vomiting, muscle inflammation, Irbesartan 138402-11-6 and rash. Higher incidences of fluid retention and superficial edema were observed in patients treated with imatinib compared with those treated with dasatinib. Grade 1 to 2 pleural effusion was observed in 10% of patients treated with dasatinib, of these patients, 92% had a CCyR by 12 months.57 A similar tolerability profile was observed after a median follow up of 24 months. Most cytopenias were reported within 4 months. The incidence of grade 3 pleural effusion was 1%.
59 Based on data from the DASISION trial, the US Food and Drug Administration and the European Medicines Agency approved dasatinib for adults brain with newly diagnosed Philadelphia chromosome positive CML CP.13 Other Studies A search of www.clinicaltrials.gov identified other studies of dasatinib that are underway in patients with newly diagnosed disease. A third comparative Phase II study is investigating the depletion of Ph stem cells after 6 months of treatment with dasatinib 100 mg once daily versus imatinib 400 mg once daily.60 An additional Phase II study is currently investigating CCyR rates of dasatinib in children and adolescents, including those with newly diagnosed CML CP.61 A further Phase II study is assessing the rate of complete molecular response at 12 months in Japanese patients receiving dasatinib 100 mg once daily.62 A second Phase III randomized study, based in the United Kingdom.