Dasatinib or high‐dose imatinib for chronic‐phase chronic myeloid leukemia resistant to imatinib at a dose of 400 to 600 milligrams daily |
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| Authors: | Hagop Kantarjian MD Ricardo Pasquini MD Vincent Lévy MD PhD Saengsuree Jootar MD Jerzy Holowiecki MD PhD Nelson Hamerschlak MD PhD Timothy Hughes MD Eric Bleickardt MD David Dejardin MSc Jorge Cortes MD Neil P. Shah MD PhD |
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| Affiliation: | 1. Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas;2. Fax: (713) 794‐4297;3. Hospital De Clinicas De Curitiba, Parana, Brazil;4. Clinical Investigation Center, AP‐HP, INSERM U9504, H?pital Saint‐Louis, Paris, France;5. Ramathibodi Hospital, Mahidol University, Bangkok, Thailand;6. University Hospital‐SPSKM, Katowice, Poland;7. Hospital Israelita Albert Einstein, Sao Paulo, Brazil;8. Division of Hematology, Institute of Medical and Veterinary Science, Adelaide, South Australia, Australia;9. Bristol‐Myers Squibb, Wallingford, Connecticut;10. Division of Hematology and Oncology, University of California at San Francisco School of Medicine, San Francisco, California |
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| Abstract: | BACKGROUND: In patients with chronic‐phase chronic myeloid leukemia (CP‐CML), imatinib resistance is of increasing importance. Imatinib dose escalation was the main treatment option before dasatinib, which has 325‐fold more potent inhibition than imatinib against unmutated Bcr‐Abl in vitro. Data with a minimum of 2 years of follow‐up were available for the current study of dasatinib and high‐dose imatinib in CP‐CML resistant to imatinib at daily doses from 400 mg to 600 mg. METHODS: A phase 2, open‐label study was initiated of 150 patients with imatinib‐resistant CP‐CML who were randomized (2:1) to receive either dasatinib 70 mg twice daily (n = 101) or high‐dose imatinib 800 mg (400 mg twice daily; n = 49). RESULTS: At a minimum follow‐up of 2 years, dasatinib demonstrated higher rates of complete hematologic response (93% vs 82%; P = .034), major cytogenetic response (MCyR) (53% vs 33%; P = .017), and complete cytogenetic response (44% vs 18%; P = .0025). At 18 months, the MCyR was maintained in 90% of patients on the dasatinib arm and in 74% of patients on the high‐dose imatinib arm. Major molecular response rates also were more frequent with dasatinib than with high‐dose imatinib (29% vs 12%; P = .028). The estimated progression‐free survival also favored dasatinib (unstratified log‐rank test; P = .0012). CONCLUSIONS: After 2 years of follow‐up, dasatinib demonstrated durable responses and improved response and progression‐free survival rates relative to high‐dose imatinib. Cancer 2009. © 2009 American Cancer Society. |
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| Keywords: | dasatinib drug resistance imatinib chronic myeloid leukemia |
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