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Original Article
Dasatinib or high-dose imatinib for chronic-phase chronic myeloid leukemia resistant to imatinib at a dose of 400 to 600 milligrams daily†‡
Two-year follow-up of a randomized phase 2 study (START-R)
Article first published online: 17 JUN 2009
DOI: 10.1002/cncr.24504
Copyright © 2009 American Cancer Society
Additional Information
How to Cite
Kantarjian, H., Pasquini, R., Lévy, V., Jootar, S., Holowiecki, J., Hamerschlak, N., Hughes, T., Bleickardt, E., Dejardin, D., Cortes, J. and Shah, N. P. (2009), Dasatinib or high-dose imatinib for chronic-phase chronic myeloid leukemia resistant to imatinib at a dose of 400 to 600 milligrams daily. Cancer, 115: 4136–4147. doi: 10.1002/cncr.24504
- †
Presented previously in part as an oral presentation at the 49th Annual Meeting and Exposition of the American Society of Hematology, Atlanta, Georgia, December 8-11, 2007; and as a poster presentation at the 44th Annual Meeting of the American Society of Clinical Oncology, Chicago, Illinois, May 30 to June 3, 2008; and at the 13th Congress of the European Hematology Association, Copenhagen, Denmark, June 12-15, 2008.
- ‡
The following principal investigators, in addition to the authors, also participated in the CA180-017 study: J. J. Garcia, I. Otero, and D. Riveros (Argentina); C. Arthur (Australia); A. Bosly and W. Schroyens (Belgium); P. E. Dorlhiac Llacer and A. Moellman Coelho (Brazil); S. Assouline, D. Forrest, C. Gambacorti-Passerini, P. Laneuville, and A. Turner (Canada); M. Varik (Estonia); K. Porkka (Finland); T. Facon, F. Guilhot, M. Michalet, J. Reiffers, and P. Rousselot (France); C. Bokemeyer, A. Hochhaus, and D. Niederwieser (Germany); T. Masszi (Hungary); A. Nagler (Israel); D. W. Kim (Korea); H. Hjorth-Hansen (Norway); L. Casanova and J. Navarro (Peru); P. Caguioa (Philippines); A. Dmoszynska, W. Jedrzejczak, A. Hellmann, T. Robak, and A. Skotnicki (Poland); F. Cabanillas (Puerto Rico); N. Khoroshko, A. Zaritsky, and A. Golenkov (Russia); J. Lombard, P. Ruff, and G. Cohen (South Africa); L. Stenke and H. Wadenvik (Sweden); L. Y. Shih (Taiwan); J. Apperley, T. Holyoake, and S. O'Brien (United Kingdom); and J. Dipersio, J. K. Giguere, R. Lloyd, J. McGuirk, M. S. Murali, R. M. Stone, and R. Paquette (United States). In addition, K. Gialelis served as protocol manager, and A. Zhao and E. Cormier served as protocol data managers.
Publication History
- Issue published online: 4 SEP 2009
- Article first published online: 17 JUN 2009
- Manuscript Accepted: 10 FEB 2009
- Manuscript Received: 17 DEC 2008
Funded by
- Bristol-Myers Squibb
- Novartis
- Wyeth
References
- 1National Comprehensive Cancer Network, Inc. The Chronic Myelogenous Leukemia Clinical Practice Guidelines in Oncology. Version 1.2009. Available at http://www.nccn.org. Accessed August 29, 2008.
- 2, , , et al. Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood. 2006; 108: 1809–1820.
- 3, , , et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2003; 348: 994–1004.
- 4. BCR-ABL tyrosine kinase inhibitors for chronic myelogenous leukemia. N Engl J Med. 2007; 357: 258–265.
- 5, , , et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006; 355: 2408–2417.
- 6, . Clinical resistance to imatinib: mechanisms and implications. Hematol Oncol Clin North Am. 2004; 18: 641–656.
- 7, , , et al. Dose escalation of imatinib mesylate can overcome resistance to standard-dose therapy in patients with chronic myelogenous leukemia. Blood. 2003; 101: 473–475.
- 8, , , et al. Favorable long-term follow-up results over 6 years for response, survival, and safety with imatinib mesylate therapy in chronic-phase chronic myeloid leukemia after failure of interferon-alpha treatment. Blood. 2008; 111: 1039–1043.
- 9, , , et al. Impact of imatinib mesylate dose escalation on resistance and suboptimal responses to standard-dose therapy in patients (pts) with chronic myeloid leukemia (CML) [abstract]. Blood. 2007; 110: 313a–314a. Abstract 1035.
- 10, , , et al. Imatinib dose escalation is effective in patients with chronic myeloid leukemia in chronic phase (CML-CP) [abstract]. Blood. 2007; 110: 317a. Abstract 1047.
- 11, , , et al. Transient benefit only from increasing the imatinib dose in CML patients who do not achieve complete cytogenetic remissions on conventional doses. Blood. 2003; 102: 2702–2703.
- 12, , , et al. The effect of dose increase of imatinib mesylate in patients with chronic or accelerated phase chronic myelogenous leukemia with inadequate hematologic or cytogenetic response to initial treatment. Clin Cancer Res. 2003; 9: 2092–2097.
- 13, , , et al. In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants. Cancer Res. 2005; 65: 4500–4505.
- 14, , , et al. Overriding imatinib resistance with a novel ABL kinase inhibitor. Science. 2004; 305: 399–401.
- 15, , , et al. Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy. Blood. 2007; 109: 2303–2309.
- 16, , , et al. Dasatinib induces durable cytogenetic responses in patients with chronic myelogenous leukemia in chronic phase with resistance or intolerance to imatinib. Leukemia. 2008; 22: 1200–1206.
- 17, , , et al. Dasatinib or high-dose imatinib for chronic-phase chronic myeloid leukemia after failure of first-line imatinib: a randomized phase 2 trial. Blood. 2007; 109: 5143–5150.
- 18, , , et al. Intermittent target inhibition with dasatinib 100 mg once daily preserves efficacy and improves tolerability in imatinib-resistant and -intolerant chronic-phase chronic myeloid leukemia. J Clin Oncol. 2008; 26: 3204–3212.
- 19, , , et al. Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med. 2006; 354: 2531–2541.
- 20, , , et al. Dasatinib 2-year efficacy in patients with chronic-phase chronic myelogenous leukemia (CML-CP) with resistance or intolerance to imatinib (START-C) [abstract]. J Clin Oncol. 2008; 26: 374s. Abstract 7009.
- 21, , , et al. Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia. N Engl J Med. 2003; 349: 1423–1432.
- 22, , , et al. Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results. Blood. 2006; 108: 28–37.
- 23, . The use of confidence or fiducial limits illustrated in the case of the binomial. Biometrika. 1934; 26: 404–413.
- 24, . On small-sample confidence intervals for parameters in discrete distributions. Biometrics. 2001; 57: 963–971.Direct Link:
- 25, . A confidence interval for the median survival time. Biometrics. 1982; 38: 29–41.
- 26, , , et al. Interferon alfa-2b combined with cytarabine versus interferon alone in chronic myelogenous leukemia. N Engl J Med. 1997; 337: 223–229.
- 27, , , et al. Imatinib for newly diagnosed patients with chronic myeloid leukemia: incidence of sustained responses in an intention-to-treat analysis. J Clin Oncol. 2008; 26: 3358–3363.
- 28, , . The development of imatinib as a therapeutic agent for chronic myeloid leukemia. Blood. 2005; 105: 2640–2653.

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