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Blood, 15 November 2008, Vol. 112, No. 10, pp. 3965-3973. Prepublished online as a Blood First Edition Paper on September 3, 2008; DOI 10.1182/blood-2008-06-161737. This Article Full Text Full Text (PDF) Supplemental Appendix All Versions of this Article: blood-2008-06-161737v1 112/10/3965    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hughes, T. P. Articles by Grigg, A. Search for Related Content PubMed PubMed Citation Articles by Hughes, T. P. Articles by Grigg, A. Related Collections Neoplasia Free Research Articles Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS Impact of early dose intensity on cytogenetic and molecular responses in chronic- phase CML patients receiving 600 mg/day of imatinib as initial therapy Timothy P. Hughes1,2, Susan Branford1,2, Deborah L. White1,2, John Reynolds2, Rachel Koelmeyer2, John F. Seymour2, Kerry Taylor2, Chris Arthur2, Anthony Schwarer2, James Morton2, Julian Cooney2, Michael F. Leahy2, Philip Rowlings2, John Catalano2, Mark Hertzberg2, Robin Filshie2, Anthony K. Mills2, Keith Fay2, Simon Durrant2, Henry Januszewicz2, David Joske2, Craig Underhill2, Scott Dunkley2, Kevin Lynch3, Andrew Grigg2, on behalf of the Australasian Leukaemia and Lymphoma Group 1 Institute of Medical and Veterinary Science, Adelaide; 2 Australasian Leukaemia and Lymphoma Group; and 3 Novartis Pharmaceuticals Australia, Sydney, Australia We conducted a trial in 103 patients with newly diagnosed chronic phase chronic myeloid leukemia (CP-CML) using imatinib 600 mg/day, with dose escalation to 800 mg/day for suboptimal response. The estimated cumulative incidences of complete cytogenetic response (CCR) by 12 and 24 months were 88% and 90%, and major molecular responses (MMRs) were 47% and 73%. In patients who maintained a daily average of 600 mg of imatinib for the first 6 months (n = 60), MMR rates by 12 and 24 months were 55% and 77% compared with 32% and 53% in patients averaging less than 600 mg (P = .037 and .016, respectively). Dose escalation was indicated for 17 patients before 12 months for failure to achieve, or maintain, major cytogenetic response at 6 months or CCR at 9 months but was only possible in 8 patients (47%). Dose escalation was indicated for 73 patients after 12 months because their BCR-ABL level remained more than 0.01% (international scale) and was possible in 45 of 73 (62%). Superior responses achieved in patients able to tolerate imatinib at 600 mg suggests that early dose intensity may be critical to optimize response in CP-CML. The trial was registered at www.ANZCTR.org.au as #ACTRN12607000614493. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Baccarani, G. Rosti, F. Castagnetti, I. Haznedaroglu, K. Porkka, E. Abruzzese, G. Alimena, H. Ehrencrona, H. Hjorth-Hansen, V. Kairisto, et al. Comparison of imatinib 400 mg and 800 mg daily in the front-line treatment of high-risk, Philadelphia-positive chronic myeloid leukemia: a European LeukemiaNet Study Blood, May 7, 2009; 113(19): 4497 - 4504. [Abstract] [Full Text] [PDF] F. Castagnetti, F. Palandri, M. Amabile, N. Testoni, S. Luatti, S. Soverini, I. Iacobucci, M. Breccia, G. Rege Cambrin, F. Stagno, et al. Results of high-dose imatinib mesylate in intermediate Sokal risk chronic myeloid leukemia patients in early chronic phase: a phase 2 trial of the GIMEMA CML Working Party Blood, April 9, 2009; 113(15): 3428 - 3434. [Abstract] [Full Text] [PDF] D. Bixby and M. Talpaz Imatinib As Frontline Therapy for Patients with Newly Diagnosed Chronic-phase Chronic Myeloid Leukemia ASCO Educational Book, January 1, 2009; 2009(1): 395 - 401. [Abstract] [Full Text] [PDF]

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