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Blood, 15 May 2007, Vol. 109, No. 10, pp. 4110. This Article Full Text (PDF) 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 Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by O'Brien, S. Search for Related Content PubMed Articles by O'Brien, S. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS Comment on Guilhot et al, page 4143 Dasatinib in accelerated phase Stephen O'Brien NEWCASTLE UNIVERSITY The paper by Guilhot and colleagues extends the reported clinical experience with dasatinib in describing the outcome of 107 chronic myeloid leukemia (CML) patients treated with the drug in accelerated phase having failed, or been intolerant of, imatinib. Although the follow-up is quite short (8 months minimum), the results are encouraging even in this difficult phase of the disease. The long-term durability of responses to imatinib in patients with early chronic-phase CML has recently been reported,1 and thankfully the occurrence of drug resistance in this group of patients remains low. In chronic-phase patients who do develop imatinib resistance or intolerance, dasatinib has been shown to be effective salvage therapy,2 producing complete hematologic response (CHR) and major cytogenetic response (MCR) rates of 90% and 52%, respectively.3 Dasatinib has also been shown to be superior to higher-dose imatinib (800 mg) in rescuing patients failing on imatinib 400 mg.4 The data presented in this issue describe CHR and MCR rates in accelerated phase of 39% and 33%, respectively, with 24% managing to achieve a complete cytogenetic response (CCR)—quite an achievement in this difficult group of patients. The follow-up is short and so far of 69 patients who achieved good hematologic responses, 7 have progressed. The durability of the responses is, of course, still uncertain until longer follow-up is reported. The Achilles heel of both dasatinib and nilotinib is that neither of these promising new drugs is effective against leukemia cells harboring the T315I ABL kinase domain mutation. A longer-term concern, especially with advanced CML, is whether clones will inevitably emerge with this mutation and be a harbinger of inevitable drug resistance. Progress in CML drug therapy still continues at quite a remarkable pace: last month in Blood the first clinical data on MK-0457,5 a drug that does seem to be effective against T315I, were published. Other promising agents are in development. So where do we go next in the drug treatment of CML? Dasatinib is now licensed in many countries and nilotinib may well follow before too long. Other new agents may well become available to prescribers in the next few years. We face some tough challenges: the cost of these new agents is high, presenting considerable difficulties to health funders, patients, and physicians in terms of access to effective treatment. We also need to think carefully about how to use these agents logically in terms of both clinical and cost effectiveness. Comparative studies that address not only efficacy but also quality of life and health economic considerations will certainly be required. Footnotes Conflict-of-interest disclosure: The author has received research funds for clinical trials from Bristol Myers Squibb, Roche, and Novartis. REFERENCES Druker BJ, Guilhot F, O'Brien SG, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 2006; 355:2408–2417.[Abstract/Free Full Text] Talpaz M, Shah NP, Kantarjian H, et al. Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med 2006; 354:2531–2541.[Abstract/Free Full Text] Hochhaus A, Kantarjian HM, Baccarani M, et al. Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy. Prepublished on November 30, 2006, as DOI 10.1182/blood-2006-09-047266 (Now available as Blood. 2007;109:2303-2309.).[Abstract/Free Full Text] Kantarjian H, Pasquini R, Hamerschlak N, et al. Dasatinib or high-dose imatinib for chronic-phase chronic myeloid leukemia after failure of first-line imatinib: a randomized phase-II trial. Blood Prepubished on February 22, 2007, as DOI 10.1182/blood-2006-11-056028.[Abstract/Free Full Text] Giles FJ, Cortes J, Jones D, et al. MK-0457, a novel kinase inhibitor, is active in patients with chronic myeloid leukemia or acute lymphocytic leukemia with the T315I BCR-ABL mutation. Blood 2007; 109:500–502.[Abstract/Free Full Text] CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Dasatinib induces significant hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in accelerated phase Francois Guilhot, Jane Apperley, Dong-Wook Kim, Eduardo O. Bullorsky, Michele Baccarani, Gail J. Roboz, Sergio Amadori, Carmino A. de Souza, Jeffrey H. Lipton, Andreas Hochhaus, Dominik Heim, Richard A. Larson, Susan Branford, Martin C. Muller, Prasheen Agarwal, Ashwin Gollerkeri, and Moshe Talpaz Blood 2007 109: 4143-4150. [Abstract] [Full Text] [PDF] This Article Full Text (PDF) 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 Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by O'Brien, S. Search for Related Content PubMed Articles by O'Brien, S. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?

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