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Blood, 1 March 2008, Vol. 111, No. 5, pp. 2581-2588. Prepublished online as a Blood First Edition Paper on January 2, 2008; DOI 10.1182/blood-2007-08-107482. This Article Full Text (PDF) All Versions of this Article: blood-2007-08-107482v1 111/5/2581    most recent Alert me when this article is cited Alert me if a correction is posted 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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Deenik, W. Articles by Cornelissen, J. J. Search for Related Content PubMed PubMed Citation Articles by Deenik, W. Articles by Cornelissen, J. J. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 16, 2007 Accepted December 14, 2007 Dose finding study of imatinib in combination with intravenous cytarabine: feasibility in newly diagnosed patients with chronic myeloid leukemia Wendy Deenik, Bronno van der Holt, Gregor E.G. Verhoef, Willem M. Smit, Marie J. Kersten, Hanneke C Kluin-Nelemans, Leo F Verdonck, Augustin Ferrant, Anton V.M.B. Schattenberg, Jeroen J.W.M. Janssen, Pieter Sonneveld, Marinus van Marwijk Kooy, Shulamit Wittebol, Roelof Willemze, Pierre W. Wijermans, Petra H.M. Westveer, H. Berna Beverloo, Peter Valk, Bob Lowenberg, Gert J. Ossenkoppele, and Jan J. Cornelissen* Erasmus University Medical Center, Rotterdam, Netherlands University Hospital Gasthuisberg, Leuven, Belgium Medical Spectrum Twente, Enschede, Netherlands Hematology, Academic Medical Center, Amsterdam, Netherlands University Hospital Groningen, Groningen, Netherlands University Medical Center Utrecht, Utrecht, Netherlands University Hospital St-Luc, Brussels, Belgium Radboud University Nijmegen Medical Center, Nijmegen, Netherlands VU Medical Center, Amsterdam, Netherlands Isala Clinic-Sophia, Zwolle, Netherlands Meander Medical Center, Amersfoort, Netherlands Leiden University Medical Center, Leiden, Netherlands Haga Hospital, The Hague, Netherlands * Corresponding author; email: j.cornelissen{at}erasmusmc.nl. The HOVON cooperative study group performed a feasibility study of escalated imatinib and intravenous cytarabine in 165 patients with early chronic phase chronic myeloid leukemia (CML). Patients received two cycles of intravenous cytarabine (200 mg/m2 or 1000 mg/m2 days 1-7) in conjunction with imatinib (200 mg, 400 mg, 600 mg or 800 mg), according to predefined, successive dose levels. All dose levels proved feasible. Seven dose limiting toxicities (DLTs) were observed in 302 cycles of chemotherapy, which were caused by streptococcal bacteremia in five cases. Intermediate-dose cytarabine (1000 mg/m2) prolonged time to neutrophil recovery and platelet recovery as compared to a standard-dose (200 mg/m2). High-dose imatinib (600 mg or 800 mg) extended the time to platelet recovery as compared to a standard-dose (400 mg). More infectious complications common toxicity criteria (CTC) grade 3-4 were observed after intermediate-dose cytarabine as compared to a standard-dose of cytarabine. Early response data after combination therapy included a complete hematologic cytogenetic response in 48% and a major molecular response in 30% of patients, which increased to 46% major molecular responses at 1 year, including 13% complete molecular responses. We conclude that combination therapy of escalating dosages of imatinib and cytarabine is feasible. This study was registered at www.kankerbestrijding.nl as #CKTO-2001-03. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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