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 Löwenberg, Gert J. OssenkoppeleJan J. Cornelissen, K.M. van Marwijk, PH Westveer, B. Lowenberg

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21 Citations (Scopus)


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 2 cycles of intravenous cytarabine (200 mg/m(2) or 1000 mg/m(2) 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 5 cases. Intermediate-dose cytarabine (1000 mg/m(2)) prolonged time to neutrophil recovery and platelet recovery compared with a standard dose (200 mg/m(2)). High-dose imatinib (600 mg or 800 mg) extended the time to platelet recovery compared with a standard dose (400 mg). More infectious complications common toxicity criteria (CTC) grade 3 or 4 were observed after intermediate-dose cytarabine compared with a standard-dose of cytarabine. Early response data after combination therapy included a complete 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 as no. CKTO-2001-03
Original languageEnglish
Pages (from-to)2581-2588
Issue number5
Publication statusPublished - 2008

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