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 cytara- bine (200 mg/m2or 1000 mg/m2days 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 werecaused bystreptococcal bacteremia in 5 cases. Intermediate-dose cytarabine (1000 mg/m2) prolonged time to neutro- phil recovery and platelet recovery compared with a standard dose (200 mg/m2). 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 cytara- bine compared with a standard-dose of cytarabine. Early response data after combination therapy included a complete cy-togenetic 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 no. CKTO- 2001-03.

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Persistent URL dx.doi.org/10.1182/blood-2007-08-107482, hdl.handle.net/1765/28746
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Deenik, W., van Holt, B.D., Verhoef, G.E.G., Smit, W.F., Kersten, M.J., Kluin-Nelemans, H.C., … Cornelissen, J.J.. (2008). Dose-finding study of imatinib in combination with intravenous cytarabine: Feasibility in newly diagnosed patients with chronic myeloid leukemia. Blood, 111(5), 2581–2588. doi:10.1182/blood-2007-08-107482