Dose-finding study of imatinib in combination with intravenous cytarabine: feasibility in newly diagnosed patients with chronic myeloid leukemia.

Deenik, Wendy;van der Holt, Bronno;Verhoef, Gregor E G;Smit, Willem M;Cornelissen, Jan J;et.al.
(2008) Blood — Vol. 111, n° 5, p. 2581-2588 (2008)

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Authors
  • Deenik, Wendy
    Author
  • van der Holt, Bronno
    Author
  • Verhoef, Gregor E G
    Author
  • Smit, Willem M
    Author
  • Ferrant, AugustinUCLouvain
    Author
  • Cornelissen, Jan J
    Author
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Abstract
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 www.kankerbestrijding.nl as no. CKTO-2001-03.
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Deenik, W., van der Holt, B., Verhoef, G. E. G., Smit, W. M., Kersten, M. J., Kluin-Nelemans, H. C., Verdonck, L. F., Ferrant, A., Schattenberg, A. V. M. B., Janssen, J. J. W. M., Sonneveld, P., van Marwijk Kooy, M., Wittebol, S., Willemze, R., Wijermans, P. W., Westveer, P. H. M., Beverloo, H. B., Valk, P., Löwenberg, B., et al. (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. https://doi.org/10.1182/blood-2007-08-107482 (Original work published 2008)