TY - JOUR
T1 - Dose-finding study of imatinib in combination with intravenous cytarabine: feasibility in newly diagnosed patients with chronic myeloid leukemia
AU - Deenik, Wendy
AU - van der Holt, Bronno
AU - Verhoef, Gregor E. G.
AU - Smit, Willem M.
AU - Kersten, Marie J.
AU - Kluin-Nelemans, Hanneke C.
AU - Verdonck, Leo F.
AU - Ferrant, Augustin
AU - Schattenberg, Anton V. M. B.
AU - Janssen, Jeroen J. W. M.
AU - Sonneveld, Pieter
AU - van Marwijk Kooy, Marinus
AU - Wittebol, Shulamit
AU - Willemze, Roelof
AU - Wijermans, Pierre W.
AU - Westveer, Petra H. M.
AU - Beverloo, H. Berna
AU - Valk, Peter
AU - Löwenberg, Bob
AU - Ossenkoppele, Gert J.
AU - Cornelissen, Jan J.
AU - van Marwijk, K.M.
AU - Westveer, PH
AU - Lowenberg, B.
PY - 2008
Y1 - 2008
N2 - 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
AB - 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
U2 - https://doi.org/10.1182/blood-2007-08-107482
DO - https://doi.org/10.1182/blood-2007-08-107482
M3 - Article
C2 - 18172005
SN - 0006-4971
VL - 111
SP - 2581
EP - 2588
JO - Blood
JF - Blood
IS - 5
ER -