title: Dose-finding study of imatinib in combination with intravenous cytarabine: feasibility in newly diagnosed patients with chronic myeloid leukemia.
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.
authors.affiliation: Department of Hematology, Erasmus University Medical Center, Groene Hilledijk 301, Rotterdam, The Netherlands.
authors.forename: Wendy
authors.initials: W
authors.lastname: Deenik
authors.forename: Bronno
authors.initials: B
authors.lastname: van der Holt
authors.forename: Gregor E G
authors.initials: GE
authors.lastname: Verhoef
authors.forename: Willem M
authors.initials: WM
authors.lastname: Smit
authors.forename: Marie J
authors.initials: MJ
authors.lastname: Kersten
authors.forename: Hanneke C
authors.initials: HC
authors.lastname: Kluin-Nelemans
authors.forename: Leo F
authors.initials: LF
authors.lastname: Verdonck
authors.forename: Augustin
authors.initials: A
authors.lastname: Ferrant
authors.forename: Anton V M B
authors.initials: AV
authors.lastname: Schattenberg
authors.forename: Jeroen J W M
authors.initials: JJ
authors.lastname: Janssen
authors.forename: Pieter
authors.initials: P
authors.lastname: Sonneveld
authors.forename: Marinus
authors.initials: M
authors.lastname: van Marwijk Kooy
authors.forename: Shulamit
authors.initials: S
authors.lastname: Wittebol
authors.forename: Roelof
authors.initials: R
authors.lastname: Willemze
authors.forename: Pierre W
authors.initials: PW
authors.lastname: Wijermans
authors.forename: Petra H M
authors.initials: PH
authors.lastname: Westveer
authors.forename: H Berna
authors.initials: HB
authors.lastname: Beverloo
authors.forename: Peter
authors.initials: P
authors.lastname: Valk
authors.forename: Bob
authors.initials: B
authors.lastname: Löwenberg
authors.forename: Gert J
authors.initials: GJ
authors.lastname: Ossenkoppele
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Cornelissen
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001549:Benzamides; D003141:Communicable Diseases / Q000150:complications; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D020732:Cytogenetic Analysis; D004305:Dose-Response Relationship, Drug; D005240:Feasibility Studies; D005260:Female; D006403:Hematologic Tests; D006801:Humans; D000068877:Imatinib Mesylate; D007275:Injections, Intravenous; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009026:Mortality; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D003561:Cytarabine; D000068877:Imatinib Mesylate