title: Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study.
abstract: Chronic myelogenous leukemia (CML) is caused by expression of the BCR-ABL tyrosine kinase oncogene, the product of the t(9;22) Philadelphia translocation. Patients with CML in accelerated phase have rapidly progressive disease and are characteristically unresponsive to existing therapies. Imatinib (formerly STI571) is a rationally developed, orally administered inhibitor of the Bcr-Abl kinase. A total of 235 CML patients were enrolled in this study, of whom 181 had a confirmed diagnosis of accelerated phase. Patients were treated with imatinib at 400 or 600 mg/d and were evaluated for hematologic and cytogenetic response, time to progression, survival, and toxicity. Imatinib induced hematologic response in 82% of patients and sustained hematologic responses lasting at least 4 weeks in 69% (complete in 34%). The rate of major cytogenetic response was 24% (complete in 17%). Estimated 12-month progression-free and overall survival rates were 59% and 74%, respectively. Nonhematologic toxicity was usually mild or moderate, and hematologic toxicity was manageable. In comparison to 400 mg, imatinib doses of 600 mg/d led to more cytogenetic responses (28% compared to 16%), longer duration of response (79% compared to 57% at 12 months), time to disease progression (67% compared to 44% at 12 months), and overall survival (78% compared to 65% at 12 months), with no clinically relevant increase in toxicity. Orally administered imatinib is an effective and well-tolerated treatment for patients with CML in accelerated phase. A daily dose of 600 mg is more effective than 400 mg, with similar toxicity.
authors.affiliation: M. D. Anderson Cancer Center, Houston, Texas, USA. mtalpaz@mail.mdanderson.org
authors.forename: Moshe
authors.initials: M
authors.lastname: Talpaz
authors.forename: Richard T
authors.initials: RT
authors.lastname: Silver
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Druker
authors.forename: John M
authors.initials: JM
authors.lastname: Goldman
authors.forename: Carlo
authors.initials: C
authors.lastname: Gambacorti-Passerini
authors.forename: Francois
authors.initials: F
authors.lastname: Guilhot
authors.forename: Charles A
authors.initials: CA
authors.lastname: Schiffer
authors.forename: Thomas
authors.initials: T
authors.lastname: Fischer
authors.forename: Michael W N
authors.initials: MW
authors.lastname: Deininger
authors.forename: Anne L
authors.initials: AL
authors.lastname: Lennard
authors.forename: Andreas
authors.initials: A
authors.lastname: Hochhaus
authors.forename: Oliver G
authors.initials: OG
authors.lastname: Ottmann
authors.forename: Alois
authors.initials: A
authors.lastname: Gratwohl
authors.forename: Michele
authors.initials: M
authors.lastname: Baccarani
authors.forename: Richard
authors.initials: R
authors.lastname: Stone
authors.forename: Sante
authors.initials: S
authors.lastname: Tura
authors.forename: Francois-Xavier
authors.initials: FX
authors.lastname: Mahon
authors.forename: Sofia
authors.initials: S
authors.lastname: Fernandes-Reese
authors.forename: Insa
authors.initials: I
authors.lastname: Gathmann
authors.forename: Renaud
authors.initials: R
authors.lastname: Capdeville
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: Charles L
authors.initials: CL
authors.lastname: Sawyers
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides; D001773:Blood Cells / Q000187:drug effects / Q000473:pathology; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D020732:Cytogenetic Analysis; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D015465:Leukemia, Myeloid, Accelerated Phase / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage* / Q000592:standards / Q000633:toxicity; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000008:administration & dosage* / Q000592:standards / Q000633:toxicity; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases