Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study.
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.
Talpaz
Moshe
M
M. D. Anderson Cancer Center, Houston, Texas, USA. mtalpaz@mail.mdanderson.org
Silver
Richard T
RT
Druker
Brian J
BJ
Goldman
John M
JM
Gambacorti-Passerini
Carlo
C
Guilhot
Francois
F
Schiffer
Charles A
CA
Fischer
Thomas
T
Deininger
Michael W N
MW
Lennard
Anne L
AL
Hochhaus
Andreas
A
Ottmann
Oliver G
OG
Gratwohl
Alois
A
Baccarani
Michele
M
Stone
Richard
R
Tura
Sante
S
Mahon
Francois-Xavier
FX
Fernandes-Reese
Sofia
S
Gathmann
Insa
I
Capdeville
Renaud
R
Kantarjian
Hagop M
HM
Sawyers
Charles L
CL
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
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases