Title |
Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study
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Published in |
Blood, March 2002
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DOI | 10.1182/blood.v99.6.1928 |
Pubmed ID | |
Authors |
Moshe Talpaz, Richard T. Silver, Brian J. Druker, John M. Goldman, Carlo Gambacorti-Passerini, Francois Guilhot, Charles A. Schiffer, Thomas Fischer, Michael W.N. Deininger, Anne L. Lennard, Andreas Hochhaus, Oliver G. Ottmann, Alois Gratwohl, Michele Baccarani, Richard Stone, Sante Tura, Francois-Xavier Mahon, Sofia Fernandes-Reese, Insa Gathmann, Renaud Capdeville, Hagop M. Kantarjian, Charles L. Sawyers |
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. |
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Geographical breakdown
Country | Count | As % |
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United Kingdom | 2 | 1% |
Austria | 1 | <1% |
Egypt | 1 | <1% |
Denmark | 1 | <1% |
United States | 1 | <1% |
Unknown | 189 | 97% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Master | 29 | 15% |
Researcher | 26 | 13% |
Student > Bachelor | 24 | 12% |
Student > Ph. D. Student | 21 | 11% |
Other | 16 | 8% |
Other | 41 | 21% |
Unknown | 38 | 19% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 71 | 36% |
Agricultural and Biological Sciences | 35 | 18% |
Biochemistry, Genetics and Molecular Biology | 20 | 10% |
Pharmacology, Toxicology and Pharmaceutical Science | 14 | 7% |
Chemistry | 10 | 5% |
Other | 5 | 3% |
Unknown | 40 | 21% |