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| Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the philadelphia chromosome. |
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| Author(s): Druker BJ, Sawyers CL, Kantarjian H, Resta DJ, Reese SF, Ford JM, Capdeville R, Talpaz M |
| Source: NEW ENGLAND JOURNAL OF MEDICINE Volume: 344 Issue: 14 Pages: 1038-1042 Published: APR 5 2001 |
| Times Cited: 1,335 References: 20 |
| Abstract: Background: BCR-ABL, a constitutively activated tyrosine kinase, is the product of the Philadelphia (Ph) chromosome. This enzyme is present in virtually all cases of chronic myeloid leukemia (CML) throughout the course of the disease, and in 20 percent of cases of acute lymphoblastic leukemia (ALL). On the basis of the substantial activity of the inhibitor in patients in the chronic phase, we evaluated STI571 (formerly known as CGP 57148B), a specific inhibitor of the BCR-ABL tyrosine kinase, in patients who had CML in blast crisis and in patients with Ph-chromosome-positive ALL. Methods: In this dose-escalating pilot study, 58 patients were treated with STI571; 38 patients had myeloid blast crisis and 20 had ALL or lymphoid blast crisis. Treatment was given orally at daily doses ranging from 300 to 1000 mg.
Results: Responses occurred in 21 of 38 patients (55 percent) with a myeloid-blast-crisis phenotype; 4 of these 21 patients had a complete hematologic response. Of 20 patients with lymphoid blast crisis or ALL, 14 (70 percent) had a response, including 4 who had complete responses. Seven patients with myeloid blast crisis continue to receive treatment and remain in remission from 101 to 349 days after starting the treatment. All but one patient with lymphoid blast crisis or ALL has relapsed. The most frequent adverse effects were nausea, vomiting, edema, thrombocytopenia, and neutropenia.
Conclusions: The BCR-ABL tyrosine kinase inhibitor STI571 is well tolerated and has substantial activity in the blast crises of CML and in Ph-chromosome-positive ALL. (N Engl J Med 2001;344:1038-42.) Copyright (C) 2001 Massachusetts Medical Society.
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| Document Type: Article |
| Language: English |
| Reprint Address: Druker, BJ (reprint author), Oregon Hlth Sci Univ, Div Hematol & Med Oncol, L592,3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA |
Addresses:
1. Oregon Hlth Sci Univ, Div Hematol & Med Oncol, Portland, OR 97201 USA
2. Univ Calif Los Angeles, Div Hematol & Oncol, Los Angeles, CA USA
3. Univ Texas, MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA
4. Univ Texas, MD Anderson Canc Ctr, Dept Bioimmunotherapy, Houston, TX 77030 USA
5. Nova Pharmaceut Corp, Dept Oncol Clin Res, E Hanover, NJ USA
6. Nova Pharmaceut Corp, Dept Oncol Clin Res, Basel, Switzerland |
| Publisher: MASSACHUSETTS MEDICAL SOC, WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA |
| Subject Category: Medicine, General & Internal |
| IDS Number: 417XH |
| ISSN: 0028-4793 |
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