| Imatinib produces significantly superior molecular responses compared to interferon alfa plus cytarabine in patients with newly diagnosed chronic myeloid leukemia in chronic phase. | |
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MedLine Citation:
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PMID: 14523461 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We analyzed molecular responses in 55 newly diagnosed chronic-phase chronic myeloid leukemia (CML) patients enrolled in a phase 3 study (the IRIS trial) comparing imatinib to interferon-alfa plus cytarabine (IFN+AraC). BCR-ABL/BCR% levels were measured by real-time quantitative RT-PCR and were significantly lower for the imatinib-treated patients at all time points up to 18 months, P<0.0001. The median levels for imatinib-treated patients continued to decrease and had not reached a plateau by 24 months. A total of 24 IFN+AraC-treated patients crossed over to imatinib. Once imatinib commenced, the median BCR-ABL/BCR% levels in these patients were not significantly different to those on first-line imatinib for the equivalent number of months. The incidence of progression in imatinib-treated patients, defined by hematologic, cytogenetic or quantitative PCR criteria, was significantly higher in the patients who failed to achieve a 1 log reduction by 3 months or a 2 log reduction by 6 months, P=0.002. A total of 49 patients were screened for BCR-ABL kinase domain mutations. Mutations were detected in two imatinib-treated patients who crossed over from IFN+AraC and both lost their imatinib response. In conclusion, first-line imatinib-treated patients had profound reductions in BCR-ABL/BCR%, which significantly exceeded those of IFN+AraC-treated patients and early measurements were predictive of subsequent response. |
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Authors:
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S Branford; Z Rudzki; A Harper; A Grigg; K Taylor; S Durrant; C Arthur; P Browett; A P Schwarer; D Ma; J F Seymour; K Bradstock; D Joske; K Lynch; I Gathmann; T P Hughes |
Publication Detail:
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Type: Clinical Trial; Clinical Trial, Phase III; Comparative Study; Journal Article; Randomized Controlled Trial |
Journal Detail:
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Title: Leukemia Volume: 17 ISSN: 0887-6924 ISO Abbreviation: Leukemia Publication Date: 2003 Dec |
Date Detail:
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Created Date: 2003-12-12 Completed Date: 2004-01-23 Revised Date: 2013-03-04 |
Medline Journal Info:
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Nlm Unique ID: 8704895 Medline TA: Leukemia Country: England |
Other Details:
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Languages: eng Pagination: 2401-9 Citation Subset: IM |
Affiliation:
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Institute of Medical and Veterinary Science, Adelaide, South Australia. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antimetabolites, Antineoplastic
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administration & dosage* Antineoplastic Agents / administration & dosage* Bone Marrow / metabolism Cross-Over Studies Cytarabine / administration & dosage* Cytogenetics DNA Mutational Analysis Fusion Proteins, bcr-abl / blood, chemistry, genetics Humans Interferon-alpha / administration & dosage* Leukemia, Myelogenous, Chronic, BCR-ABL Positive / diagnosis, drug therapy*, genetics Phosphotransferases / chemistry, genetics Piperazines / administration & dosage* Prognosis Protein Structure, Tertiary Pyrimidines / administration & dosage* Treatment Outcome |
| Chemical | |
Reg. No./Substance:
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0/Antimetabolites, Antineoplastic; 0/Antineoplastic Agents; 0/Fusion Proteins, bcr-abl; 0/Interferon-alpha; 0/Piperazines; 0/Pyrimidines; 147-94-4/Cytarabine; BKJ8M8G5HI/imatinib; EC 2.7.-/Phosphotransferases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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