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From New options for patients with CML

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New options for patients with CML

Entry of Imatinib (gleevec) has revolutionized the treatment of chronic myeloid leukemia (CML). More are more patients with a diagnosis of CML are now on imatinib (gleevec). Most of these patients do very well on imatinib (gleevec), however some patients never respond to imatinib (gleevec) and some other patients initially respond to this drug but later develop resistance to this drug.

It is estimated that about 10 percent of all patients who initially respond to imatinib (gleevec) subsequently develop resistance to this drug. Now there are new options for those patients who progress on imatinib (gleevec). Mutations in bcr-abl tyrosine kinase may account for the development of resistance to gleevec. Two new drugs dasatinib (drug from Bristol Myers, formerly known as BMS-354825) and AMN107 (drug from Novartis). These new drugs form tighter bonds with the bcr-abl tyrosine kinase target and thus can over come the imatinib resistance caused by bcr-abl tyrosine kinase mutation.

Dasatinib (BMS-354825)
The findings from a phase I study on dasatinib (BMS-354825) were presented in the American Society of Hematology Meeting that was held in December 2004. In that presentation at the plenary session of that meeting, dasatinib was shown to be effective in patients with chronic myeloid leukemia (CML) who have progressed on imatinib. In this study dasatinib was given to patients who were no longer responding to imatinib (gleevec). Eighty six percent of these patients who received this drug achieved complete hematological response in 9 months. Twenty eight percent of patients achieved a major cytogenetic response, more than half of this was complete cytogenetic response. These responses appeared to be durable during the period of study. Further data were presented at the American Society of Clinical Oncology meeting (ASCO) that was held at Orlando in May 2005.

Another phase I study presented at the at the American Society of Clinical Oncology meeting (ASCO) May 2005 focused on patients with blast crisis or accelerated phase of chronic myeloid leukemia (CML). All these patients were either resistant to or intolerant to imatinib (gleevec). The study found that dasatinib (BMS-354825) produced complete hematological response of 50 percent in these patients who had accelerated disease and 28 percent of those who were in blast crisis. These finding are impressive considering the advanced nature of chronic myeloid leukemia (CML) in these patients and that fact that most of these patients were resistant to imatinib (gleevec).

At this time dasatinib (BMS-354825) looks at least as promising as imatinib (gleevec) when it was undergoing phase I trials. Phase II trials and phase III trials have been initiated for dasatinib (BMS-354825) and if the data still holds good this drug may be approved in the near future. Combination of imatinib (gleevec) with dasatinib (BMS-354825) is another area the scientists are eager to explore.

Dasatinib (BMS-354825) is a kinase inhibitor, and is 300 to 1000 times more potent than imatinib (gleevec) for inhibition of bcr-abl tyrosine kinase. Dasatinib is also an SRC inhibitor as well as an abl inhibitor. Dasatinib is orally bio-available and can be taken as an oral pill.

AMN 107
Positive findings from study using AMN107 was recently presented at 96th Annual meeting of American Association of Cancer Research (AACR) that was held in Anaheim, CA. Francis Giles MD and colleagues from MD Anderson Cancer Center in Houston presented this data at the meeting. They evaluated 51 patients on a phase I trial. Of these 51 patients, 36 had accelerated phase chronic myeloid leukemia (CML) and rests of the patients were in blast crisis. The design of the study allowed escalation of dose if the response to AMN 107 is sub optimal. At the time of reporting, responses at lower levels included complete hematological and cytogenetic response responses. Imatinib (gleevec) and AMN 107 have been shown to have synergistic effects and a combination of imatinib (gleevec) and AMN 107 may be more effective than imatinib alone. Clinical trials may be planned to evaluate the efficiency of this combination.

Cancer terms:
Mammogram: This is an X-ray technique for visualization of the soft tissues of the breast. The machine works similar to the X-ray machine used for doing chest X-rays. Breast tumors because of its higher density compared to normal tissues, are seen as abnormalities on a mammogram. Mammogram is able to detect tumors larger than approximately 1-2 mm if calcification is present. If a suspicious spot is identified on a mammogram, your doctor will recommend a biopsy. See section on medical imaging techniques for details. See cancer terms for more cancer related terms. New options for patients with CML

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