thank you Pat, for sharing this article. Very informative. As I am now on Bosutinib, week six and advancing dose slowly, I am wondering if anyone else out there is currently using this drug and if so, what is your experience, side effects etc......Beth
-----Original Message----- From: Pat <pfemail...@gmail.com> To: CMLHope <cmlhope@googlegroups.com> Sent: Wed, Mar 13, 2013 3:56 pm Subject: [CMLHope] Update on CML Treatments Hi all - Dr. Jorge Cortes, one of the world's foremost CML experts, iscusses new treatment options for CML and his thoughts about future irections in a new article for a physician publication from MD nderson Cancer Center which is focused on current research and atient care advances. Regards, at Elliott ML patient and advocate OncoLog, March 2013, Vol. 58, No. 3 New Drugs Increase Treatment Options for Patients with Imatinib- esistant Chronic Myeloid Leukemia By Zach Bohannan In the past year, several new targeted drugs have been approved as econd-line treatments for imatinib-resistant chronic myeloid leukemia CML). These drugs include the second-generation tyrosine kinase nhibitor bosutinib and the third-generation tyrosine kinase inhibitor onatinib, which may change the standard of care for CML. CML treatment CML is caused by the BCR-ABL fusion protein, a result of the hiladelphia chromosomal translocation. The prevalence of this protein akes CML ideal for treatment using targeted therapies. For many years ow, imatinib, one of the first and most successful targeted ntineoplastic agents, has been the first-line treatment for CML. Most CML patients are diagnosed in what we call the chronic phase, hich does not carry any recognizable drug-resistant mutations in BCR- BL, so imatinib usually works very well at first,” said Jorge Cortes, .D., a professor in the Department of Leukemia at The University of exas MD Anderson Cancer Center. The main goal of CML treatment is a complete cytogenetic response, eaning an absence of detectable Philadelphia translocations in the one marrow. Many patients treated with imatinib have complete esponses, but the subset of patients who do not are then moved to a econd-line treatment. Thus, there is interest in developing second- ine therapies for imatinib-resistant CML, and several drugs are urrently under investigation or have recently been approved by the .S. Food and Drug Administration for this purpose. Bosutinib Because ABL is a tyrosine kinase, most candidates for second-line CML reatment are tyrosine kinase inhibitors, which include dasatinib, osutinib, and ponatinib. Bosutinib is among the most promising of hese drugs. It is generally considered more potent than imatinib, and t can overcome several of the mutations that render CML resistant to matinib. The side effects of bosutinib are less severe—and most are less common— han those of some other tyrosine kinase inhibitors because bosutinib as less effect on the development of normal blood cells. For example, ilotinib, dasatinib, and several other tyrosine kinase inhibitors lso inhibit growth factor receptors such as c-KIT and platelet- erived growth factor receptor. These receptors are important for the ormal development of certain myeloid cell types. Bosutinib, however, oes not affect these receptors as strongly as many other tyrosine inase inhibitors and thus causes lower rates of neutropenia and hrombocytopenia than do nilotinib and dasatinib. Similarly, bosutinib auses lower rates of cardiotoxicity and pancreatitis than other econd-generation tyrosine kinase inhibitors that are approved for reating imatinib-resistant CML. Conversely, some side effects might e more common with bosutinib. This lack of significant side effects is one reason bosutinib is so ttractive. However, Dr. Cortes said, “Although all tyrosine kinase nhibitors are very safe compared with most other chemotherapies, here can still be adverse events, and doctors should explain and iscuss possible side effects with patients.” The primary side effect ssociated with bosutinib is diarrhea, which can occur in up to 80% of atients. However, this is usually minor and manageable. Although bosutinib is superior to many other possible treatments for ML, it is not effective for all patients. For example, the T315I oint mutation that can occur in the BCR-ABL gene renders CML esistant to imatinib, bosutinib, and most other tyrosine kinase nhibitors. Ponatinib Ponatinib is a very potent tyrosine kinase inhibitor that was pecifically designed to treat the T315I point mutation while aintaining efficacy against all other known BCR-ABL permutations. lthough ponatinib has many of the same side effects as other tyrosine inase inhibitors, its ability to treat a previously intractable utation makes it very promising. Because it is very effective against 315I-mutated BCR-ABL and in patients who have not responded to ultiple other tyrosine kinase inhibitors, ponatinib was recently pproved as a second-line treatment for CML patients. New first-line therapy? Stem cell transplant: offers curative potential but with greater risks ompared to therapy with tyrosine kinase inhibitors; seldom used as nitial therapy but considered for patients who have not responded ell to other therapies. Because bosutinib shows so many benefits over other tyrosine kinase nhibitors, Dr. Cortes conducted some preliminary research into its se as a first-line therapy for CML. The initial research set out to etermine whether bosutinib would offer a better cytogenetic and olecular response rate than imatinib. Dr. Cortes said, “We found that osutinib and imatinib have similar cytogenetic response rates, so the rimary endpoint of the study was inconclusive. However, in many of he other measures examined, such as the number of adverse events, osutinib was superior.” Another notable finding of that study was that bosutinib caused a omplete cytogenetic response faster than imatinib did. Many studies ave shown that speed of response has a major effect on long-term urvival for CML patients. However, much more research, some of which s ongoing, will be needed before bosutinib can be recommended or fficially adopted as the gold standard for CML treatment. Ponatinib also is being studied as a first-line treatment. In an ngoing phase II clinical trial, Dr. Cortes and his colleagues are valuating the drug’s effectiveness in patients with previously ntreated chronic-phase CML. Laboratory data suggesting that it is ifficult to induce ponatinib resistance makes ponatinib an attractive reatment option that could reduce the probability of acquiring esistance and thus improve the long-term outcome. Future directions and challenges CML patients require frequent monitoring to ensure their disease does ot recur, and many patients remain in fear that their CML will return ith a mutation that renders it resistant to currently available reatments. However, the recent approval of ponatinib and omacetaxine a translation inhibitor also found to be active against CML) means hat these mutations may prove to be less of a threat in the future. One problem inherent in any CML treatment is that there is no way to etermine whether a patient has been cured. Patients who achieve a omplete cytogenetic response may undergo more sensitive molecular esting. A complete molecular response, defined as the absence of etectable BCR-ABL transcripts, is the best possible outcome a hysician can assess for a CML patient, but there is still no way of nowing if the CML has been completely eliminated because even olecular tests have a limit of detection. “To completely cure CML, we eed to develop other therapeutic options and better testing for esidual disease,” Dr. Cortes said. “Right now, the best I can tell atients is, ‘I don’t see it (the leukemia),’ which is different from, It’s gone.’” He believes that once a more powerful test is developed, yrosine kinase inhibitors will probably need to be combined with nother therapy to cure CML patients. The most likely therapy to ombine with tyrosine kinase inhibition is stem cell transplantation. However, until more powerful tests are developed, doctors will ontinue to treat CML as a chronic disease, which means that many atients will receive life-long targeted therapy, whether it is matinib or sequential treatment with multiple tyrosine kinase nhibitors as the disease mutates. Current Treatments for Chronic Myeloid Leukemia Imatinib: tyrosine kinase inhibitor approved by the U.S. Food and Drug dministration as a first-line treatment for chronic myeloid leukemia CML); often successful Dasatinib: second-line tyrosine kinase inhibitor for some imatinib- esistant mutants Bosutinib: second-line tyrosine kinase inhibitor for some imatinib- esistant mutants Nilotinib: second-line tyrosine kinase inhibitor; slightly modified ersion of imatinib Omacetaxine: alkaloid translation inhibitor for treating T315I-mutant ML Ponatinib: second- or third-line tyrosine kinase inhibitor for reating T315I-mutant CML Stem cell transplant: offers curative potential but with greater risks ompared to therapy with tyrosine kinase inhibitors; seldom used as nitial therapy but considered for patients who have not responded ell to other therapies. Article link: http://www2.mdanderson.org/depts/oncolog/articles/13/3-mar/3-13-2.html -- - CMLHope] support group of http://cmlhope.com ------------------------------------------------ You received this message because you are subscribed to the Google Groups CMLHope" group. o post to this group, send email to CMLHope@googlegroups.com o unsubscribe from this group, send email to cmlhope-unsubscr...@googlegroups.com or more options, visit this group at http://groups.google.com/group/CMLHope -- ou received this message because you are subscribed to the Google Groups CMLHope" group. o unsubscribe from this group and stop receiving emails from it, send an email o cmlhope+unsubscr...@googlegroups.com. or more options, visit https://groups.google.com/groups/opt_out. -- -- [CMLHope] A support group of http://cmlhope.com ------------------------------------------------- You received this message because you are subscribed to the Google Groups "CMLHope" group. 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