Beth, I'm on SKI606 now called Bosutinib I'm number 21 in Dr Cortes study. i've been on it for a couple years now. i have 300mg at lunch time. i always take it with protein if I don't I will throw it up. I still have skin problem b*ut i have that under control now. i did lose my leg hair and underarm hair. my hair has thined and my euelashes have thin. Irene McAloon * On Wednesday, March 13, 2013 3:56:25 PM UTC-5, Pat wrote:
> Hi all - Dr. Jorge Cortes, one of the world's foremost CML experts, > discusses new treatment options for CML and his thoughts about future > directions in a new article for a physician publication from MD > Anderson Cancer Center which is focused on current research and > patient care advances. > > Regards, > Pat Elliott > CML patient and advocate > > OncoLog, March 2013, Vol. 58, No. 3 > > New Drugs Increase Treatment Options for Patients with Imatinib- > Resistant Chronic Myeloid Leukemia > > By Zach Bohannan > > In the past year, several new targeted drugs have been approved as > second-line treatments for imatinib-resistant chronic myeloid leukemia > (CML). These drugs include the second-generation tyrosine kinase > inhibitor bosutinib and the third-generation tyrosine kinase inhibitor > ponatinib, which may change the standard of care for CML. > > CML treatment > > CML is caused by the BCR-ABL fusion protein, a result of the > Philadelphia chromosomal translocation. The prevalence of this protein > makes CML ideal for treatment using targeted therapies. For many years > now, imatinib, one of the first and most successful targeted > antineoplastic agents, has been the first-line treatment for CML. > “Most CML patients are diagnosed in what we call the chronic phase, > which does not carry any recognizable drug-resistant mutations in BCR- > ABL, so imatinib usually works very well at first,” said Jorge Cortes, > M.D., a professor in the Department of Leukemia at The University of > Texas MD Anderson Cancer Center. > > The main goal of CML treatment is a complete cytogenetic response, > meaning an absence of detectable Philadelphia translocations in the > bone marrow. Many patients treated with imatinib have complete > responses, but the subset of patients who do not are then moved to a > second-line treatment. Thus, there is interest in developing second- > line therapies for imatinib-resistant CML, and several drugs are > currently under investigation or have recently been approved by the > U.S. Food and Drug Administration for this purpose. > > Bosutinib > > Because ABL is a tyrosine kinase, most candidates for second-line CML > treatment are tyrosine kinase inhibitors, which include dasatinib, > bosutinib, and ponatinib. Bosutinib is among the most promising of > these drugs. It is generally considered more potent than imatinib, and > it can overcome several of the mutations that render CML resistant to > imatinib. > > The side effects of bosutinib are less severe—and most are less common— > than those of some other tyrosine kinase inhibitors because bosutinib > has less effect on the development of normal blood cells. For example, > nilotinib, dasatinib, and several other tyrosine kinase inhibitors > also inhibit growth factor receptors such as c-KIT and platelet- > derived growth factor receptor. These receptors are important for the > normal development of certain myeloid cell types. Bosutinib, however, > does not affect these receptors as strongly as many other tyrosine > kinase inhibitors and thus causes lower rates of neutropenia and > thrombocytopenia than do nilotinib and dasatinib. Similarly, bosutinib > causes lower rates of cardiotoxicity and pancreatitis than other > second-generation tyrosine kinase inhibitors that are approved for > treating imatinib-resistant CML. Conversely, some side effects might > be more common with bosutinib. > > This lack of significant side effects is one reason bosutinib is so > attractive. However, Dr. Cortes said, “Although all tyrosine kinase > inhibitors are very safe compared with most other chemotherapies, > there can still be adverse events, and doctors should explain and > discuss possible side effects with patients.” The primary side effect > associated with bosutinib is diarrhea, which can occur in up to 80% of > patients. However, this is usually minor and manageable. > > Although bosutinib is superior to many other possible treatments for > CML, it is not effective for all patients. For example, the T315I > point mutation that can occur in the BCR-ABL gene renders CML > resistant to imatinib, bosutinib, and most other tyrosine kinase > inhibitors. > > Ponatinib > > Ponatinib is a very potent tyrosine kinase inhibitor that was > specifically designed to treat the T315I point mutation while > maintaining efficacy against all other known BCR-ABL permutations. > Although ponatinib has many of the same side effects as other tyrosine > kinase inhibitors, its ability to treat a previously intractable > mutation makes it very promising. Because it is very effective against > T315I-mutated BCR-ABL and in patients who have not responded to > multiple other tyrosine kinase inhibitors, ponatinib was recently > approved as a second-line treatment for CML patients. > > New first-line therapy? > > Stem cell transplant: offers curative potential but with greater risks > compared to therapy with tyrosine kinase inhibitors; seldom used as > initial therapy but considered for patients who have not responded > well to other therapies. > > Because bosutinib shows so many benefits over other tyrosine kinase > inhibitors, Dr. Cortes conducted some preliminary research into its > use as a first-line therapy for CML. The initial research set out to > determine whether bosutinib would offer a better cytogenetic and > molecular response rate than imatinib. Dr. Cortes said, “We found that > bosutinib and imatinib have similar cytogenetic response rates, so the > primary endpoint of the study was inconclusive. However, in many of > the other measures examined, such as the number of adverse events, > bosutinib was superior.” > > Another notable finding of that study was that bosutinib caused a > complete cytogenetic response faster than imatinib did. Many studies > have shown that speed of response has a major effect on long-term > survival for CML patients. However, much more research, some of which > is ongoing, will be needed before bosutinib can be recommended or > officially adopted as the gold standard for CML treatment. > > Ponatinib also is being studied as a first-line treatment. In an > ongoing phase II clinical trial, Dr. Cortes and his colleagues are > evaluating the drug’s effectiveness in patients with previously > untreated chronic-phase CML. Laboratory data suggesting that it is > difficult to induce ponatinib resistance makes ponatinib an attractive > treatment option that could reduce the probability of acquiring > resistance and thus improve the long-term outcome. > > Future directions and challenges > > CML patients require frequent monitoring to ensure their disease does > not recur, and many patients remain in fear that their CML will return > with a mutation that renders it resistant to currently available > treatments. However, the recent approval of ponatinib and omacetaxine > (a translation inhibitor also found to be active against CML) means > that 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 > determine whether a patient has been cured. Patients who achieve a > complete cytogenetic response may undergo more sensitive molecular > testing. A complete molecular response, defined as the absence of > detectable BCR-ABL transcripts, is the best possible outcome a > physician can assess for a CML patient, but there is still no way of > knowing if the CML has been completely eliminated because even > molecular tests have a limit of detection. “To completely cure CML, we > need to develop other therapeutic options and better testing for > residual disease,” Dr. Cortes said. “Right now, the best I can tell > patients 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, > tyrosine kinase inhibitors will probably need to be combined with > another therapy to cure CML patients. The most likely therapy to > combine with tyrosine kinase inhibition is stem cell transplantation. > > However, until more powerful tests are developed, doctors will > continue to treat CML as a chronic disease, which means that many > patients will receive life-long targeted therapy, whether it is > imatinib or sequential treatment with multiple tyrosine kinase > inhibitors as the disease mutates. > > Current Treatments for Chronic Myeloid Leukemia > > Imatinib: tyrosine kinase inhibitor approved by the U.S. Food and Drug > Administration as a first-line treatment for chronic myeloid leukemia > (CML); often successful > > Dasatinib: second-line tyrosine kinase inhibitor for some imatinib- > resistant mutants > > Bosutinib: second-line tyrosine kinase inhibitor for some imatinib- > resistant mutants > > Nilotinib: second-line tyrosine kinase inhibitor; slightly modified > version of imatinib > > Omacetaxine: alkaloid translation inhibitor for treating T315I-mutant > CML > > Ponatinib: second- or third-line tyrosine kinase inhibitor for > treating T315I-mutant CML > > Stem cell transplant: offers curative potential but with greater risks > compared to therapy with tyrosine kinase inhibitors; seldom used as > initial therapy but considered for patients who have not responded > well to other therapies. > > Article link: > http://www2.mdanderson.org/depts/oncolog/articles/13/3-mar/3-13-2.html > -- -- [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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