43 replies to this topic

[scuba]

Which drug were you thinking on switching to?

[CallMeLucky]

still tossed up on that one, probably Tasigna.  I don't like the idea of going to Sprycel at 100mg.  I don't feel confident in the things I have read that the drug company really knows what the best dosage for Sprycel is yet.  I think it is still evolving and if I was going to make an elective change for side effects, I would not go to it at 100mg.  Of course if I were switching for relapse reasons then I would feel differently.  Since Gleevec has worked pretty well for me, it seems that Tasigna would work that much better, so aside from the inconvenient dosing schedule it seems like on paper it would be the better drug for me.

[pamsouth]

Call Me Lucky,  You do not know how very much I appreciate that post.

I don't remember who your doctor is, but at least she is a very good communicator, and seems to be giving her honest opinion and giving you some real facts!!  Plus you are taking your life style situation in to consideration, that is very smart!!

When my previous onc said the big switch again, we went head to toe.  She gave me no good explanation other then tasigna is better.  Plus when we went over the Bad PCR report, onc even kept saying well there is a lot of room for error on this PCR report, DUH!!, The identical counts on both b2a2 and b3a2,  well even I was not stupid enough to question the validly of the pcr accuracy.  She did do another PCR lab that was only a week apart from that one and it was good!! Not as good as the last 5 1/2 years, but was down from somewhere around a totally of 50 % (from undetectable for 5 1/2 years) to total of 12%.  Their was a slight spike a year ago but the lab had even corrected it as I think they drew from 3 different well and even doc insisted on another PCR and it also came back undetectable. Actually 3 month before that it was a similar situation with the PCR reports up and identical b3a2 and b2a2, they were up too, but FISH AND CBC still great.

Then I called the lab in NJ  where she sends them from Indiana and found out they had changed over to a different numeric scale about a year ago to year 1/2 ago.  So in fact my leukemia cells had not changed at all!!!  I would even say to the doc, hey fish and cbc are great, she would say yea but i will guarantee  you they are going to get bad, but she had been saying that for a year, now!!  So at this point i am believing nothing she says, I have totally lost any and all confidence in her!!!  She has way to many patients for one stand a lone doctor and it would be my guess I am probably may her one and only cml patents, but not sure.  But if you listen to most who see here, it seems she sees a lot of breast cancer patients.

She said all you have do to is go off G for 2 weeks take another EKG before Tasigna and then another EKG two months later and other then that it will be a piece of cake.  One of my question and how often will I have to see you?  Answer just like you do now.  Which is usually every 3 to 4 months. I said back in Feb I had to go to ER with high blood pressure my heart had become irregular and it took me a couple of months to get my heart back to normal.  I told her I had to much stress going on my husband had been sick, my sister grand son and husband had died, my son had been in the hospital 88 days, I didn't need the stress of changing drugs, on top of all that.

Now does she really think that I would not be checking out all the second and third generations?  Does she not think I would be getting a second opinion?  Did she not think I would call the lab and LLS and go out on this board and I have spent several weeks very carefully reading tons of post and asking tons of questions and venting!!  You would think after 6 year she would know me better, and does she stop bugging me no!!

At 64 years old if I am having a fairly good quality of life not great, but I am no spring chicken either.  The G is doing is doing its job.  My insurance is squawking about paying the bills for Gleevec, and the other drugs are even much more expensive, with longer patents.  Now why would I put myself in the unknown and go thru all that, because she says it is a piece of cake?  Now I do my homework, and onc office still calling 3rd week in a row, DR ...... wants to see you again,  and I keep saying, Look i have already talked to her regarding the switch.  I have already done my research and have already said NO.  Driving me crazy!!  So why is she insistent , well I can only guess????

Anyhow when I get the letter from my insurance that they will definitely be paying the bills for the new onc and the labs at his hospital.  I will have test done for probably 9 months to a year with the new onc and if things are not looking good I will certainly reconsider, otherwise I intent to stay on Gleevec.  Now if they prove there is a cure it, (PROVEN CURE) I will jump on it.

Pamsouth

[pamsouth]

Call Me Lucky.  I was thinking the same think if I had to switch it would be the Tasigna!  But aren't you suppose to get the test to find out your mutation and which drugs works best for your particular CMl?

PamSouth

[scuba]

I can only tell you my experience of course ... Sprycel was easy for me to want because it works higher up the pluripotent stem cell chain and there is no issue with dosing schedule. And chances are you won't need full dose.

[Judy2]

Hi Scuba,

What do you mean when you say Sprycel works higher up the pluripotent stem cell chain? It is good to hear Sprycel can still work well at a reduced dose. I will be starting Sprycel at 50mg per day next week and am very nervous about it as I had many side effects on both Tasigna and 300mg Gleevec. 200mg Gleevec did not work well for me. I'm hoping Sprycel at 50 mg per day will do the trick with few side effects, I feel like I'm running out of options.

Judy

[CallMeLucky]

Pamsouth,

I wouldn't need a mutation test at this time because there is no indication I have a mutation.  Gleevec, at the moment, is controlling my CML very well.  If I change, it would be considered an elective change for side effects.  So in my case it seems highly likely that either drug would work for me and since Gleevec has worked so well, Tasigna would likely be a good choice.  I appreciate Michael's point about how Sprycel works, but we also have to acknowledge that there is some lack of understanding on how Sprycel works.  There appears to be an immune system response invoked by Sprycel that is not clearly understood.  So to play devil's advocate, having it effect cells higher up the line, may or may not be a good thing.  We think it is a good thing and it probably is, but I'm not sure and I think we have to realize that we don't know how all this is going to play out.  I don't say that to scare anyone on Sprycel, it appears to be an amazing drug, and I will gladly take in the event I need it, but I don't want to sway my decision on assumptions and correlations.  Sprycel appears to mess with the respiratory system, which is another reason why I shy away from it at the higher dose.  On the other hand Tasigna dosing and heart warnings are certainly something to consider.

[Judy2]

Hi CallMeLucky,

Would you elaborate on the comment about how there seems to be an immune system response invoked by Sprycel?

Just curious as I have an autoimmune condition. Thanks.

Judy

[Tedsey]

Luck,

My doctor is the same way about dosage.  I think there would have to be some very convincing research on lowering dose, and/or I would have to be PCRU for quite a long while before she would change my dosage, (mind you, I am not MMR on Sprycel for 16 months--so, I think it would be crazy for me to reduce dosage).  Although I have complained about pleural effusion, I don't show any outward signs of it.  My hem/onc doubts I have it.  And most people on S don't get it (with two toddlers I so desperately want to see grow up, I couldn't think of putting myself in any danger---drugs aside, the real danger is the disease).

I am a little confused why your onc asked you why you wanted to blow through all your options.  It doesn't seem to make sense.  If you change drugs for lesser side effects or a better response, (despite Gleevec being a seemingly good match for you), and your CML shows signs of continued improvement, or is stable-low (on T or S), why would that mean you are blowing through your options?  I cannot imagine that the leukemia cell works harder to signal other pathways to survive, (the real danger), on T or S because of their different chemical structure.  I think, all in all, anyone would go for the best response with the least amount of side effects.  And CMLers should have this option open to them.  But I can understand your onc thinking along the lines of "if it ain't broke...".  You and I know that none of these drugs "cures" CML.  And luckily big pharma saw it profitable to develop other chemical combos that just so happen to work for many who cannot take G.   For example, there is a chance if you failed Gleevec, (again, God forbid), that you may or may not respond to the "second tier" drugs.  Of course, the odds are that you would, but CML cells can mutate and find other pathways to survival on any of the TKIs. 

So far, Sprycel has been good for me.  It has not brought me miraculously to CMR, (I'm still waiting), and I have low PLT, bad skin, and mouth sores, but I am only assuming these things are side-effects.  The PLT could be the CML (my onc thinks), the bad skin, the pill, and the mouth sores are everyone's guess (probably due to low cell turnover--but that is my unprofessional, influenced by Trey, opinion).  I was not asked to take an EKG for S.  And my onc just monitored me as usual (but I am not far from her office).  She told me to call if I felt anything significant was happening).  I know T is a different story because there is more support for the QT prolongation thing.

Nevertheless, since you can take G, (wish I could--I truly blew through one of my options already), and you are having few issues with it, AND it is cheaper and will go generic first, I would stay.  If it is working and the CML stays low or improves, I would say there is no need to change (not the "ain't broke" philosophy, but "it's effective and the side-effects are relatively tolerable).  But if you did change, I would think it is logical to say you could always go back unless things start to go the other direction on the new drug (or worse side effects).  If your numbers got worse on second drug, then I guess since G is not as strong, it would have happened on G anyway, (for a third time, God forbid).  But in all the non-drug failure scenarios I mentioned, you will not be at risk of "blowing through all your options".  As far as I understand, that only happens when the drugs don't work.  It was not very empathetic for your onc to warn you like this.  I don't think "not fair" is the right word to use in this case.  I think it was kinda manipulative.  But as Trey says, we don't need our onc's all to be Dr Drukers.  Nevertheless, I think we need to feel they are on our side and have our best interest in mind.  And that would probably mean having a good, logical, compassionate, and supported reason to disagree.  If getting the EKG etc. done is not a burden to you, as your onc also serves you and it ultimately will do no harm to anyone, it should not be a burden to her.  She will just be doing her job to follow through regarding her patient's desire or need.  As you said, she does not have to live with CML and its treatment.  But you do.  None of us should be thought of as ignorant children to be tended to.  Many of us choose to be active in and have informed opinions about our treatment.  In this case, we should be considered a respectable partner in the process.  Although it appears she is not very collaborative in nature, it appears you are OK with her.  You are not stupid and you know it (and probably she feels it too, thus, the tension she created).  If she is a tolerable instrument to your good health, then you can hear what she says, entertain it, and go along or not.  If "not" includes searching for a different onc, then so be it.  I guess I don't need to tell you all this.  Just sayin' you have my support.  And what your onc said to you was pretty goofy.  Miffed me a bit.

Good health and long life to you,

Teds        

[tiouki]

Hey CallMeLucky

I totally understand all the issues that would imply switching onc, it would lead to a complicated situation.

But you know, sometimes there is something you want to do but you don't because it is too complicated, too difficult, or would cause a painfull moment. For instance, when you are with someone you don't feel like she/he is the right person for you but it is simple to stay with him/her, or breaking up is just too difficult. Another example is people that are afraid or don't want to get an eye surgery (to correct myopia) but finally they do it and they say "why have I lost that much time I should have done it 10 times ago it's changing my life". Finally you don't regret it.

I don't blame you at all I am having the hardest time myself trying to consider that in my life. Plus there are always a lot of reason/circonstances that make one do nothing it is never that simple. But still I think it is important to keep that in mind.

In your case there are many things that you must consider and I understand your choice. Maybe an alternative solution could be to send an email to Dr Cortes or something (I don't really realize maybe you live 1000 miles from his hospital the US is such a big country ). Anyway I hope you will deal with that and your response to gleevec is really great

That being said I really have to get an appointment to the eye surgeon and break up with my girlfriend (only the first part is true the other one is done and I don't regret it )

Good luck to you !

Cheers

Pierre

[pamsouth]

Call Me Lucky  You hit the nail on the head, at least in my way of thinking when you said "I don't want to sway my decision on assumptions and correlations."

I would like to have the option, as long as Gleevec is working, to see how the history/data collected on these drugs pan out.  Like, yes it is great we even have third generation of TKI drugs in trial.  That is exactly what they are in TRIAL, MEANING THEY DON'T KNOW, MANY THING, NOT ENOUGH TIME AND DATA, that is why it is called TRIAL!!!

Yep new drugs/trial are a good thing if nothing else is working.

But again if Gleevec is doing its job, I just assume wait it out, unless forced to change, because G is working anymore. 

At least Gleevec now  has some data and history.  I have no idea what changing to another drug would have on me, better or worst.  Yea I know there is the option to go back to Gleevec, pros / cons.  Just don't want to upset the apple cart.  But am taking in as much info as my brain will allow.  Sorry if sometimes i am a bit redundant.  Probably won't be on here as much the next few weeks got some others coming up, but at least when I go to my new onc I was have some food for thought.

I hate when doc springs things on you and I am totally in the dark.

PamSouth

[tiouki]

Hello Judy!

I can't remember where I also read this about sprycel. Maybe it is because it also inhibits many kinases (like SRC) which make it that efficient.

I am sure that 50mg sprycel will work well for you. It's quite a reduced dosage (but still much more effective than gleevec), plus sprycel has a different side effect profile than the two other ITKs Good luck !!!

Pierre

[CallMeLucky]

If you Google "dastainib immune" you can find various articles, I recall an interview with Dr. Talpaz where he talked about the "unknown immune response" with dasatinib, but I don't have it readily available.

This is a very interesting article below and after reading it I would swear my doctor wrote it, but she didn't.  I wonder if she read it though as it seems to mirror her position on the issue.

Keep in mind for those of you on second gen TKI or about to switch to second gen TKI, this should not freak you out, they are talking about the minority of patients not the majority, most do very well on second gen TKI, but as someone who is considering an elective change from Gleevec to a second gen TKI, I have to consider these points more carefully.  If I were in a position where I had to switch for disease related reasons, I would not be as concerned about these issues, because I could not control them and chances are they would not happen to me.  My superstitious thinking makes me think if I changed for elective reasons they would likely happen to me

Note - I highlighted the section about Immune response with dasatinib.

http://www.haematolo...96/10/1395.full

Severe adverse events associated with the use of second-line BCR/ABL tyrosine kinase inhibitors: preferential occurrence in patients with comorbidities

1. Peter Valent

+ Author Affiliations

1. Department of Internal Medicine I, Division of Hematology & Hemostaseology, Medical University of Vienna, Austria E-mail: peter.valent@meduniwien.ac.at

Chronic myeloid leukemia (CML) is a hematopoietic neoplasm characterized by uncontrolled myeloproliferation, basophilia, and the BCR/ABL oncoprotein. The natural course of CML includes a chronic phase, an accelerated phase, and a blast phase that resembles an acute leukemia. The BCR/ABL tyrosine-kinase inhibitor (TKI) imatinib is an established standard of therapy in chronic phase CML. However, despite very good long-term results concerning efficacy and safety, resistance against imatinib may occur, often in association with a BCR/ABL mutation.1,2 The treatment of patients with imatinib-resistant CML is a challenge in clinical hematology.3,4 For these patients, two effective second-generation TKI are available: dasatinib and nilotinib.3-6

Recent data suggest that these two TKI, when compared to imatinib, also exert superior anti-leukemic effects in newly diagnosed patients, with higher rates of complete cytogenetic remission and major molecular remission at 12 and 18 months.5,6 Moreover, nilotinib and dasatinib counteract early transformation to blast phase more effectively.5,6 The superior effects of these TKI may result from their strong effects on BCR/ABL (including BCR/ABL-mutants) and their effects on additional drug targets.7 However, such additional targets are also expressed in non-hematopoietic cells and may thus be responsible for non-hematologic adverse events. Whereas side effects are, in many cases, mild and manageable without organ damage, some patients have major problems and develop overt intolerance or even life-threatening adverse events.

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The unique adverse event profile of nilotinib and dasatinib

A unique spectrum of adverse events has been reported for both TKI (Table 1). For dasatinib-treated patients, the occurrence of pleural effusion is a clinical challenge,8-12 especially when pleural effusion is recurrent or accompanied by a perciardial effusion, pulmonary hypertension, or an infection. Several other non-hematologic adverse events have also been described for dasatinib, including diarrhea, skin rash, bleeding, viral re-activation, and sometimes also opportunistic infections which have been reported in patients receiving dasatinib at a dose of 2×70 mg daily (Table 1).11 The frequency of most adverse events appears to be lower when the dose of dasatinib is 100 mg once daily.9 However, even in patients receiving 100 mg once daily, pleural effusions develop and may accumulate over time.12,13

Nilotinib-treated patients may develop increases in pancreatic enzymes, bilirubin, and fasting glucose level (Table 1).5,14,15 Other non-hematologic adverse events include diarrhea, a folliculitis-like skin rash, and bleeding. There are a few reports of severe peripheral arterial occlusive disease (PAOD) and other vascular occlusive events (infarction) in patients receiving nilotinib (Table 1).15,16 Several of these patients developed a rapidly progressive and highly resistant form of PAOD after switching from imatinib to nilotinib.15,16

It is remarkable that pleural effusions rarely occur in nilotinib-treated patients, that severe PAOD has not been reported in patients treated with dasatinib, and that both types of adverse events are rare in imatinib-treated patients.5,6,9,15 Thus, although not confirmed for all types of adverse events in prospective studies, these particular events are considered to be associated with drug-intake, and to occur in a TKI-specific manner. So far, little is known about factors predisposing to the development of such adverse events. From a clinical point of view, this is an essential issue as many patients are candidates for long-term treatment with TKI, or may be transplantable patients in whom comorbidities should be kept to a minimum and should be recognized as early as possible.

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Table 1.  Non-hematologic adverse events and related laboratory abnormalities reported in CML patients treated with dasatinib or nilotinib. 

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Preferential occurrence of severe tyrosine kinase inhibitor-related adverse events in patients who suffer from comorbidities or have other pre-existing risk factors

Recent data suggest that severe TKI-related adverse events (TKI-syndromes) preferentially occur in patients who have pre-existing risk factors or are already suffering from certain comorbidities. For dasatinib-induced pleural effusions, several risk factors such as a pre-existing cardiac disease, arterial hypertension, or auto-immune disorders have been described (Table 2).8-10 Other comorbidities have also been discussed as potential risk factors, but their exact predictive value remains uncertain (Table 2). The impact of comorbidities on effusion-formation in dasatinib-treated patients is confirmed by Breccia et al. in a study published in this issue of the journal.17 They applied two multi-parameter comorbidity scoring systems, the Charlsen comorbidity score and the adult comorbidity evaluation-27 score; according to both scores, comorbidities were found to predict effusion-formation.17 Apart from comorbidities, other risk factors, such as age and the phase of CML, should also be considered in dasatinib-treated patients.8 Finally, the risk of formation of an effusion is clearly higher when the drug is administered at a dose of 2×70 mg per day than at the once-daily 100 mg-dose (Table 2).9,18

Comorbidities that may predispose to the development of PAOD and other vascular occlusive events in nilotinib-treated patients may be the same as those predisposing to PAOD in untreated non-leukemic patients, namely smoking, arterial hypertension, diabetes mellitus, age, and obesity (Table 2).15,16 One or more of these risk factors were identified in almost all CML patients who developed a severe form of PAOD during nilotinib therapy.15,16 It is currently unknown why some of these patients develop a rapidly progressive, severe, treatment-resistant form of PAOD, requiring repeated surgical interventions or even amputation.15,16

An important aspect is that the risk factors predisposing to the development of severe adverse events during treatment with the two TKI may overlap. Thus, age, arterial hypertension, and hypercholesterolemia are risk factors for both pleural effusion-formation during dasatinib treatment and PAOD development in patients taking nilotinib.

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Potential mechanisms and treatment options

The exact mechanisms underlying TKI-induced severe adverse events remain unknown. In the case of dasatinib-induced pleural effusions, a widely discussed hypothesis is that systemic activation of the immune system (by viral reactivation, infections, auto-immune or allergic reactions) is a critical factor.10 In line with this hypothesis, an increase in natural killer cells is often seen in patients with such effusions. Many of these patients also have a skin rash, an allergic episode or a respiratory infection (shortly) before the effusion is diagnosed. In this regard, it is noteworthy that IgE-mediated histamine release from basophils is augmented by low concentrations of dasatinib.19 Moreover, therapy with glucocorticosteroids, known to suppress lymphocyte- and basophil function, exerts beneficial effects in these patients.8,18 From these observations, infections (especially bronchopulmonary infections), auto-immune disorders, and allergic reactions must be taken into account as potentially relevant for the development of effusion-formation in dasatinib-treated patients, and early recognition and management of such comorbidities may be an effective way to prevent effusion-formation. For patients with an overt pleural or pericardial effusion, drug-interruption and dose-reduction, thoracentesis (if needed), short-term glucocorticosteroids, and diuretics are recommended approaches.8,18 In those with repeated severe effusion-formation, it is advisable to discontinue dasatinib and to switch to an alternative drug.

With regard to vascular events, the exact relationship to nilotinib-exposure and the underlying mechanisms remain unclear. Potential explanations include the metabolic effect of nilotinib, direct effects of nilotinib on vascular cells, and drug effects on the coagulation and/or fibrinolytic system. There are several targets of nilotinib that may be involved in these drug-specific effects, including the discoidin domain receptor-1 (DDR1).20 Although imatinib also interacts with DDR1, the suppressive effect of nilotinib on DDR1-activity is much stronger. Whether DDR1 is indeed a critical vascular and pancreatic target of nilotinib is currently under investigation.

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Table 2.  Risk factors and comorbidities predicting specific adverse events in patients treated with second line TKI. 

With regard to therapy and prevention of PAOD, it may be important to treat metabolic and vascular comorbidities and to introduce prophylactic therapy early. An unresolved question is whether a slight increase in the fasting glucose level, which is quite frequently seen in nilotinib-treated patients, should immediately lead to early intervention with anti-diabetic management/therapy. At least repeated testing of glucose levels seems justified. In addition, patients with raised fasting glucose levels should be thoroughly examined for the presence and for the development of PAOD.

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Implications for first-line and second-line therapy

The observations that CML patients who suffer from metabolic, immunological, or vascular comorbidities (often elderly patients) are more likely to develop major non-hematologic adverse events during dasatinib or nilotinib treatment have clinical implications and should assist in patient-selection. In particular, certain comorbidities as well as related risk factors should be taken into account when selecting a second-line TKI. Patients should be examined for the presence and development of risk factors and comorbidities before starting TKI treatment as well as during the therapy. In the case of front-line therapy, it should always be considered that many patients may take TKI for many years or even decades, and that no long-term safety data for dasatinib or nilotinib are available, in contrast to the well-established and superior long-term safety profile of imatinib. It should also be mentioned that predisposing risk factors and comorbidities may develop in most patients with age, even when the factors were not present at the start of therapy. Finally, the safety issues concerning dasatinib and nilotinib are not trivial and the underlying mechanisms are not understood. Many experts do, therefore, consider that, for the time being, imatinib should remain standard front-line therapy in chronic phase CML, at least for patients with Sokal low-risk CML and for older patients suffering from certain comorbidities. In the future this view may change, especially when the mechanisms underlying adverse events are better understood, when studies have shown that the risk can be reduced by appropriate selection of patients and/or comedication, or when CML eradication can be achieved within a relatively short period. A related reasonable concept might be to eradicate most of the more malignant subclones with second- or third-line TKI first, and then switch back to imatinib maintenance therapy at the time of complete molecular remission.

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Summary and future perspectives

Based on the notion that certain comorbidities predispose to the development of severe adverse events in patients receiving dasatinib or nilotinib, front-line and second-line treatment of CML must be adapted to the individual situation in each patient. In many instances the use of such TKI and their superior activity as front-line therapy must be balanced against their potential risk. Even in patients without comorbidities, the risk must be calculated as patients may be treated for many years if not decades and may acquire risk factors over time. Therefore, parameters exploring the risk and detecting TKI-associated adverse events early should be included in the follow up.

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Footnotes

• Dr. Peter Valent is a Group Leader at the Medical University of Vienna, a Coordinator of a CML Working Group in Austria, runs a Center of Excellence and a European Competence Network, and is Scientific Director of the Ludwig Boltzmann Cluster Oncology in Vienna. He has published over 400 peer-reviewed papers and lectured widely in Europe and North America. A major focus of his research is chronic myeloid leukemia and the effects of tyrosine kinase inhibitors.

•    Related Original Article on page 1457
•   Financial and other disclosures provided by the author using the ICMJE (www.icmje.org) Uniform Format for Disclosure of Competing Interests are available with the full text of this paper at www.haematologica.org. 

• Copyright© Ferrata Storti Foundation

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[CallMeLucky]

Pierre - I truly appreciate your analogies, you are funny and pretty wise, especially for your age (if I remember correctly you are on the younger side - so that is a compliment).  You are 100% correct.  As I said before though, this is a marathon and I don't feel the need to make the decision in haste.  If it turns out the only reason I am not making the decision is to avoid the inconvenience, then eventually I will get tired of that and plan for an appropriate time based on work and life schedules.  You know, there is a saying that man makes plans and god laughs! so perhaps looking for the right time is not the best approach either, I remember when my wife and I decided to have a baby, I was unsure of some things at my job and she thought we should wait until it was a better time, I told her we would never have a child if we waited for the "perfect time".  Nonetheless in light of recent issues in my family with my father in law getting ill, it really isn't the best time to rock this apple cart.  Perhaps in a few months or so I will see.  I also feel like as long as my PCR stays negative it is harder to make the choice, if it goes positive again, that would be a strong psychological motivator to switch despite the fact I don't think PCR's are very accurate.

I'm all over the place today.

Tedsey - my doctor did say that I could likely go back to Gleevec if I found the other drugs to be worse, but I she said she can't recall ever switching someone back - of course to me that meant once they switched the majority probably did fine and never looked back,  It is so challenging with doctors they are just people.  Last time I had asked her about switching because of side effects she made a comment that her patients have told her when they switched it was "like getting their life back".

[Judy2]

Hi CallMeLucky,

Thanks for your post. You are right, I have no choice regarding switching so whatever happens happens. Hopefully the reduced Sprycel dose will help eliminate side effects and will work.

CallMeLucky, I think if you get to the point where the side effects become intolerable then your decision regarding switching meds will be easier. As I've said many times I feel quality of life is just as important as quantity, if not more important  For many people the devil you know is better than the devil you don't know but perhaps if you switched there wouldn't be a devil at all. Just a thought. Please keep us posted on what you decide to do.

Judy

[scuba]

Gary - I am glad I switched. I had the nausea, leg cramps and "brain fog" people complained about when I was on Gleevec. It wasn't bad and mostly manageable, but on Sprycel, I have none of that and I have my "life back". But I am on very low dose Sprycel at 20mg. 1/5th the normal level. 

There may be issues with Sprycel and the other new drugs, however. It may work well with knocking CML down faster and deeper, but there is also research that Sprycel may affect other things in the bone marrow negatively (mesenchyme stromal cells for one).

If Gleevec works for you, and you can live with the side affects then you have your solution. As others have said, why mess with what's working for you. Keep in mind that Gleevec has over 10 years of data. Both Trey and Susan are likely cured (they outlived the disease). Gleevec is a solid proven drug.

[pamsouth]

CAll me Lucky,  Thanks for the article.  I skipped thru a lot it.  Didn't understand everything but enough.  That I feel comfortable with my decision with my decision, to stay on Gleevec, which may not fit other's situations.

Yep " Many experts do, therefore, consider that, for the time being, imatinib should remain standard front-line therapy in chronic phase CML, at least for patients with Sokal low-risk CML and for older patients suffering from certain comorbidities."

Article Quote "In the case of front-line therapy, it should always be considered that many patients may take TKI for many years or even decades, and that no long-term safety data for dasatinib or nilotinib are available, in contrast to the well-established and superior long-term safety profile of imatinib. It should also be mentioned that predisposing risk factors and comorbidities may develop in most patients with age, even when the factors were not present at the start of therapy. Finally, the safety issues concerning dasatinib and nilotinib are not trivial and the underlying mechanisms are not understood. Many experts do, therefore, consider that, for the time being, imatinib should remain standard front-line therapy in chronic phase CML, at least for patients with Sokal low-risk CML and for older patients suffering from certain comorbidities. In the future this view may change, especially when the mechanisms underlying adverse events are better understood, when studies have shown that the risk can be reduced by appropriate selection of patients and/or comedication, or when CML eradication can be achieved within a relatively short period. A related reasonable concept might be to eradicate most of the more malignant subclones with second- or third-line TKI first, and then switch back to imatinib maintenance therapy at the time of complete molecular remission.

[Samcerly]

Interesting discussion, as usual you all provide a lot of food for thought!  Just wanted to mention, I have been going for acupuncture every other week or once a month for the past three months to help manage side effects from sprycel.  I take 100mg daily.  Mostly was looking for a reduction in  bone/muscle/joint pain and fatigue.  I can't believe how much it has helped me, my energy is so much better and episodes of leg pain are now few and far between,  hope that helps someone! 

[pamsouth]

Judy, 

that is what I keep thinking for myself, what lucky said;

"For many people the devil you know is better than the devil you don't know but perhaps if you switched there wouldn't be a devil at all. Just a thought." 

That is where I am at, but you have a different situation.

Am praying that Sprycel will work for you, keep us posted! Change is always scary because we just don't know!!

PamSouth

[pamsouth]

Sam, Thinking about that myself.

I have regular massage.  In fact I am taking an intro massage.  Depending on how that goes, I am going to maybe take  some holistic courses as well.  I have a china friend orders all her herbs and patches and stuff sent straight from China.

I think we need to treat the whole person, physical, spiritual, soul. Quality of life is a big issue for me, not just merely existing!

Others seem to have little quality are OK with finding small things in life to bring them happiness. 

I got to have some quality, I can't just, exit, it is like a death sentence for me.

PamSouth