4 replies to this topic

[Brerose]

Hi everyone,

I have worked my way through Gleevec (could not handle the side effects), Tasigna (liver toxicity) and now Sprycel is circling the drain (also due to liver toxicity). We have tried drug breaks and reduced doses for all 3 drugs and nothing has worked. I don't do any drugs, drink or take any unnecessary medication but my liver is still not a happy camper. Iclusig was my next drug in line but rumor has it that there are some FDA hurdles now with that situation. I am getting nervous knowing how many drugs I have run through considering that I have only been on treatment for one year. I am wondering if there are other people out there that have gone through these three drugs and have still managed to find something that has worked? Without Iclusig, Bosulif seems to me one of my last choices and I have heard that there are potential liver issues there too. If anyone has any advice it would be greatly appreciated.

Thank you,

Bre

[Trey]

There is debate about whether drug induced elevated liver enzymes actually indicate liver toxicity (i.e., damage).  I assume your doc is doing liver function tests.  The problem is that many of these LFT tests are not specific to the liver, but show generalized tissue issues, which can occur with TKI drugs.  So it is often a matter of which LFT tests are out of tolerance, and how far out of tolerance those results are, then viewing the results in light of the side effects of the TKI drugs. 

If your LFT results bounce back quickly after stopping the TKI, then that may also show that this is not so much liver damage as it is drug induced effects, which may or may not be actual liver tissue damage. 

http://www.medicinen...sease/page3.htm

[Brerose]

Thank you for your response and the link Trey. Your comment is very helpful and I appreciate it.

My ALT hovers around 5 times the upper limit of normal. My AST is closer to 3 or 4 times the upper limit of normal. My  bilirubin seems to spike randomly every few weeks at about 3 times the upper limit of normal. I get slight yellowing of my eyes when my bilirubin gets higher. It seems like my ALT and AST dip a bit when my bilirubin spikes and I'm not sure why.

When I held the drug my liver levels dropped quickly. They nearly returned to normal in just two weeks.

Is this a common occurrence that people can get over?  Or is there anything I can do to make my liver stronger?

[hannibellemo]

Brerose,

I'm so sorry you are experiencing this so early in your treatment. I experienced severe liver toxicity 9 months into Gleevec treatment at 400mg. I noticed that my ALT after being very steady increased to 80. My local onc said he would watch it. Three weeks later I mentioned it to my Mayo oncologist when I saw him, he hadn't gotten my CBC/Metabolic panel back at the time of my appointment so he had them run another AST/ALT and do an ultrasound of my liver and those results both came back over 1,000, although the liver looked normal on the ultrasound. I immediately was taken off Gleevec to bring those counts back down and I was off for 7 weeks before they returned to normal. They increased to 1500 ALT/1300AST before dropping. We decided that it was unlikely I would be unable to resume Gleevec without the same results so I switched to Sprycel. I've never had a blip with those enzymes on Sprycel, although I did develop a pleural effusion and my dose was reduced to 50mg. and I've been on that for nearly 18 months with a return to MMR.

During the 7 weeks waiting for my counts to recover I did a lot of searching on the internet for liver toxicity and Gleevec. Though not common it occurs in 3-5% of those taking Gleevec. I came across an Italian study that treated patients with drug induced hepatitis from Gleevec with low dose corticosteroids (25-40mg per day). It was a very small study and I could never convince my docs to give it a try. I was very motivated because I was responding to Gleevec and had relatively few side effects.

http://www.haematolo.../ECR27.full.pdf

I believe their premise for this study was that the liver toxicity was an inflammatory response to Gleevec and could be controlled with short low dose treatment with steroids. My oncs felt that the concern of liver failure and the option of two other drugs, at that time, was a better argument for switching.

I don't know what kind or how severe your side effects were on Gleevec, but because your drug treatment options have dwindled with the concerns over Iclusig and your 3-way translocation, is Gleevec something you would be willing to give another try?

The other thing is, I was told when switching from Gleevec to Sprycel that the same side effects are not necessarily experienced across the board, you may do fine with Bosulif. It is certainly worth the try!

I wish you lots of luck and hope to hear that things are going well for you in the very near future!

Pat

[Brerose]

Thank you Pat for your response. Having access to this blog is priceless, the personal CML stories and wealth of knowledge is pretty incredible. I always end up feeling better after hearing everyone's feedback.

Gleevec was a bit of a nightmare for me but if my options get down to the more serious stuff, I will be willing to try anything. I am grateful that I still have a good response to the tki drugs.

If Sprycel enters my tki graveyard then I will probably end up giving bosulif a shot. Hopefully it will be compatible with my crybaby liver. Considering I didn't drink much at all before my diagnosis and have not had one beer since last October, I am a bit sad my liver is being such a jerk. At least I could have had a little fun to cause these kinds of issues

Thank you both again for your input.

Bre