12 replies to this topic

[kat73]

Depressing news here, and I need advice.  I am now on my fourth pleural effusion and second Sprycel break.  The onc is talking about switching to Bosutinib.  He's willing to start at a reduced dose since I have been at < 0.01% IS for awhile, in an effort to lessen the diarrhea and elevated liver enzymes that are common Bosutinib side effects.  But I am reluctant to move to a new drug, particularly one that's only been around since 2012.  The Phase 3 trial only followed 200-odd patients in the Bosutinib arm.  There have been case studies in which pleural effusions continued under Bosutinib, with PAH developing, to boot.  Although it doesn't target cKIT or PDGFR, it does target the SRC family of kinases, and they could contribute to pleural effusions.  Plus . . . diarrhea!  Need I say more?  Gleevec permanently screwed up my kidney values, but the old liver is doing just fine - why mess with that?

 

What I would like to do is reduce my Sprycel further (I currently am on 50 mg, which obviously didn't keep the pleural effusion away) to 20 mg, plus I'd like to experiment with intermittent dosing.  I'm 66 and have been taking TKI's for 8 years.  I've been MMR or below for 6 years; MR4 (except for the break) for a year or two.  It's going to be a fight; he's a believer in "underdosing" breeds resistance.  But I have a lot of literature and research to cite; I just dread the confrontation.

 

What should I do?  I have some specific questions:  What would be a good starting dose if I did choose the Bosutinib?  If I could persuade him to go down to 20 mg Sprycel, what would be a good intermittent plan?  5 days a week on with the weekends off?  Every other day? One week on, one week off?  And, most importantly, if my PCR continued to be at or below 0.01, would that "prove" there was no resistance developing?

 

Trey and Scuba, especially, but everybody:  please weigh in and help me figure this out.  I'm wondering if I could email Dr. Cortes, since I know he's OK with 20 mg Sprycel for patients, and he worked on Bosutinib.

 

Thanks in advance!

[Buzzm1]

Kat, after a drug break to resolve your 4th pleural effusion, restart Sprycel at 20mg.  It will likely suffice to maintain your BCR-ABL and the probability of a 5th pleural effusion will be that much less.  Before you know it, you'll be feeling like your old self again.   

[thatguy]

I'd be excited at the chance to move away from the p.e's, Kat. Bosulif>Tasigna>Gleevec, in all respects. The diarrhea will likely occur for the first two weeks, and possibly again once or twice. But I've found most of the G.I issues can be overcame with a small meal or more when you take it. The side effects will strengthen if less food is consumed. If you're a normal sized female, I'd think 300MG would be a good place to start, with a tolerable level of side effect, and likely a sufficient dose to control the L. Good luck!

[kat73]

Thanks Buzz and Thatguy.  Thatguy, you cheer me up, thinking of Bosulif as an opportunity instead of a hardship.  I'd still prefer, I think, to take one last shot with 20 mg Sprycel and try an intermittent schedule.

 

Any thoughts on my questions in my post, Trey?  Scuba, should I contact Dr. Cortes for ammo?

[richr]

I had 4 PE's in 8 months and was working on my 5th.  I had them on both gleevec and sprycel.  I ended up having a pleurodesis procedure and have not had a PE since.  Sprycel is really the only TKI for me as when I was on Tasigna I had 2 bouts of pancreatitis. I've been PCRU for a year now and am working with my onc on dose reduction, down to 50mg (though I cheat and take 25 mg one day and 50mg the next).  I want to get to 20mg in hopes that my bone and joint pain will go away. 

 

Good luck with the PEs, not fun getting drained that often.

[kat73]

Thanks, rchr.  I've read about the pleurodesis procedure - kind of alarming concept! - but am glad it's worked for you.  This decision is really weighing on me. 

[cmljax]

Kat. I would fight like hell for dose reduction before switching to a new TKI.  I had to essentially tell my onc that I was reducing from 600mg Tasigna to 450mg back in March because of an uncontrollable skin cancer breakout.  At the time, he mentioned the underdosing leads to resistance argument, but allowed the reduction despite that.  Since then, probably because of my deep and rapid response, my oncologist has permitted 2 more dose reductions (see my signature) in response to other continuing side effects including heart arythmia (benign but quite uncomfortable and unsettling), swollen salivary glands, mouth ulcers and dry mouth. He did not mentioned the underdosing leads to resistance argument on either of these last 2 reductions.  At this time, only mild dry mouth persists for me.

 

The only way to know the minimal therapeutic dose of Sprycel is to keep lowering it and keep testing.  If not 20mg, try 40mg and if you hold your PCR then go to 20mg.  If you maintain on 20mg but continue to get PE's, then it's probably time for a drug switch.  If you do have to switch, you can then at least argue for an equivalent therapeutic dose of the new drug.

[kat73]

Thanks, cmljax, this was clarifying for me!  You're right that you had an amazingly fast and deep response - it was like a descent off a cliff - no wonder your body was rattled.  Certainly you had proof that a lower dose didn't breed resistance.  I am so heartened by your report that you've been able to rid yourself of the most miserable SE's by a low dosage.  My entire goal would be to avoid any more pleural effusions, since I had them on 70 and on 50 mg.  In fact, I would be afraid that if I went back on Sprycel 50 (or whatever the onc said) in order to regain my <0.01 status, that I would immediately start up another pleural effusion.  Do you think it would be reasonable to start back at 20? 

[scuba]

Kat,

 

Absolutely you should consider re-starting Sprycel at 20 mg.

 

There is a very good chance you will remain < 0.01%. It is better to start low and work up given your pleural effusion history.

 

In my own case, I started at 70 mg Sprycel (never full 100 mg) and that lasted one week. I suffered severe myelosuppression (ANC < 0.1) and I had to stop taking Sprycel until my ANC counts recovered. Dr. Cortes restarted me on 20 mg Sprycel. I specifically asked about lowering dose gradually from 70 to 50 and he told me he prefers the opposite and start low and work up. He said sprycel is a very potent drug when it works and that he tends to re-start patients as low as 20 mg and work up as needed. In my case, I responded very well to 20 mg, my ANC counts stabilized and I am currently PCRU. He felt I was able to avoid side effects and at the same time get a terrific response from the drug.

 

You might consider doing the same.

[kat73]

Thanks Scuba.  If I could regain my <0.01 on 20 mg, it would be good data for the argument for staying there, and then I could see if the pleural effusions didn't come back.  Last time it took me only 5 weeks of drug break to slip to 0.02 and by 9 weeks I was at 0.47.  I had to start back up (on 50) while there was still some (minor) residual fluid present.  I was OK for a month, and then the next month I began to feel symptoms again, and the month after that the onc could hear missing sound, far down.  Three months later, chest x-ray showed a moderate pleural effusion (same side.)  This is why I've been feeling a bit "can't win for losin'" lately!  I'm sure I will lose my PCR status on this break, as before - it just doesn't seem to be in the cards for me to go TFR, or at least not yet.  But if I could just sneak back on to the Sprycel track with 20 mg, I'd have a real experiment going:  Will 20 mg be enough to lower my PCR to where it was before or lower?  And, will 20 mg keep the pleural effusions at bay?  If either of those are in the negative, then I'll turn my energies toward tackling the challenge of Bosutinib, and be brave.  Or try.

[Buzzm1]

Kat, looking back at the last time, your drug break was almost 2 and 1/2 months.  

 

http://bit.ly/2pE1pC0

 

No sense testing again until you are ready to restart, to know how much your BCR-ABL has risen.

 

Hoping, like the last time, a quick return to your initial <0.01 is in the cards.

 

This time, without the pleural effusion.

[scuba]

Kat - Also - ask you doctor to reach out to Dr. Cortes about his approach with patients taking sprycel who are < 0.01% and had pleural effusions. It may give your doctor confidence in helping you do the same. 

[kat73]

Thanks, Buzz and Scuba!  I'm reviewing the literature, including Dr. Cortes' summary on pleural effusions, and I'm composing an email to him directly.  I will certainly use his Big Gun in some capacity, Scuba.  And Buzz, my onc wants more PCR's during the break, but I have agreed only to one so far, 4 weeks in.  Seems reasonable, to me. ( I already have a standing appointment with him, in person, in December.)