Dosage reduction. Cr@p. Impact??

[Trish77]

Well, I finally pushed my luck.  I just got the call.  I've been so obsessed with the damn lymphocytes and whites and it's my reds that got me.  I'm down to 9.6 and they are forcing a ribavirin dosage reduction.  I have to go from 1200mg to 1000mg immediately and indefinitely.  Trial protocol.  Not procrit.  Ribavirin reduction.  My ANC is 1.8 and my lymphocytes are down to .4 .. so no INF reduction because my ANC rebounded enough to offset my lymphocytes.  

Indefinite riba reduction.  I'm very strong about my feelings on the importance of riba.

I don't go for my next blood test until July 4th and they are reducing it until I get the results of that test back  

Today is Week 17.   I was UND by Week 6.

Most of you know I'm on the R1626 trial.   My choice here is to go with the dosage reduction .. or ... not.  Which means dropping the trial.  

I would like to have your feedback on the potential impact of a dosage reduction at this point, for about the two weeks I'm facing right now and potentially longer.  I'm thinking...as long as I can get back to normal after July 4th, I'm good.   Longer than that .. I don't know.

I would appreciate any input, thanks.

The odd thing .. is that I feel pretty good. Not like I'm doing anything overly physical but I'm working fulltime and staying very busy. I'm starting to think I've turned into a tx automaton.  Just keeping on keeping on.

Trish

[pKinCA]

How would you feel about asking Dr. Dieterich for some advice about your situation now?  He might be a good resource...

I'm sorry I don't have much knowledge about riba reduction, but I'm sure the others who do will respond as soon as possible.  (I'm thinking that 1000 mg is still A LOT of riba and it might be plenty to keep the virus at bay, but it's just a guess on my part.  I've "heard" that riba reduction after UND is "okay" but I don't have studies to cite.)

I'm not familiar with your trial drug.  Is it a protease inhibitor?  If yes, that might be a consideration in making your decision.

Cr*p is right!  What a choice to have to make at this point in tx.  You were on such a good roll, handling everything really well !!!  

Good luck Trish...

pK

[Marcia2202]

Sorry to hear the bad news... I cannot comment on your question, as I don't know the answer to it. Just wanted to let you know that I'm praying you will get your SVR regardless... Hugs, Marcia

[Trish77]

To be clear...I have no trial drug anymore.  It stopped at Week 12.  It's a polymerase inhibitor.   To stop the trial drug at Week 12 instead of Week 24 was a potential dosage reduction.  To reduce the riba is another.   In MY eyes, anyway.  Which will have a hard time being objective at the moment, admittedly.

My weight is 160 give or take.  To me, 1200mg was just enough riba. 1000mg is too little.

I don't think it's when you go UND .. .it's how long you've been UND and how far along you are in treatment that matters when the dosage reductions happen.  And that, I don't know...if I managed to get far enough along without the dosage reduction.

Btw.....nice to see you, pK.  :)   I hope you're doing okay..I owe you an email.

Take care and thanks.

Trish

[Trish77]

Thanks Marcia, I appreciate the thought.  I'm sure it'll be okay, I just need some perspective here.

[Lady Lauri]

....dosage reduction ...or....not.......

Are you talking quit, stop tx or jump out of trial and stick with the tx your way?

I would not stop at this point, can you reduce awhile to get the red's up a bit and than ...shhhh.....take that extra pill anyway? I know that is an 'ethical' thing in a trial, but .....you could tell them afterwards???  At a loss here as you were UND by week 6 and would hate to see you stop, do these weeks for 'nothing'.  Trials are tricky as you don't want to change, do extra, not put that data in, etc. Through mine if I took less (on days I thought I was dying, I did a bit less Peg a couple times-NOT a good idea all!!) but I always told them.

Anyhow, I do think it'll be ok with 1000mg, while you'd prefer the 1200mg, it is still a good amount for you.

LL

[Trish77]

Not stopping tx, no.  If I break with trial protocol then my choice, as I understand it, is to leave the trial and find a doc to treat me on SOC out of the trial.

I did tell her I don't NEED to reduce, I'm managing at that hgb level.  That went over like a lead balloon.  She said SHE had no choice therefore neither did I.

Really....I'm not sure how to think on this and I figure the collective wisdom will settle me down or help me think better.

[Willy50]

They have told you all that they can do; their hands are tied so to speak.

Yes, IF you can get your reds back up it may not be a great issue at all.  Your chances of success are quite good based on your 6 week PCR results.  The basic rules are 80% of the drugs at least 80% of the time.  You've scored an early response.  That's the best time to have your RBV up.  IF you can keep the dose up it will help your odds but with each week that goes by it may make incrementally less difference, particularly if your levels are already at recommended levels.

My understanding is that not all people process the RBV the same; your trough levels might be up there and it may not be an issue.  IF they are low however a reduction could be an issue.  You may make certain that you take yours with adequate fat to ensure best rate of absorbtion and compliance.

Understand also that if they are making a correct adjustment of your dosing they are recommending a REDUCTION which could prevent a treatment STOPPAGE of TX.  Just as they have a level which they are forced to reduce the RBV they also have a score which if the patient hits it (yes, no matter how they feel) the treatment ends until the scores improve.  I'm just saying; be careful.  ; )  Stopping is worse than a reduction, no?

There could be another solution; the question is; aside from reducing RBV, is there any other methods of improving ones RBC?  I believe there are.  How is your iron?  If you are pre-menopausal your iron may be low anyway.  For whatever reason many doctors don't check that out before TX even though it is certainly one thing that can be adjusted before treating.  IF your iron is low there are dietary things you can do, and supplemental things as well.  I won't go into that here and now since it may not be the issue.  Even so...... where do you sit with you iron scores?

Just a little "food for thought" for you.  I also wanted to say that I'm pullin for you.

best,
Willy

[mikesimon]

I see no upside in staying in the trial - for you, that is. If you have a doctor who will get you the treatment drugs and any rescue drugs that might become appropriate and order your lab test I would be gone in a heartbeat. That's probably selfish insofar as the trial is concerned but I would want to get well and that would trump the trial. Mike

[Lady Lauri]

That's probably selfish insofar as the trial is concerned but I would want to get well and that would trump the trial. Mike .....

Through out my trial, every reduction, change I'd say "I'm sorry, I'm screwing up your trial"....he'd say....."forget the trial, it's not all about the trial, it's about curing you'!

Nuff said :)

[jmjm530]

Based on what I remember as a robust activity and QOL level for someone on treatment, I'd take a guess that if you were a private patient there would be no reduction in ribavirin and that Procrit (epo) might not be necessary. Unfortunately, trials often do things by the numbers per their protocols and have often have little leeway. Some people can do quite well with hgb in the 9's without a dose reduction and without epo. Others, like myself, needed Procrit when their hgb was in the low 11's.

All the best,

-- Jim

[orleans]

I think it's a little more complex than "the trial". The treatments we now have and take advantage of came about by trials. This is an ethicial question only you can decide. jerry

[Trish77]

"The basic rules are 80% of the drugs at least 80% of the time.  "

Willy, can you please give me more information on where this rule came from and the validity of it, please?   Thank you.

Trish

[Willy50]

Don't throw the baby out with the bath water quite yet.  One minor dose reduction may not make or break this depending upon you RBV trough levels.  They can be checked.  If they are low, then lowering them further is definately a bad move.  If they are UP a relatively minor reduction may not impact them.  Worth a look.

Same deal with your iron.  Where is it?  If you have low iron stores going on Procrit won't help you anyway?  Where is your iron?  Check that too?  IF your iron is low there are pills and there is even iron by IV.  Can they do this testing and augmentation if needed?  Worth asking.

I agree with Mike S. that you could be at a critical point of the trial. Perhaps discussing your concern with them they might be able to take some proactive steps to answer your questions or provide some testing.  That might be better than seeing you walk out on the trial.  I think that many of us in "the states" may also have a simplistic idea of how one gets HCV chemotherapy; it may be different in Canada, eh?

Your goal is to avoid interuptions.  IF you withdrew from the trial today...... you could face a very large interruption in your treatment.  Research and THEN act.

It's slightly off topic..... but are you getting better care with the trial than you might by going to a private physician?  Would your new private physician be up to snuff on the ins and outs of your current Roche trial and subsequent low neuts issues?  IF you were to withdraw from the trial would some aspects of your current low neuts or other issues that could come up be dealt with better by the trial clinic or a new doctor?

I'm great at complicating things.  I'm just saying throughly explore all aspects before jumping.  I know your post is an effort to do this.

I DO agree that your primary reason to treat is to get cured.  I think I also agree that you are still at a critical point in your TX.  Do some research, some shopping and apply a little leverage and charm. ; )

stay in touch.

Willy

[GoofyDad]

You don't mention your weight - which might shed light on the potential impact of the dose reductin. I dropped 200mg toward the end of my tx, and the HGB rose very quickly in response - but I was on a high dose of procrit at the time. You could try reducing by 200 for a while - then do every oher daya for an effective reduction of 100. I bet that would get you back above 10, asssuming that's the magic number....  

[mikesimon]

She's 160 - give or take. Mike

[Trish77]

Willy:  Research and THEN act.
-------------------------------------------------------

Willy, I haven't decided a thing yet .. if you've noticed anything about me you'll know I'm going to think this to *death*.  

Could you give me info on that 80 / 80 rule pls Willy?  would be greatly appreciated.

The other thing here is that this ribavirin reduction came out of the blue.  I didn't expect that.  I've barely been missing the INF reduction week to week.  We've been testing weekly and it's been touch and go.  By rights, my lymphocytes at .4 this week would have been the INF reduction and my ANC at 1.8 instead of 1.5 saved me from that. If they both drop below the magic numbers at the same time, the INF reduces.  How many weeks can I go without them throwing an INF reduction at me too?  I need to think that out too because next they could be saying the INF has to go down too.  And if that comes, I need to know how I'll respond to that.

I have plenty to consider here.  I will reduce my riba by one today to give me time to sort through everything.

and Jerry .... I get that a great deal more than you may think. I'm a pretty serious kinda gal that way. Did not go into the trial lightly, would not leave the trial lightly.

Processing.  And trying to work at the same time....TGIF.

[Texas714]

I think Willy had some good points for you to consider.
You might want to hang in there a bit longer.  Good Luck to you whatever you decide to do.

[willing]

I don't mean to pry into the "give or take" but 160lb is 72.7kg. Per the most recent, large-scale, study that found a significant advantage to weight-based rbv dosing, weight-based was "1000mg for patients weighing 65 to 85Kg".  See Jacobson'07:
http://www.ncbi.nlm.nih.gov/pubmed/17894303

So IMHO it seems that this reduction puts you in line with current weight-based guidelines (I'm kind of surprised they let you do 1200)

Re continuing participation in the trial, there's the  can of worms regarding  whether Roche is  going to go ahead with r1626 given the lymphocyte issue or more aggressively back r7128, which arguably they should have done in the first place - but based on the above there may be no need to open that can.

[Proactive]

Even with a reduction in riba to 1000mg/day, with your body weight of 73 kg's your still getting 13.7 mg/kg/day, well above the minimum 10.6 mg/kg/day I've read is to be considered weight based. As to dropping out of the trial or not, heck, you were pulled off the trial drug, so imo your job as a guinea pig has been fulfilled.

[Willy50]

80/80 is pretty simplistic but it may be considered in your case if only for a week or two while you research.

Hey, my wording wasn't very precise but the general idea is that in HCV treatment there is some room for adjustments and fudge (maybe even hot fudge) ; ) .  100% compliance is not required.  It is a long treatment and many people HAVE to reduce dosages from time to time.  The point is that one week of dose reductions (particularly with RBV that has a longer half life than IFN) may not make or break your treatment.  I feel better that you are at week 17 and not at week 8 and reducing.  

The 80%/80% rule is more like you don't want to really go below those levels as the effectiveness really starts doing a nosedive.  I just want to point out that you may have some flexibility given it is a small reduction and that you are at week 17 and not in the very early stages of TX where compliance may be more vital.  IF you were to graph your current compliance as of yesterday you would be 100% in compliance, no?  That bodes very well for you.  In terms of total dosing one week of a small RBV reduction isn't a grand scale change while you decide what's going on.

It's absolutely a personal choice you must make.  It's also absolutely one that you need to confer with your doctors on.  They may be able to give you some stats on what they think your current chances of SVR are based on comparing to SOC.  They don't have past data on how R1626 works on populations but they may also hazard a best guess with this drug as well.  There really isn't any data so it would really be a guess.  So it goes with my opinion too.  I'm just throwing out a few ideas.

I googled "HCV, 80% dosage, 80% of the time" there are quite a few articles which you can read.  Some were PDF and so I didn't download them but I'd bet you can find quite a few articles.

Here are a few, you can find more by googling the keywords;

http://www.natap.org/2002/Oct/102402_2.h

http://www.medscape.com/viewarticle/503764_7

Keep in mind they pertain to SOC; you've been on triple therapy for 12 weeks.
Keep in mind that dose reductions are of less importance in the later stages of TX
A near RVR will have a lot of weight in your decision.  It's also one reason that I would also agree that it's important to stay proactive and clear this virus THIS TIME.  It sure looks as if it is within your reach.

Yes..... I certainly know you will won't make an impetuous decision.  ; )

best,
Willy

[dointime]

To state the obvious, nobody can say for sure what the impact of a riba dose reduction will be for you, however it has been fairly well determined that weight-based riba is the way to go, so any dose reductions are not ideal.  Having said that, a guy in my trial got reductions in both peg and riba from week 5 right through to the end of his tx and still made SVR.  

So maybe ask yourself this. What if you accept dose reductions because of trial protocol rather than clinical necessity and then you have a breakthrough or a relapse?  You'll never know if you might have SVR'ed but for those dose reductions.  Are you prepared to live with that possible outcome?

Good luck,
dointime  
  

[Willy50]

Given the last posts by willing and Proactive would it be fair to say that even given the dose reduction you will still be above 100% compliance on your RBV dosage?  (maybe you've been doing 120% of what you should have been).  Just another way of thinking about it.  If so you will still be marching ahead doing 100% of both dosages IFN and RBV w/ regard to weight based dosing.  It may not be as bad as was first thought.

Willy

[Trish77]

Willing, thanks for talking kilograms.  

In my head .. (maybe it's a woman thing) my 77kg interprets to me as the "160 pounds, give or take" that my female mind thinks I am.

On the scale at the doc's, I am 77kg.  That's still within your quoted range.

Willing, your reference only goes so far as to say the weight-based range is 800-1400 mg/day.  That is the abstract part at your link.  I'm trying to find the extended details that go with that, seems to quote the WIN-R study.  I'd like to read what dosage goes with what weight.

Anyone...I would like to know the statistics on SVR rates for Geno 1's re-treating.  Will research it, however if someone has them at their fingertips, I'd appreciate it.

Pro..thanks for those numbers..I'll be looking into that closer for better perspective.  As for the trial, they've said they still plan to use the numbers regardless, that the 12 weeks is still relevant.  Remains to be seen, doesn't it.  Guess we'll see the SVR rates based on 12 weeks and go from there.

Willy ... thank you.  For everything.

Not deciding anything, just gathering info.  Really, I should have thought about this harder in the last number of weeks as I could have gotten an INF reduction at any moment. Maybe that's the optimist side of the optimist-realist in me. So anyway, I'm going to think it all through as that is still on the table week to week so I might as well get 'er all done at once, as far as the thinking it out goes.

A quick thanks to everybody who's been tossing their thoughts into the pot, I am most grateful.  

I'll have to set this aside for the moment, as my blue Ninja is an hour away from coming back from her winter sojourn in the back of my buddy's truck, all repaired and ready to ride, thanks to the generosity of the buds in my sportbike group.  Jimmer had a kidney transplant and he's just got the biggest heart. Have to make dinner to say thank you.

Jim...I tend to agree.  If not on the trial, I wouldn't be getting rescue drugs or dosage reduction at this point regardless of the numbers simply due to my own tolerance. I'm thinking I better not slow down...that's the key.  :)

Very grateful, thanks all.

Trish

[willing]

can't trust those things; reminds me of the big "IT LIES" sign on the scale at my Drs office.

Sounds like you've got much better things to attend to, but you should be able to get at the full text by clicking on the "full text ...interscience" icon at the top right of the pubmed page (alternately go to the hepatology journal site and navigate to 2007, vol 46 issue 4).

If that fails (hepatology in the past was not free access) let me know and I can forward the pdf.