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

[Lady Lauri]

........  In the Danish Copegus insert it states that one should NEVER break them in half or crush them. It says that if you accidentally touch a crushed pill you should thoroughly wash your skin with soap and water....................

I have heard this before, on not getting the Peg on your skin, etc. but the Riba also? I'm curious on this as we are injecting, ingesting these drugs, why the concern about on our skin?

LL

[Lady Lauri]

Really good work 'up there' Trish. Tx, sides, low hgb and your still rolling in the research, studies, making sense of it all and standing firm with your Dr.'s. Very impressed :)  I have a hard time making sense of it all without much brain fog left!
  I didn't realize you didn't get RVR (just can't keep up here since getting back into the 'real' world, being so busy). Understand your worry on the reduction and standing firm on no more. Glad you got the results you wanted from your last app.
Do take heed on Willys warning, tip. (sure you will, your very studious in all of this)  Not being allowed rescue drugs in my tx was almost a relief for me as I was so concerned about them also. (Course being 2b it's less concern in reduction, etc.)
  
Very nice of your bike group! Be extra careful if your riding thru tx.

Keep up the excellent work and the fight. Rooting for you all the way.

LL

[ladybug52]

I'm so happy that everything worked out so well. Sounds like you and the nurse and the dr are a perfect fit...
I wanted to tell you  that once I had a few shots of procrit my hgb returned to normal and stayed there. I hope the same happens for you.
My dr wanted me to keep taking the procrit but I was worried about the black box warning and quit taking it as soon as possible. If I had to do it over again, I wouldn't have worried about the black box warning so much.
Take care and congratulations on being such a great advocate for your care, especially in a trial!
Bug

[alagirl]

I am really glad for you.  that should work well and give you a little more energy, which is always nice, yeah? ;)

[nerja2007]

heck out this article here http://www.hcvadvocate.org/news/newsLetter/2006/advocate0606.html

[HARRYBEADS]

Harry here, I was put in the same situation for the last 4 months of my treatment and the end results were still negative. Today I went for my post six month blood test, should get results in early August.

Good luck

Harry

[Trish77]

Willy, thanks for the caution on the black box warnings.  I have heard of them and read some and will read some more.  Thanks for your encouragement.  I'm not sure I'll make it with NO problems through 30 more weeks, however this is certainly a good step forward, isn't it.  An interesting approach within the parameters of the trial still and I'm happy.

marcia, thanks for your thoughts. :)

fret, thanks for the vote of confidence my friend and thank you for caring.  That means alot.

Susan - with this approach I get to stay in the trial AND stay within trial parameters.  I'm very happy with that.  I too have to pay for my drugs and that's a bit of a hardship with my son's university expenses at the moment, however I'll take it and work it out.  Good luck to you and I'm hopeful for your upcoming results.

pK .. you give me far too much credit...lol  :)  That goes to the doc.  All I knew going in was that I didn't want dosage reductions and why and that I'm allowed rescue drugs.  I wasn't sure how to pull it all together and wanted to have the discussion with the doc.  I hadn't considered he would give me eprex/procrit before my levels dropped too low.  That was his idea and I was surprised and pleased.   The nurse put me with the most aggressive doctor because she figured that was a good match for my own wishes and bless her for that. Yes, relieved....and having a very decent weekend so far...hope same for you.  :)

Trish

[pKinCA]

Hi Trish,

Wonderful news about your meeting!  All seems to have fallen into place perfectly for you -- in a *trial* no less...  You must have made quite a positive impression on the nurse for her to set you up with thee best doctor!  It really does help to do your homework and come into appointments armed with knowledge and a plan -- for your doctor to follow closely :-)

I'm so glad you don't have to reduce the riba any more than you already have -- I know that thought did not at all sit well with you.  

You must be feeling pretty relieved -- hope you're having a very nice relaxing weekend!

pK

[fretboard]

Sounds like a really good understanding doctor you talked to, at least he has a compromise plan for you that takes what you wanted in the first place and keeps you at a safer place with the addition of epo.  I was wondering how this would end up for you.  I knew you weren't gonna feel comfortable with that riba reduction, so I'm really glad you worked so hard at getting what you wanted and making your viewpoint heard.  Just so you know, I don't know anything at all about epogen.  If you get uncomfortable with that idea, I know you will come up with a back up plan.  God Bless      

[susan400]

Just do what you think is best for you.  If you are comfortable with going outside of your trial for private care and can get the SOC w/rescue drugs, then go that route.  If you're not comfortable with that, then follow the trial guidelines and hope and pray for the best.  That's my advice for what it's worth!

My current trial allows rescue drugs after you've completed the first 29 days w/the study drug (which I now have) and are on SOC.  I told my study nurse on Wed., "I want to do whatever it takes w/all available rescue drugs in order to avoid any dose reductions".  "I told her that with my history of being unable to clear that I am emphatically requesting no dose reductions!"   That's what I did and fortunately for me, it's within the trial guidelines.  I will however have to get those rescue drugs through my private insurance and/or my own pocket.  This is all if I'm even allowed to continue on w/the treatment, because it all depends on my results from my labs that were drawn last Wed. on July 2nd.  If I'm still dropping a steady pace, she told me that they will recommend that I continue on w/treatment.

Susan400

[Willy50]

Good to hear, excellent in fact!!!   It looks like you are going to make it with no problems.

Just a warning...... since the link that you posted came out there have been new warnings on epogen; black label warnings.  The drug is not without it's danger and it is not one that you want overprescribed.  It is to be used as little as possible; just enough to keep you off the reduction list.  This is a drug where less is more.  Just check it out and don't let it be overprescribed or serious and long term problems can develop.  

I'm glad that they checked your iron.  If they get your iron up I think you anemia could improve and almost certainly they won't need as much epogen.

Great to hear this.  It bodes well for your success.

best,
Willy

[Marcia2202]

I am sooooo  happy for you that it worked out this way. Someone above is taking good care of you. Congratulations!!!! Hugs, Marcia

[Trish77]

Well, the really good news and then the really good news.

I called my trial co-ordinator earlier this week, let her know how I felt..that I was okay with 7 days riba reduction and after that, not and certainly no Peg reduction separately or on top of it.  I asked her to let me do the blood test mid week this week as 7 days lands today and results would be back by our appt and then I'd know by today if I could go back to normal dose.  She agreed.  Thank you.  I also let her know I wanted a serious consideration of rescue drugs and where they fit into my picture so that I could avoid future dosage reductions.  She agreed to pass my request on to the doctor and arranged for me to consult with him today.  What I found out TODAY was that she put me with the doc who is known to be the most aggressive on purpose.  Bless her.

So today...my hgb is back above 10 at 10.8.  My whites have rebounded even more that my lymphocytes are .4, still below the .5, however my ANC is at 2.4 which is the best it's been in awhile and far from that 1.5 mark, so the combo again has me avoiding the Peg reduction.   So I am back on regular dosage all around this week.

The REALLY good news is what came out of the consultation with my doctor.  I put my perspective to him that I considered that 7 days riba reduction at this point was tolerable but no more..and that I considered that "as much of the drugs as much of the time" made ALOT of sense to me and that I wanted no further dosage reductions, as much firepower as I could get for as much of the time and if I COULD get it, why wouldn't I.  And I asked him finally.. "does that make sense to you?" and I braced myself for rebuttals and other sorts of things...and his answer was simply .. "Yes."    Just...yes.  

And THEN .. we discussed the rescue drugs.  Well, we discussed the epo.  

The trial parameters say I MUST have a dosage reduction if my limits drop below a certain amount.  So my hep doctor has decided to be proactive with that and keep me OUT of the dosage reduction range by putting me on epo for the duration until my hemoglobin gets above 12.  Because I will have no choice but to dose reduce.. then we make sure I don't have to dose reduce.  I will do weekly epo, weekly blood tests.  So we are being proactive and practicing avoidance of dosage reduction.

I found an article about a study that Dr. Dieterich did supporting the idea of using epo to keep hgb at a level that would avoid ribavirin dosage reductions and it supports this approach.

http://www.natap.org/2001/ddw/ddw_4.htm

If I wasn't in the trial, we could do the epo first and wait out the expected 3 week or so response time.  Because of the trial parameters, I need to keep it from getting below those levels in the first place.

I am VERY happy.  I have a strategy in place to help me avoid dosage reductions, a doctor who listens and is aggressive and uses a proactive approach that is in MY best interests and sits well with what is important to ME in my treatment and will help me both stay in the trial and maintain my dosage to the best of my ability on both counts, both of which are important to me.

Now...my iron is low.  So he is putting me on iron at the same time as the epo as he says the epo will be less effective with my iron at that level.  That has me curious but I'll take it...and will continue to read more about that.  (Nod to Willy)

As for my white levels.. my doc isn't crazy about neupogen, has mixed feelings about it's usefulness and figures the epo will help enough to keep my whites out of reduction range too. I'll cross that bridge IF I get to it.  I'm happy with what I've gotten out of today and I'll just enjoy that very much and go with what I've got and continue to ride it out.

So far so good.  Thankful for a doc who is willing to think outside of the box and what is good for MY big picture.  And thankful for my trial co-ordinator who has put up with me this week, listened to me and let me step through all this and had me see this particular doctor.  

Still might end up with the dosage reductions and that is out of anybody's control.  However, we're all doing everything we can and that's all I really wanted.  I'm at Week 18 today...and moving forward.  Starting epo next week.  

It sounds like a good plan to me.  If any cautions...throw 'em at me.  

Thanks again to *everybody* who tossed things into the pot...I took ALL the big and little pieces into account and it helped me think through this whole thing and educated me enough to know what I felt was best for me.  

A BIG glass of soda water and lime raised to ALL of you!!

Trish

[Trish77]

Thanks for your care.  I'm not letting up.  I'm going after the rescue drugs and I'll be fighting them on dosage reduction.  I got Dr. Dieterich's answer to when dosage reduction is preferred over rescue drugs when rescue drugs are available and he said "never!".  I'm going to do everything I can to stay the course ... and if I get the sense that they are not doing what's best for me when they CAN be doing what's best for me,  THAT is where I'll draw the line on staying in the trial.

Take care and thanks.

Trish

[dointime]

" I have good markers so far .. and I think I can ride it all the way to SVR here. "

Trish, your markers are good but they are not great.  You did not get RVR, so pleeeeeeze don't let up on getting your full dose of drugs and also the rescue drugs that you need.  It's reeeeeally important!  

We who didn't make it to SVR have had a long time to contemplate such things.

dointime  

[Trish77]

Sorry .. you asked about iron a number of times.  I asked the trial co-ord about that and she said they're not monitoring that right now as it's not something they're concerned about. My iron had been on the high side earlier in the trial but not a concerning amount, just a puzzle to her.  She said we would discuss it on Friday if iron was something they need to be looking at.  I'm reading up a bit on creatinin clearance and I'm looking into those trough levels you keep mentioning.  I have the rest of the week til I go to keep reading up and get my information.

I noted Dr. Dieterich's response...that when rescue drugs are available, a dosage reduction is NEVER in order over a rescue drug.  So...I'll have some questions for my team.

Thanks for all your input, Willy...I like a man who can make me think. ;->  And thanks for your support.  Appreciated.

Trish

Trish

[Trish77]

To qualify ...

"I'm convinced my riba dosage is more appropriate at 1200mg.  Not enough evidence out on "true" weight based dosing to settle at 1000mg and plenty of evidence out on the importance of riba in this whole process.  Interesting comprehensive article on all of this.  I found it very good reading:

http://www.natap.org/2007/HCV/100307_03.htm "

There's "true" weight based dosing that applies dosage graduating upwards with weight categories and then standard weight based dosing that goes with 1000mg for <75kg and 1200mg for <75 kg.  

While there's plenty of evidence for weight based dosing vs flat dosing, IMHO not enough studies on the dosages laid out in "true" WBD to bank my dosage on that 1000mg mark and I'll take 1200mg, or higher, thank you very much.

Trish

[Trish77]

I'm going to stick with the trial and ride it out pending further information.  I want them to tell me how the trial data still applies after pulling it at 12 weeks, etc.  I also want them to explain to me why we're not using rescue drugs when it's permitted, so that if an INF reduction comes or this riba reduction continues much longer, I'll know where rescue drugs fit into my picture.  Personally, I"m not against using them on my own if I can get them.  That doesn't contravene the trial.  And I'm thinking on that.

Even if I wasn't sticking with the trial, I can't switch docs and get drugs ordered fast enough to keep things uninterrupted.  It doesn't happen that fast here in Canada, that I know of but haven't ruled it out.  There are a couple of docs I'd be willing to contact if I thought things warranted it, I've left the door open for that a tiny bit but it's very tiny.

I'm convinced my riba dosage is more appropriate at 1200mg.  Not enough evidence out on "true" weight based dosing to settle at 1000mg and plenty of evidence out on the importance of riba in this whole process.  Interesting comprehensive article on all of this.  I found it very good reading:

http://www.natap.org/2007/HCV/100307_03.htm

From everything I've read, due to being UND early on at the 6 week mark and it being past Week 12 at least when the reduction comes, at Week 17, and the reduction being above that 80% mark Willy mentioned, I can tolerate it for 7 days.  I see them on the 7th day.  They will extend until the blood test results come back and I don't get them until after that appointment.  However.  I have a standing order for weekly blood tests and I'm going to go in this week and get my blood test done anyway.  I'll just play dumb and say I thought I was supposed to go in. I get them locally.  It will be there by Friday and we'll all know whether I need to continue with a dosage reduction or not.  They're going to keep it going, so if I have results that show otherwise, I might be able to put a stop to it.  I also run the risk of the whites being low enough for them to order an INF reduction, but I'm ready to deal with that.

Will increase my folic acid and add shiitake lentinin to the mix.. pure lentinin if I can get it, or shiitakes...more is not more with them apparently, so I'll be reading up more on that to get the right "dosage" so to speak.  They are for helping the white counts.  Susan400 has mentioned that in the past and it seems there is data to back that up.

http://www.mskcc.org/mskcc/html/69279.cfm

Ongoing, I"ll take this a step at a time.  I'm committed to the trial, I'm just going to fight a little harder for them to see me as more than a trial number, get more info and do what I can to get my reds and whites up.  I'm almost at Week 24 and then I'll rest easier about these sorts of things.  I still wouldn't want dosage reductions, however they'll be less critical by then, in my opinion.  So I just want to see what I can do to stay the course all around and get there.

There's fighting my own dragon and there's fighting the dragon period.  So I just prefer to stick with the trial and ride it out.  I have good markers so far .. and I think I can ride it all the way to SVR here.

I'm sorry for all the fuss when it could improve and stay that way ... I wasn't expecting the dosage reduction on the ribavirin after staving off the INF reduction every week ... it's clear you can't afford to be complacent about these things and you need to know what you'll do if things do tank, whether a little or a lot.  So now I know.

Will see how it goes.  Thank you much to everybody.

Trish

[Trish77]

Elaine .. just wanted to thank you for your comment and your thoughts.  Someone asked me my perspective and I didn't know yet, other than my perspective was my kids.  

MikeSimon, thanks for your perspective.  I have always appreciated your comments and your perspective is a useful one.  It adds balance.  

LL..thanks for sharing your trial experience and your thoughts.

texas714, thanks for taking the time to comment, I appreciated hearing your thoughts also.

meki ... thanks for being there.

GoofyDad...they'll extend this past 7 days that I feel are the limit, simply due to waiting for blood test results..I'll ask about alternating and see what I can get away with.  Thanks for that.

Thanks all.  

[Trish77]

mremeet, geterdone ... thanks for your input.  Seems very sensible borne out of plenty of experience.  

Teevee..thanks for taking the time to share that.  Your thoughts are appreciated

Kristina...I hadn't heard that about the folic acid interfering with interferon and I'm having a hard time believing that one.  I have two hep doctors, one of which prescribes it at 1mg a day, the other at 5mg a day, saying it's 15-20% chance of it helping with low hemoglobin.  Any actual data on that?  I just read your profile ... I wish you best of luck with your next tround of treatment.

frijole...thanks for your comments.  No real resistance issues with R1626 from what I know.  I tend to agree that higher hgb is better.  I admit I feel like a train running out of steam and it's going to catch up sometime.  This is the last week for both of hte courses I've been doing and I swear I'll be slowing down and really looking forward to that.  I'm concerned about the INF reduction as well, wondering when my time is going to run out on that and hoping it doesn't.. and I'll be talking to them about that when I go on Friday... I have a number of questions I need answers to, to help me make good decisions ongoing.

Willy ... further reading and I find yes...while the concern is that people will think that reducing to 80% of dosage is acceptable, it's more if one MUST reduce, then within 80% of dosage is tolerable, DEPENDING on when one went UND, what week one is in and which drugs, etc. etc.  Most impact is to reduce before Week 12, next before Week 20, more if you are not UND yet and how long you've been UND.  Lesser impact to reduce riba up to 7 days after week 12 and before Week 20, more impact if also reducing INF with riba and more impact reducing INF with no riba reduction in that Week 12 - 20.  Whew.   So .. I have some idea of where I'm at and where it can get to and I'll be glad to get to Week 24.  

[Trish77]

No...not muddying the waters.  That's included in one of the articles I read.  I'll actually be printing that out and bringing it with me when I go to my appointment on Friday.  I need them to explain to me why they're opting for dosage reduction when rescue drugs seem the more prudent choice.  

I'm a firm believer in higher dose riba myself. Nothing I've read in the last day changes my mind a bit about that. To take one less riba each day right now isn't sitting well with me. I know this is my first dosage reduction and it might not go beyond this, it just kills me a bit to use less than full firepower.  If I wasn't in the trial, the issues would be different.  However, I am in the trial, I evaluated that before I went in and now the fire is a little hot and it just makes you think, that's all.

[Marcia2202]

I just wanted to make a comment on breaking Ribavirin into half. In the Danish Copegus insert it states that one should NEVER break them in half or crush them. It says that if you accidentally touch a crushed pill you should thoroughly wash your skin with soap and water.

Marcia

[Proactive]

sounds like you've been reseraching...
google link for ya
http://www.google.com/search?q=10.6+mg+kg+day+of+ribavirin&rls=com.microsoft:en-us&ie=UTF-8&oe=UTF-8&startIndex=&startPage=1

In my mind, the higher the dose of riba toterated the better the chance of svr...period. But each individual will metabolize differently.

Interesting trial of higher dosage...but it ssemd some concensus is already established from prior data.
"Optimal ribavirin dosages are essential in achieving SVR. The initial evidence supporting higher doses of ribavirin for peginterferon alfa-2b comes from a secondary analysis of the pivotal multicenter trial of peginterferon alfa-2b and ribavirin. Patients receiving more than 10.6 mg/kg/day ribavirin experienced significantly higher SVR rates (48% vs. 38%). A large multicenter trial designed to test standard dose ribavirin (1000-1200 mg/day) versus low-dose ribavirin (800 mg/day) in combination with peginterferon alfa-2a, showed 52% SVR in the standard dose group versus 41% in the low-dose group for genotype 1 infected patients. In the pooled data from two pivotal studies with peginterferon alfa-2a and ribavirin, the probability of achieving an SVR for genotype 1 patients was influenced by the ribavirin dose per kg body weight. A 40-50% increase in the probability of SVR was found for a 12-16 mg/kg dose increase of ribavirin. For peginterferon alfa-2b it was also shown among genotype 1 patients, that weight-based ribavirin (800-1400 mg/day) leads to higher SVR rates compared to fixed dose ribavirin (800 mg/day) (34% vs. 29%). Moreover, ribavirin dosing up to 1400 mg/day was safe and the rate of treatment discontinuation was the same for both treatment groups. In a small pilot study, 10 genotype 1 patients with a high baseline load were treated with peginterferon alfa-2a and individualized high-dose ribavirin in order to achieve a ribavirin target concentration in serum of 15 μmol/l. The mean ribavirin dose of 2540 mg/day (range 1600-3600 mg/day) was high, but resulted in 90% SVR. All patients experienced severe anemia, which was treated with concomitant epoetin beta and blood transfusion.

As mentioned before, the main concern of high-dose ribavirin will be a dose-dependent hemolytic anemia and the addition of epoetin alfa has shown significant increase of haemoglobin during (peg)interferon/ribavirin therapy. Erythropoietin doses from 9,000 to 60,000 IU/week have been used in order keep the highest possible ribavirin doses. A recent trial showed a significant higher SVR rate in genotype 1 patients treated with peginterferon alfa-2b, increased dose ribavirin (15.2 mg/kg/day) and epoetin alfa than in patients treated with peginterferon alfa-2b and standard dose ribavirin (13.3 mg/kg/day) with or without epoetin alfa. Using the standard ribavirin dose, routine use of erythropoietin significantly decreased the frequency of anemia and the mean ribavirin dose reduction. Moreover, with the addition of erythropoietin, a significant higher mean dose could be given to patients in the increased ribavirin dose arm."
http://clinicaltrials.gov/ct2/show/record/NCT00662220

and for what it's worth,I'll just toss in..I asked my hep doc point blank...."you must be a very firm believer in higher dose riba, huh?" Answer without hestitation- yes.
(he increased my dosage twice, and a different hep doc in the same gastro/hep dept increased another mh poster's dosage as well--both in response, to slow a slow tx response.

...hope I'm not muddying the waters....;^) Pro

[meki]

We're all here because we belong to an exclusive group Trish --- kinda like our own little "clique"....

We all have been there - knowing what we know now --- and having done what we did then... It makes a world of difference to have been through what we've been through.

It sheds a whole new light on things...

I'm sure cancer forums, etc. All share the same type of bonding.

But one thing is for sure - there is a wealth of information to be shared amongst ourselves that wasn't available 10 years ago.

The internet does provide a LOT of knowledge... And knowledge is POWER.

We are a group of people who can take our experiences and share them with others - so that our knowledge is shared and people can make informed decisions.

But it all bases down to the individual taking all of the information - and then... deciding on their own.

Whatever you decide - we're all here for you.

Meki