Double dose interferon

How many weeks do people usually DD if that's the path that they are to take?

[Myown]

I'm talking about beginning of tx ,,,,,4 weeks?

[CockSparrow]

Until you are UND. No point doing it for longer.
So basically this would work out to be 4-8 weeks for G2s/3s.
Because you cant get the results of a 4 week PCR all that quickly, I would keep DD until you have the results.

CS

[sfbaygirl]

Sounds right to me!  Get that UND, maybe it will only be in 2 weeks! Don't do both shots at once, I would do mid weeks.  Good luck with it!  That is what I would do too!..

Linda

[mikesimon]

Since you reached undetectable at 4 weeks with standard dose interferon I wonder how this is relevant to your situation - particularly if you would stop the double dosing at the point that you are undetectable. I thought the Peg double dosing approach was aimed at treating those people who didn't reach RVR and/or EVR. You did so I am again perplexed by this question - but it sure isn't the first time. Mike

[jmjm530]

In general, I have to agree with Mike and point out again the purpose of tx is to kill the virus and not the patient. That said, if you don't mind taking what some might consider unreasonable risks given your histology and prior RVR, then double-dosing in theory could hasten your RVR -- in other words getting you to UND in let's say 3 instead of 4 weeks which in spite of no study data, one could reasonably argue would give you a better chance of SVR.

This, of course, would require weekly testing, which I believe you had before? But again, I doubt this is the problem and what seems to be the answer is longer (48 weeks) of tx this time around and perhaps with a different Peg --  i.e. Peg Intron if last time you used Peagasys -- although one could reasonably argue to stay with the same Peg since it brought you RVR last time.

Curious, exactly what was your new doctor's original recommended tx program  in  terms of dosage and tx length? Also, how much of your input  -- Alinia, etc -- is being added to that recommendation or is it still a work in progress?

-- Jim

[nygirl7]

You'd  be better off upping the riba if anything - it's my understanding that double dosing peg won't do much to you as a previous RVR except kill your thyroid and cause all sort of hellish autoimmune problems.

You can't just start doubling up on meds out of nowhere and add things on as if it was a game or you can expect pretty big problems.

I would seriously rethink the double dosing peg -you need more time and more riba.  Do the SOC of 48 weeks and maybe add one 200 to weight based but leave the peg along. As an RVR it's just not what you need at all.

[Myown]

Remember the 6 months of interferon I just received? Well guess what? The boxes say 360mcg every week on it. I didn't realize that - who would think to look cause I was RVR last time. But my doctor says my immune system stinks being it came back and maybe thats why he wants to do this - who knows.

But anyhow,I called the pharma and he said the script that he received from the doctor was 360 for 3 MONTHS....I said , well that is news to me, cause he never told me that.

I emailed doc and told him and said I would call him today or tomorrow. I couldn't call him in the morning cause (get ready for this one) I had to go over NYC to my ENT cause he has the Cat Scan that I just had done to see if he sees anything.....got over there and winds up the guy didn't scan the part that he wanted scanned!! I'm still trying to get over that one. Ticked off, not that it was the doctors fault.  

Jim. Alinia through out treatment and I asked if I can taper down interferon at the end and continue Alinia for 3 months,,,he said yes to it all.

[Myown]

Yeah so, maybe the script is a mistake, but maybe not.

[nygirl7]

So therefore you are going to be double dosing on peg at 360 = that makes no sense to double the meds and the chance at reactions (especially in light of your GI issues) and do half the time.  You should seriously get a second with Dr. J.

[jmjm530]

MO: But my doctor says my immune system stinks being it came back and maybe thats why he wants to do this - who knows.
-------------------------------------------------

I'm a little confused.  Are you saying you found out that your doc wants you to double dose by looking at the boxes and noticing that your're to take 360mg/week --  or did your doctor have this discussion with your prior? Because if it's the former, that's a h*ll of a way to find out. As to "who knows", I would make it my first priority to learn why your doc wants to do this, if indeed he does.

Obviously these are important issues, and if not already, I'd have a face-to-face - or at least a phone conversation -- with the doctor and make sure you know (and agree with) exactly what the treatment plan is -- doses, testing frequency, etc -- before you start to treat.

As you know from last time -- as we all know -- the best surprise in treatment is no surprise when it comes to getting from your medical team what you expect. And the best way to have no surprises is to make sure everyone's on the same page before you start.

And given what seems to be developing into a complex tx regiment, it might be prudent, after agreement between you and the doc, to write all of it down -- drugs, doses, test frequency, helper drug criteria, etc --  and then email it to him to once again confirm that you're on the same page.

Personally, if what I think you're saying is that you plan on double-dosing for 3 months -- I think it's overkill for someone like yourself with little or no liver damage in terms of risk versus rewards but I'm sure you knew I'd say that anyway.

-- Jim

[jmjm530]

NY,

Our posts crossed. I agree 100% with your advice.

[sfbaygirl]

As a relapser too, i sure would double dose for a while. Mistake or not, most likely not! Who prescribes 360mg a week?  Unless they mean it. We are in a different world, our chances of SVR are much lower. It it is too hard, do a half extra dose a week. With the Alinia and the DD, you are in uncharted waters, but I sure would do it! You sure don't want to do this again!

Linda

[sfbaygirl]

As a relapser too, i sure would double dose for a while. Mistake or not, most likely not! Who prescribes 360mg a week?  Unless they mean it. We are in a different world, our chances of SVR are much lower. It it is too hard, do a half extra dose a week. With the Alinia and the DD, you are in uncharted waters, but I sure would do it! You sure don't want to do this again!

Linda

[sfbaygirl]

As a relapser too, i sure would double dose for a while. Mistake or not, most likely not! Who prescribes 360mg a week?  Unless they mean it. We are in a different world, our chances of SVR are much lower. It it is too hard, do a half extra dose a week. With the Alinia and the DD, you are in uncharted waters, but I sure would do it! You sure don't want to do this again!

Linda

[Myown]

JIm agree 100% with what? GI issues, meaning parasites? Thats a 6 day Alinia tx, re- scoped and tested negative. So thats a non issue at this point. Parasites aren't like having IBS or something. Once they are txed - thats it. I am on Alinia still just so there wasn't any gap in between the para tx to the hepc tx.

But anyhow, never discussed dd, but maybe he thought of it as he was writting the script, who knows. Or it could have been a mistake by the girl who called it in. I have a feeling this is what he wants to do and Yes SFbaygirl, I agree with you, I want to do it, I would rather do this and give it my all than to do this stuff again. My husband is concerned if this is what the doctor wants, but if this is what the doctor says to do, I will do it. I'm up for it.

But anyhow Jim,I will talk to the doctor prior to doing this, if this is what he wants me to do and its not an error. This all came about yesterday - before that I hadn't noticed it said that on the boxes, so I just haven't had the time to call yet. I was in the city most of the day,,ENT (as mentioned) and then hung out- ate etc,,,so just didn't feel like doing all this phone calling and not in the mood after being at ENT anyhow.

As far as sitting down and writting the plan,,,he doesn't give me a hard time on anything when I ask. (Alinia, taper down etc) So I see no problem in being on the same page or not. As far as I knew, we were on the same page, until this 3 month thing, but I will have to check with him tomorrow or maybe he emailed me back, I didn't check my mail.

So I'll try to find out more tomorrow. I'll ask Doubledose if I can have his nickname and I'll ask Labrat if I can have his nickname for my middle name:)
seeya later,
MO

[sfbaygirl]

Good for you! So you are going to continue the Alinia, right?  Jim, if you had relapsed are you going to tell me you wouldn't have DD'ed too? I find that hard to believe, at least some half doses on top of the regular doses. I know you did some extra Riba, right?  Perhpaps a bit of extra Riba would be good...we don't want to kill the patient though!  Did you get anemia last time MO?  If not, I would ask for extra Riba!  Okay, MO you are ready for a name change anyway...you don't know what I am gonna call you! lol

Linda

[jmjm530]

MO,

I agreed 100% with NYGirl's post where she suggested a `consult with Dr. J., for reasons both NYGirl and myself gave. As to the rest, it just seemed odd that on one hand you're very involved in your tx plan with Alinia, etc -- but on the other, you don't seem to know how much Peg the doctor is putting you on -- sort of like the forest for the trees thing.

SF,

I did double-dose the first time. But only for three weeks, and only because I was told I was between stage 3 and 4. My understanding is the same as Mike Simon's -- see above -- that double-dosing makes the most sense for prior non (or slow) responders. MO was a rapid responder. Also, the usual double-dose protocol is to double-dose either until UND or for the first 12 weeks. I'm unaware of a 36-week double dose protocol and felt it adds more risk than reward to someone like MO who does not have significant liver damage, because the tx drugs are not without risk.

Because of all this, I'm suggesting what NYGirl is suggesting -- and that is that MO run all this by another doc, specifically Dr. J, who happens to be one of the best in the world and right in MO's own neighborhood. Personally, I'd also run the protocol by Dr. A. in Boston, but I don't expect everyone to have triple consults.

Hope this clarifies my remarks and I hope this finds you well.

-- Jim
-- Jim

[Myown]

I agreed 100% with NYGirl's post where she suggested a `consult with Dr. J., for reasons both NYGirl and myself gave.
-----------------------------------------------
Nah, as far as Dr. J,,,don't feel the need to do that. I am sick of running to doctors. I said to my husband, I should only know as many famous record producers as I do famous doctors.

"As to the rest, it just seemed odd that on one hand you're very involved in your tx plan with Alinia, etc -- but on the other, you don't seem to know how much Peg the doctor is putting you on -- sort of like the forest for the trees thing."

I did know the amount of peg as far as I am concerned cause he told me the only thing he would change was length of treatment.

I don't think I made myself clear though. When I said, do you remember the 6 months of interferon they sent me......yes it was 6 months worth at single dose, but not if its DD. It is 12 weeks worth. So you heard of 12 weeks being done for some?

If he did this and its not a mistake and after having a day to think about it, I am glad he did it cause I kept saying to him 'don't keep agreeing with me when I suggest something IF you think its a bad idea,,,,,you're supposed to be the genius, not me."

So anyhoo, in a way its good that he took it upon himself because he knows how I am and it shows it doesn't frazzle him. By that I mean "my obsessive behavior". Most doctors would have run it by me knowing how I am - neurotic. But this doctor takes me in stride just like my husband does and that's good and thats why I get along with this doctor so well. My husband thinks this doctor is the perfect match for me as far as being able to deal and he keeps his cool and has a great sense of humor. We are opposites as far as he doesn't cross all his T's nor dots all his i's,,but then again he has to deal with me double crossing T's and putting 2 dots on every "i."

So I'll see whats what. But Jim, I am trying to get out of my knee jerk approach to life. Its very unhealthy and I am starting to realize that. I was mad at first about not knowing about the dd, but now I am fine and yes I should have been told if this is really what he wants and is not an error,,,,but his good points far out weigh his bad and this is how I have to look at him, IF I expect people in life to do the same for me...cause we do reap what we sow..And I certainly need some slack cut now and then,,,and then,,,and then,,,,and then...............

[Myown]

I will ask him about the extra riba maybe for the beginning. I hope he says no. lol
I just took a sip of what I thought was juice from my husband's glass. It wasn't juice. it was Gatoraide - yuk!  

[jmjm530]

Yes, I have heard of twelve weeks double-dosing, but not in terms of previous rapid responders. But then again, I haven't had the opportunity to quiz your doctor on the "whys" of his treatment plan as perhaps you will assuming the spirit moves you.

Part of my response was because is due to articles I've read, part to a philosophical difference --  but part also was because I didn't want to see you going down the road of "surprise, suprise" as you did from time to time with your last doc and NP.

Again, the best way not to be surprised is not to assume, but to ask all the right questions before you start treating --  or at least before an event like a viral load test. If for example you expect  a particular test like a sensitive PCR instead of a CBC that might be on the requistion forum. Same with helper drugs, stop rules, extension rules, etc., etc. And if you expect to see the doctor instead of the NP, again, don't assume, ask, ask, ask, in advance.

Anyway, I've offered more than was asked, and it's your treatment not mine. I do wish you the best this time around.

-- Jim

[Myown]

Anyway, I've offered more than was asked, and it's your treatment not mine. I do wish you the best this time around.
------------------------------------------------------------------------------------------------------
No I like to hear it all and it doesn't need to stay just on the topic.

I appreciate all that you offer - you should know that by now.

Jim, I didn't know you dd yourself. Thats the first time I ever remember reading that. I know you did alot of extra riba, but had no idea you had dd.

You also said to SF "I did dd the first time."  I didn't understand that. You went thru tx more than once?

And I will only be seeing the doctor. That has been established. They even called me one day that he wasn't going to be there and said I know you only want to see him and re-scheduled me.

So I will see whats what.

Thanks again. Good night.
MO

[jmjm530]

No, I only treated once -- the wording of my post may have been confusing.

As to my own tx, it' been detailed here many times here the past -- but briefly,  I double-dosed between weeks 2 and 4, then went back to a single dose when I ended up in the ER from too much riba. (I also had over a four-log drop by then). The reason I started at week 2 was because that's when I switched docs.

Keep in mind that  I was under the impression that  I was between stage 3 and 4 and figured my odds of SVR were around 40% with SOC. Odds which didn't sit well with me.  The doc estimated that those odds could be increased maybe 10% with double dosing based on anecdotals from his practice.


-- Jim

[sfbaygirl]

Okay Jim....I understand you thought you were stage 3-4 by a failed Bx. You DD'ed for a while. Yes, MO didn't say she was doing it for 6 mos...just asking.  I know you. I know you would DD for longer if you were a relapser, to make sure. Yes, MO was an RVR, but that doesn't mean she will be this time. She is a relapser...a total different catagory! She has much less chance of SVR and needs to be more aggressive in tx.  Think about what you would do? You DD'ed during your first tx, RVR'ed at 4 weeks, right?  So why would you be opposed to her doing this now?  I don't get it.  As I suggested, she should do it until she gets to UND. Not saying this is a medical policy, but HR said for relapsers he believes in at least a half dose more during tx, of interferon. Why not? Hopefully, it won't be so bad. If it is stop. Kalio did so and SVR'ed as a relapser. She didn't have the Alinia too, but did use Oxymatrine....It is hard to hear you say that you wouldn't do the same. You and I are on the same page...I don't believe in tx'ing with low stages etc. But if someone is going to do so as a relapser, she has to be agressive. You know the stats for relapsers, why would you be so passive now?  Yes, we don't want to kill the patient, but if they are going to do it anyway, I have to think what I would do? Know what I mean?

Linda

[jmjm530]

SF: I know you would DD for longer if you were a relapser, to make sure.
---------------------------

My tx decisions were based on my stats and my advice to MO's is based on her stats. No, if I had MO's stats, I would not proceed as she outlined, without at least checking with one or two other doctors, as mentioned. We'll have to agree to disagree on this one.

-- Jim

[sfbaygirl]

She is going to re-tx, regardless of our suggestions. Given her stats, neither of us would re-tx at this time...okay?  But she is going on with it, so we are in a new ballgame here. we need to give her the room to do so and think about what we would do in her place as re-tx'ers.  Don't you think?  You went out of the box and DD'ed way before your time. Off the charts,no?  If I were to re-treat, I certainly would be aggressive, as I believe you would be too. You are way past this point, but think about it....wouldn't you think more aggressively than you did the first time? You certainly did the first time.  

[CockSparrow]

I like your Doc. Next time you see him, wanna ask when he is coming to Australia.
I wouldnt mind the same script you got.

So hope this works for you.
CS

[geterdone]

The only thing I can add is just walk into it slowly, meaning start off the first 2/4 weeks as to your last dosing regimen then from there step up gradually. If you start right off at the bat with the extra high dose your body will not handle it. Think about it from the first time and the sx’s with that dosing regimen and if you hit your system all at once with a higher dosage especially the Riba your plan will most likely fail because of the sx’s. I just went through this at week 45 and still had residual meds in my system and it was scary to say the least and could only handle it for 2 weeks because things started to go wrong. Anyway Good Luck in what you decide.

jasper

[nygirl7]

Just as a word of warning once the interferon destroys your thyroid - although the doctors say it can turn around again...I've not run into ANYONE who has had theirs all of a sudden start working. And I'm still stuck with loads of autoimmune problems that adeveloped around the same time - at week 30.

You were RVR that means that whatever happened to your treatment it was NOT interferon which was a problem. Taking double the dose won't do anything except UP the chance of developing serious long term problems that can't be fixed.

Seriously go to a Dr. J or A or XYZ but go to one of the biggies before you do this treatment because it is not sensible from a medical standpoint. You could end up much worse than you are right now.  Serously.

[CockSparrow]

I disagree. Not everyone develops thyroid issues even when Double Dosing.
In the High Dose studies I've read AI issues werent significantly higher.
Wouldnt a prudent approach be to monitor your thyroid among other things and then cut back if it looks like its taking a hit.
MO was a late RVR therefore taking 360 should mean RVR sooner and this hopefully would mean that the chance of another relapse would be significantly reduced.

While I think your warnings on AI are wise and certainly need to be taken into account by anyone undergoing Tx, It wouldnt change my mind in wanting to High Dose next time round. Those of us who have been thru Tx believe we know what we can tolerate (Possibly mistakenly) and Double Dosing does work.

The one thing I would do in MOs shoes is that i dont see the point of High Dosing after you reach UND. So I would cut back after this was achieved.

But then i am the kind of person that would take Infergen twice a day.
Just as well I cant get it ay.

All the Best
CS

[mikesimon]

She was undetectable at week 4 and I cannot recall whether she tested before week 4. If she didn't test before week 4 she may have been undetectable earlier. Aside from a study or two suggesting that 2 day VL might be somewhat predictive I think week 4 is the earliest point at which substantial data exists to make any reliable prediction about the likelihood of SVR. That's my understanding but I welcome any information you have to the contrary. Mike

[nygirl7]

Given the fact that she went UND so fast the first time around it's just not the interferon that f'd up on her at all - so it's just not worth the chance.  Once your thyroid starts to go (unlike what the doctors say) it's just NOT common for it to start working again, in fact I can't remember anybody at all who's did.

Considering most likely it was a lack of riba or some other variable that caused her to fail treatment - I would pursue a longer course of regular interferon and a higher dose of riba.

Believe me, I want my thyroid back.

By the way I would have done daily Infergen if I hadn't hit SVR after 72 weeks.

[sfbaygirl]

says, "By the way I would have done daily Infergen if I hadn't hit SVR after 72 weeks."  This is what I am talking about. We all want that SVR. Some of us don't get it and would do anything to get there. Yeah, I wouldn't want to lose my thyroid, but I guess we take our chances on tx. I am on bloodthinners for life and have fibromyalgia for life. I didn't even SVR. Does anyone think I would not now go an aggressive distance to get there, given what I have now given up in my life? I now have to deal with these two awful things... I would give up more if I could SVR. I sort of feel Iike I gave up a lot of my health for nothing. I was on tx and didn't SVR. So now I have to tx again? Nope, I am not willing at this time to do this again. I will try the anti fibrotics. Perhaps in the future, I will have to tx again....I sure hope not. I advocate for those that are on tx and those that need to, especially those that are stage 3/4 or cirrhosis/ESLD.  All scary things for those of us that haven't SVR'ed this virus. We have to wing it, in some ways. We put ourselves into the liver dr's that know what they are doing with non-responders or slow responders and relapsers.  We are a whole different ball of wax compared to those that respond and are SVR.  

MO was RVR, but she is a relapser. She needs more aggressive tx in the future. Look at the stats for us relapsers.  Tell me you wouldn't do more?  I know you went all out on your first tx.  What would you do on your second?  

[CockSparrow]

MO should verify this but from memory I think she was detectable at week 3 and UND at week 4.
I thought the day 1 or 2 VL tests being predictive of SVR were with NPIA.
Kinda goes like this.
After the first shot of Standard IFN your VL drops anywhere from 0.5 of a log to 2 logs. The rate of decline is dose dependant. This phase one decline stops at 72 hours and the phase 2 decline begins. The phase 2 decline is not dose dependant.

Now I agree that the studies state that there is no differnce in SVR rates between being UND at 2 weeks and UND at 4 weeks. With one exception. This is the Get-C G3 HVL study. This stated that week 2 UND was predictive of SVR. Zazza has posted links to it.
It does have one problem though. Its limit of detection was 600IU.

The PI studies drop your VL fast and you get to UND early, else viral rebound.
Makes sense to me that the earlier you achieve UND regardlesss of geno the greater your SVR odds.

So I ask this when would you rather be UND
Week2, Week 4, Week 12 or Week 24.

All the Best
CS

[CockSparrow]

I thought MO was on WBR last time round, If so upping further might not do much apart from making MO anemic. But I do understand where you are coming from. For me its not my thyroid that worries me so much as Aplastic Anemia. It might be rare for IFN to cause it but it does happen, not good.
That’s one of the reasons why I don’t think High Dosing should continue much after you are UND. We do have to balance our desire for SVR with trying not upset our immune system too much in the process.

Interesting difference of opinon though
CS

[mikesimon]

So I ask this when would you rather be UND
Week2, Week 4, Week 12 or Week 24.

I'll take UND 6 months post treatment.

Mike

[susan400]

If I could, just weigh in here on this discussion....    I feel that there is no 'set in stone',  and/or 'cookie cutter' approach to treating this disease.  Everybody needs to have individualized treatment, catered to their own needs, issues, etc.   While one person may be a chronic non-responder with damage already present in their liver.....  and another might be a naive for TX patient and another might have cirrhosis, and on and on and on.   Some people may have thyroid issues, others may not.  Some people may have anemia issues, others may not.  Some people may have Neutropenia, others may not.   I've treated these 9 times and my thyroid has not failed.  I'm not on any thyroid replacement.  I've not been on antidepressants either.  However, my white blood cells have been an issue for me with about every treatment.  Even with that, I still treated.  Just make sure that you contact your doctor and completely understand his recommendations.  Make sure that you stay on top of your labwork and keep your appts.  When you're going into uncharted terrritory, it's extra important to stay on top of things and not let serious issues develop.  I agree, that you don't want to kill the patient, but you do want to get your SVR.  God knows, I understand wanting to get SVR!  Otherwise, I wouldn't still be keeping my ears open for something that would be available for me, that would actually work!

Blessings to you,

Susan

[CockSparrow]

Touché

[Trish77]

Here is a study I've been meaning to post to you that I won't even comment on, I'll just leave it to you to determine if it has any value to you.  It's a study of the impact of double-dosing of INF on African American non-responders, who, as we all know, are in the harder to treat category.  

http://www.natap.org/2005/ddw/ddw_6.htm

Yes, you were RVR at 4 weeks.  That should have put you in the 80%ile or higher category for SVR.  But you relapsed.  That makes you an exception.  If it was me in your situation, I would double-dose too if I could take it....and I would start with a higher dose of riba.  Others have brought their riba down to a reasonable level but not to a below recommended dosage level.   The drug trial I'm in gives the trial drug for 26 weeks and then regular SOC for the remaining 26 weeks.  Perhaps your extra dosages are like giving yourself a trial drug.

All of this comes with risk, even regular SOC does.  If you know you are going to choose an alternate uncharted route of treatment, then I'd hope you plan to monitor yourself all the more stringently and have a pre-plan in place for what you will do if you hit danger territory.  

If it was me...and I had RVR'd and then non-responded against the high odds of SVR for RVR's...I'd be looking at what I think was the culprit last time and do it differently this time myself.  

I wish you good luck with your decision.  

Trish

[mikesimon]

Non response is not the same as relapse. If I am understanding the African American article correctly, the study cohort was comprised of non responders to interferon and ribavirin - I don't believe that they were non responsive to pegylated interferon which, as we know, is a more effective treatment drug than regular interferon. Regardless, they were not relapsers - they were non responders.
I am not adverse to any treatment approach that has some basis to believe will be effective. I just do not see a reason to believe that double dosing Peg will improve her outcome. She did become undetectable at 4 weeks so it seems to me as though the Peg did the job. Had she had a slower response I would see some basis to believe that an increase of Peg might be beneficial but, that is not the case here. We can speculate that becoming undetectable earlier (say at week 2 or 3) might result in  a better outcome - it does seem intuitive - but we really don't have any substantial data on which to base that conclusion. And I am not certain the double dosing has been shown to accelerate HCV clearance in previous RVR relapsers - I haven't seen anything that suggests that. The vast amount of data available suggests that 4 weeks is the critical time at which to determine the likelihood of a positive outcome and, since she satisfied that criteria (UND at week 4) the Peg/ribavirin worked as it should work. In type 1s it has been shown that extending treatment and maximizing ribavirin exposure gives relapsers the best chance of achieving SVR. Although 2s seem in some ways to be distinct from 1s it appears to me as though, in this scenario, extending treatment seems like the most reasonable approach. Having said that, aside from the side effects that might accompany double dosing  Peg, I can see no harm, insofar as treatment response is concerned, that could result from double dosing. But side effects can be a serious issue. I just don't see the upside in that approach but, if it is tolerable without any serious side effects, I don't think it would hurt her chances of SVR.
You said that: "If it was me...and I had RVR'd and then non-responded against the high odds of SVR for RV R's...I'd be looking at what I think was the culprit last time and do it differently this time myself."
I agree but I think that the amount of time spent undetectable is more likely the culprit with relapse and RVR and that is what I would do differently - extend treatment. I would do 48 weeks and standard dose of Peg-interferon and the optimal dose of ribavirin.
And by characterizing her outcome as "non-responded against the high odds of SVR for RVR's" is rather loose language in the HCV vernacular. Using "non responder" to describe a "relapser" sort of begs the question. If she truly was a non responder then double dosing Peg would be a reasonable approach - but she wasn't - she relapsed.

Mike

[jmjm530]

Pretty much agree with Mike's wrap up. So, putting aside the added risks of more interferon, if MO does decide to proceed, what might be useful would be to test vl weekly as before, to see if the viral decline with DD gives her an earlier RVR. Frankly, and this is anecdotal like so much of this stuff, I think she'd be better off pre-dosing riba like FLGuy, not only to possibly achieve an earlier RVR (FLGuy was UND at week 2) but because riba is often talked about in terms of it's role in preventing relapse. The riba also might be maximized to a certain extend as well, but again more drugs, more risk.

What I see the downside to her doctor's approach is if he thinks that double-dosing will replace extending to 48 weeks, which I'm not clear if he thinks it will. If so, I'd definitely speak to someone else, but I've said that before and MO doesn't want to.

Trish, your point about changing something when tx doesn't work the first time is spot on and covered quite well at the Clinical Care Options web site. You might start with "Doc Eye for the Hep Guy" with Drs Dieterich and Jensen. I'ts an excellent site to see how many top clinicians are extrapolating current trial data in to actual treatment programs. http://www.clinicaloptions.com/  But as Mike suggests, you want to change the right thing to give it your best shot. No doubt a shot-gun approach has the greatest probability of SVR but it also has the greatest probability of doing harm, perhaps long-term harm to the patient.

I've often talked before about how many of us go into "warrior mode" around the time we start treating and during treatment. And while warriror mode can often make the difference, it can also allow some of us to over-treat. If SVR is the only goal then it doesn't matter, but a careful reading of the archives here shows that these drugs are not without risks.

-- Jim

[jmjm530]

Let me just re-phrase part of that last paragraph to say that "If SVR is the only goal then it *often* doesn't matter". I added the "often" because in addition to the risks of xtra drugs to our system, there is also the risk that higher doses might put some of us in a position where we actually have to dose reduce or even go off the drugs and not complete the course.

[sfbaygirl]

Yes, I agree with Mike's take, as well. To a point!  Let's say that RVR is 4 weeks...that is the gold standard these days, right?  So, if perhaps we do Flguy's riba pre tx for a week, DD until we get to UND, then go back, perhaps slowly (half doses) for a few weeks to not shock our systems. That sounds prudent to me. I am not talking about non-responders. That could be a whole new ball of wax, or not. Relapsers, or slow responders (like me) possibly could become RVR if doing DD for a few weeks, as described above. Non-responders could do the same and if there is still NO response....stop!  I don't want to kill the patient (me) just give a better chance of response. Now, I am not sure about how slow responders once UND, hopefully at week 4 will respond once that DD is no longer given. Perhaps a 1 1/2 dose for longer. I know Kalio did this. We are in uncharted waters, as we know, but what is wrong with the patients who understand this stuff a bit to mix it up a bit?  As a slow responder and someone who had lots of problems, if I were to re tx, I would certainly do at least a bit of DD'ing at first, then slow it down. Do those weekly PCR's at first and not let the Dr. or ins. co tell me only every 12 week PCR's. This is too important for others to make these sometimes stupid decsions. I was unaware last time, I listened to some idiot, instead of learning enough to begin with. I won't make that mistake again. I also won't make the mistake of not taking some risks on tx to get to SVR, that many Dr's won't do. I certainly won't take enough chances to kill me, I will have CBC's every week or less, and PCR's every week. I hope when and if I do re tx, I have a Dr that will go somewhat along the lines of what I believe is the best course of tx, as MO does.

Linda

[Trish77]

Mike:  And by characterizing her outcome as "non-responded against the high odds of SVR for RVR's" is rather loose language in the HCV vernacular. Using "non responder" to describe a "relapser" sort of begs the question. If she truly was a non responder then double dosing Peg would be a reasonable approach - but she wasn't - she relapsed.
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On that then, I am speaking entirely out of turn and the article is improper. I'm at least relieved that I refrained from commentary on the misapplied article.  I thought MO was a non-responder in my head...and I confess, sometimes I get mixed up between the two terms - non-responder and relapser - although, a little bit of thought would make it clear what each term refers to.  Obviously I need to go back to the classroom.  

Jim:  I've often talked before about how many of us go into "warrior mode" around the time we start treating and during treatment. And while warriror mode can often make the difference, it can also allow some of us to over-treat. If SVR is the only goal then it doesn't matter, but a careful reading of the archives here shows that these drugs are not without risks.
-------------------------------------------------------------------------------------------------------------------
Well....I'm not suggesting ANYONE, including MO take a "scattergun" approach and hit it with whatever is in the arsenal.  I did suggest that she plot out what dosage she would start out at, what the plan would be if she had to reduce that dosage and to make sure that careful monitoring takes place as she goes along.  The suggestion to have a plan in place in the event she needs to reduce dosage would, I hope, be a carefully thought out approach that has viability...rather than an on-the-fly approach because one just loaded it on in what you call "warrior" mode.  I know I've talked of slathering on blue warpaint and all that in the past ... but I DID leave that out of my suggestions here. :)    Anyway...your points are well taken and I happen to agree.  No dispute with what you've said at all.  I do think none of this is anything to be taken lightly.  If I inferred otherwise, then I worded my comments poorly.

[CockSparrow]

“Trish77 - I'm not suggesting ANYONE, including MO take a "scattergun" approach and hit it with whatever is in the arsenal”

I am. Shock and Awe is the way to go. Scare the little buggers to death.
Double Dosing for 4 weeks isn’t that high a dose anyway.

The following comes from the Pegasys Insert;
Overdoses with PEGASYS involving at least two injections on consecutive days (instead of weekly) up to daily injections for one week (i.e. 1260 μg/week have been reported
None of these patients experienced unusual, serious or treatment-limiting events. Weekly doses of up to 540 and 630 μg have been administered in renal cell carcinoma and myelogenous leukaemia clinical trials, respectively.

Dose-limiting toxicities were fatigue, elevated liver enzymes, neutropenia and thrombocytopenia consistent with interferon therapy.

Now if you didn’t have the above dose limiting toxicities, why would you have them the second time round. We arent talking about daily shots here. Only 360ug and then only for a relatively short period.
Anyone up for daily Pegasys, god that would have to hurt.

To my way of thinking it’s the length of time on the drugs that causes most of the serious AEs.

From the Pegasys Insert;
In comparison to 48 weeks of treatment with PEGASYS and COPEGUS 1000/1200 mg, reducing treatment exposure to 24 weeks and daily dose of COPEGUS to 800 mg resulted in a reduction in the serious adverse reactions (11% vs. 3%), premature withdrawals for safety reasons (13% vs. 5%) and the need for COPEGUS dose modification (39% vs. 19%).

For me doing 48 weeks or longer is of more concern that Double Dosing for short periods.
CS

[Trish77]

Cocksparrow:  “Trish77 - I'm not suggesting ANYONE, including MO take a "scattergun" approach and hit it with whatever is in the arsenal”

I am. Shock and Awe is the way to go. Scare the little buggers to death.
Double Dosing for 4 weeks isn’t that high a dose anyway.
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Then why not triple or quadruple dose then?  Why not load up on the riba and take it 4x a day instead of 2x?  Double or triple dose the riba too...and if you can take it as you go, just keep increasing the amounts.  Shock and awe, right?   I'm being ridiculous but the point I was making in the first place is that while I agree with "hit it hard out of the gate" there has to be some intelligence to the approach and some thought put into it.  You want sustainability, SVR, and you also don't want to kill the patient as Jim keeps saying.  So I prefer a calculated risk approach.  Believe me, I'd rather take some risks, push the limits and kill the buggers.  You talking about double dosing for 4 weeks is actually conservative to me.  

I'm thinking that both Jim and Mike don't see the need for double-dosing in this particular instance for MO.  I don't think they'd necessarily be against it across the board.  I'm sure they'll correct me if I'm wrong on that interpretation.  :)

[Trish77]

Now that I've got my terms straightened out...mostly...

If I recall right, the odds of SVR for a person reaching RVR increase not to 100% but pd close to somewhere around 80 - 90%.  So there is still that leftover + or minus 10% that will not SVR after an RVR at 4 weeks.  And MO falls into that group.  

Makes me wonder, MO, what sensitivity of test was used to monitor you all along and how often?  I'm just curious about that.

Aside from that......if a person relapses, then all the critters didn't go away.  It's not a re-infection, correct?

And if all the critters didn't go away ... when would you most like to kill off as many as are detectible?  I think I would prefer to dose harder and dose earlier to once again hit RVR and extend that for awhile...beyond UND.   And if one is not achieving RVR at double dosing...which would take only 4 weeks to find out.. then I would potentially cut back on the extra dosages at SOME point and move to extending treatment with regular SOC.   Is there really any harm in choosing a period of double dosing in the beginning as long as you are monitoring effectively and stringently all the way through?  I'm asking rather than suggesting.

Trish



  

[jmjm530]

You're an exceptionally fast learner, but still relatively new to this, and "terms" more than matter :)

Not sure where what study you picked up the 80% figure from, but no doubt it was a geno 1 study. MO is a genotype 2, meaning she has aournd an 80% chance of SVR from the start, not just if she achieves RVR, which a majority of geno 2's do.

As to the rest, MO used a very sensitive test, down to 5 IU/ml if I remember correctly.

As to what causes relapse, anyone here who can say with certainty is a lot smarter than me or any doctor that I've read.  

But yes, as you suggest, all the "critters" don't go away when we're UND or we could stop treating as soon as we become UND. As to what's really going on, theories abound, including the sensitivity of the tests themselves and the dance of the immune system.

Remember, interferon -- unlike the PI's -- does not directly kill the virus. What it does it stimulate the immune system to kill the virus. For this reason, some liken it to a sludgehammer trying to hit a tiny nail, because no doubt the sludghammer will hit more than the nail, but I digress :)

Because of this indirect action, the concept of double-dosing in previous RVRs is questionable because the immune system has already demontrated it reacts well to the interferon.  What is more reasonable is that the interferon immune system training may not have been long enough. Therefore the concept of treating non-responders hard early (double-dosing as one example)  to foster RVR, but   treating relapsers (those who responded like MO) longer because they so to speak needed more time in summer school to graduate.

Did you go over to the Clincal Care Options site and listen to some of the teaching modules. Not that re-inventing the wheel with HCV treatment isn't reasonable given so much muddle in this field -- but always good to see how the wheel was invented in the first place by today's top wheel builders.

You ask "Is there really any harm in choosing a period of double dosing in the beginning as long as you are monitoring effectively and stringently all the way through?"

First, and this should not be taken lightly, these drugs are toxic and have consequences, so simply adding a drug (or increasing dosage) should never be taken lightly.

But that aside -- and it's a big aside --  my problem from the get go hasn't been so much that MO wants to double-dose, but that her medical team seems to be hanging their hat on this approach. In other words, a *better* approach might be to extend, whether one double-doses or not.

In a way I'm saying that the continued focus of this thread on double-dosing for a previous geno 2 rapid responder may be missing the point entirely, which is what is the best way for MO to approach her second treatment.

As stated, I'm skeptical that this is the right approach, and if in MO shoes I would "test" this approach with one or more hepatologists that I've mentioned and that MO has access to. They may agree with her current team, they may not, but no doubt they will add information to the decision-making process. Of course this suggestion reflects as much who I am as what I'm suggesting, because this is how I approached my treatment -- testing one approach against another using study data and what the collective wisdom of several top hepatologists, who did not always agree.

-- Jim

[sfbaygirl]

Trish, I believe MO had a very sensitive test throughout last tx. As we also know about 2's and 3's is that sometimes that 24 weeks just isn't enough. I agree that hit those critters at first, but will that be enough?  I know both Flguy and Kalio did things differently. Flguy did the Riba a week before tx. Kalio did 1 1/2 doses of INF about midway through tx along with oxymatrine, another thing to perhaps add to SOC.  I believe Flguy DD'ed the first few weeks. Both are SVR now.  Of course we don't want to kill the patient!  As CS pointed out, INF can be taken in much higher doses and is for cancers. So why not us? Perhaps even those non responders weren't getting enough INF. YOu know that everyone's body has different tolerences. I am sure one could tell pretty quickly how much is too much. Kalio was more tired doing the extra INF, but she was okay.  

I agree with Cocksparrow about shock and awe, but not to the point where one has to stop tx because one took too much. By the time we finish tx the first time, we do sort of have an idea how much we can handle. After that first shot, I didn't feel many sx from them besides the fatigue. So I would do DD in a second tx, at least for the 4 weeks and possibly 1 1/2 for awhile, besides the tapering at the end.  Yes, I think a Dr. needs to be on board and keeping a close eye!

Linda

[sfbaygirl]

I think we cross posts!

[geterdone]

OMG!!!! You scared the patient off… she hasn’t posted in days, lol

jasper

[CockSparrow]

OMG!!!! You scared the patient off - Made me laugh.
CS

[sfbaygirl]

OMG! I hope we didn't kill the patient already! LOL  

[CockSparrow]

Trish
Then why not triple or quadruple dose then?  Why not load up on the riba and take it 4x a day instead of 2x?  Double or triple dose the riba too...and if you can take it as you go, just keep increasing the amounts.  Shock and awe, right?  

Yeh it is shock and awe, and to some extent its been done. Tx is a compromise, you have to be able to tolerate it, having a life during Tx comes into to.

High Dosing Riba is risky you will end up in Hospital needing a tranfusion, but in at least one study (Lyndal - spelling) taking up to 3600 mg it does work 90% G1 SVR rate. But god it was harsh. All patients needed EPO and several needed transfusions.

Jim and others are right these drugs are toxic but to my way of thinking its no accident that those who complain about the drugs toxic effects have mostly done extended Tx.

CS

[sfbaygirl]

I asked HR about DD'ing infergon, he said he didn't recommend it. He said they did a study doing just that and hardly anyone made it through!  It was so harsh.  I'm not so sure about the extension of these toxic drugs as being the thing people on tx complain the most. I am sure it isn't great, but it sure seems some of us really experience more sx than others. Also, it seems that those who don't end up with anemia or lower HGB, end up not clearing. Of course this is anecdotal, but I remember Fishdoc's Dr. had her up her Riba as she wasn't getting enough and didn't get UND, until she upped it over what was weight based.  Possibly some non responders aren't getting enough IFN?  

[geterdone]

Hey! if myown post a picture with crossed amo belts... I'm outta here, lol!

I did not extend that far but see my journal and hopefully myown will too.

jasper

[jmjm530]

CS: its no accident that those who complain about the drugs toxic effects have mostly done extended Tx.
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Assuming this is true, and I have a hunch it may be, it doesn't change at least what some of us have been saying. It's not solely a matter of toxicity (double-dosing for a shorter period of time verus single-dosing for extended) but of efficacy. From my experience, sure, I'd rather double dose for 4-6 weeks and treat for 24 as opposed to single-dosing for 48 weeks. BUT only if something told me that the double-dosing would give me a better shot of SVR. If not, then it's really academic.

-- Jim

[sfbaygirl]

Here is a possible tatto for MO!
skinu.com/site/search/style_skinu%7C20578/search.htm

[mikesimon]

I have nothing more to add other than to say that Jim and I are in total agreement on this issue. Mike

[Trish77]

I have nothing more to add myself...I simply don't know enough to make any useful contribution here.  I am very interested in the discussion however and I think I'd best simply sit back, read and learn.