double dose for 72 weeks

[koala68]

I am about to start a new treatment in December with twice the interferon (two shots of pegasys every week instead of one) and standard dosage for Ribavirin.
Has anyone experience/advice following the same TX?
I am genotype 1b. 40 years old with stage 2 fibrosis. I responded well to my first TX (52 weeks of standard pegasys/riba) two years ago but relapsed after 3 months. First time was not too hard overall. Did not miss a day at work, but I know this time will probably be tougher.

[FoieGras]

Thanks for sharing your story, it's given me more hope that I am on the right track. I am 50yo, Genotype 1, Stage 3, pretreatment viral load 800,000, treatment-naive, less than 1 log decrease at 4 weeks, and negative HCV RNA at 12 weeks, currently 30-odd weeks into a planned 48-52wk course of IFN 150mikes every 4days and RBV 800 twice daily.

What you are suggesting is the same that my doctor suggested: I investigated it and found that the half-life of the pegIntron is such that viral breakthroughs happen day 4 to day 5 after the injection. In fact you can show this using data available in the literature and some basic pharmacokinetics.

Double dosing - or rather, decreasing the dosage interval - the Pegetron product(peginterferon alfa2-b) actually makes sense pharmacologically.

Thanks for reminding us all that even at the end of this grueling Rx, some of us will relapse, even though EOT can be negative...

I firmly believe in being very aggressive with this virus on the first treatment, and I hope it's not just faith talking.

I have had some difficulties with anemia and depression, but there are medications for that. The interferon really affects my mood and it's tough to take the damn needle when you feel so lousy for a day or so after - but I am probably predisposed to that.

Best of luck to you.

[koala68]

To CockSparrow,
Thanks for the data. I could not find a lot of data about fatty liver condition. How can I improve mine? Loosing extra weight? Exercising more? Eating less proteins? I've read that starving yourself too quickly can create these symptoms in healthy people. That's one of the known side effect of getting the stomach bypass surgery. Otherwise, I'll try to get checked for possible insulin resistance/glucose abnormalities.

To PegM,
Were you taking the two shots at once or one shot every 3.5 days? There was a post on the forum showing that it can makes a significant difference. Good you could be put on maintenance therary. BTW I think we have the same Hepatologist :)

To Magnum,
Thanks! I'll keep you guys updated about my situation.

Can someone extend on the autoimmune disorders they got and how it is affecting their health?

[Magnum]

I'm sure that not only I, who may start the Pegasys double-dosing in January, but others as well, would appreciate your timely reports once you start. Best of luck in clearing...

Magnum

[PegM]

From a subjective point of view, my double dose treatment wasn't twice as bad as the single IFN/ribes, but maybe 25% worse at most.  I'm in the same physician group as you and am convinced that double dose is worth trying.  The problem with the VX-950 clinical trials is that the open label trial for relapsers won't start for a few months, and it is the only one where you can be certain you're getting the protease inhibitor and not just a repeat of your original IFN and ribavirin, because it IS open label.  I had HCV RNA show up in the middle of my double dose, so am now on a maintenance mono IFN treatment to suppress it the virus until the open label trial starts.  I completely trust the knowledge base of Gish, Cooper, and some others in this group.  They're cutting edge hepatologists.
Take care.
Peggy

[Magnum]

I'm in Las Vegas, but Dr. Gish comes here twice a month...

Magnum

[CockSparrow]

"koala68 - I do have mild macrosteatosis/fatty liver condition."
If you are G1 and have Fatty Liver you will likely also be Insulin Resistant to some extant.
If you can lose or at least reduce the Fatty Liver and IR then that in itself would give you an excellent shot at svr.

You need to have both your Glucose and Insulin checked.
Ideally in both the fasting and non fasting states.
Once you have this you can then calculate HOMA-IR.

Its possible for F2s to progress to cirrhosis in under 10 years.
So retreating now makes sense to me.

As for retreating
According to Schering retreating G1s prior Peg non responders has a 12% svr chance.
Not worth it really.

However this doesn’t paint the full picture.
The svr rates for prior Peg NRs
F2 = 23%
LVL = 29% (LVL=600K)
Prior Relapser = 36%

OK but not brilliant. It gets better though.
37% of prior NRs had cEVR. Of these 57% SVRed.
Now the odds start to look a liitle better so long as you are UND at week 12.
Btw non evr had a 0% svr rate in this study which was Epic3,
pEVR only had a 6% svr rate. pEVR= 2log drop or better, but not UND.

Now for DoubleDosing.
Unless you find yourself in the same situation as DoubleDose and respond slowly even at high doses, I don’t see the point of high dosing much past becoming UND.
Just cant see the benefit.

However high dosing should improve your chance of being UND at week 12 and is therefore worth a shot.
Adding Alinia would also improve your svr chances. As does extending to 72 weeks.

In other words Jims 50-50 shot at svr could easily become 80% or better.

As you didn’t find last Tx difficult there is no reason to expect that it will be any different next time even with high doses.

All the Best
CS

[koala68]

I see my Hepatologist again in about 2 weeks. I'll think more about the different options brought up here and discuss this more in depth during my next visit. Knowing how sneaky my health insurance is, the insurance company will surely try to deny the extended treatment anyway, so ironically, that might be a "good" thing this time.
Thanks again for all your help,
Koala

[jmjm530]

1/29/2006 16.6
8/25/2006 started TX
10/10/2006 14.8
-----------------------------
Koala (prev) Has anyone experience/advice following the same TX?
---------------------------------------------------------------

First, I want to thank you for taking some of the comments -- mine and others -- in the spirit they were given. That spirit being that we all really care about you and are therefore giving our heartfelt advice and  opinions, which you specifically asked for in your first post. I hope at least one member takes note of your initial post as she apparently thinks you were not looking for advice and are being run off the forum with our comments which obviously you are not.
----------
As to the whole issue of insulin sensitivity, there are others here more knowledgeable. "Co-Writer" for one, and you also might want to pick the brains of the Gish team. If the NP isn't up to speed, move up a level or do your own research.
-------------
The hemoglobin/riba thing. It appears that your started hgb would be around 16.6 but the next value you posted (14.8) was five weeks later. Did they run any CBCs inbetween? In any event, you did have around a two-point drop in five weeks which suggests riba absorption, but again hgb values are a crude barometer as compared to HPLC serum riba testing which is not avail in this country. All said, and given that you hgb always stayed above 12 - pared with the fact that you seemed to feel OK during tx -- I think the concept of raising your riba merits a discussion with your doctors because you did relapse and riba is one component in the mix. Of course, I'd prefer to see you not treat at all -- or certainly not as proposed -- but you already know that :) Still one last shot -- right now you're proposing 72 weeks of DD Peg with probably less than a 50-50 shot at SVR, perhaps very much less. On the other hand, the newer PIs are showing over a 50-50 SVR rate in prior relapsers with only 24 weeks if I remember correctly (and please someone correct me here because I'm not up on the studies). And that's just for geno 1s. Possibly geno 2's would require even less time. If you could be patient and wait a few years while having your med team monitor your liver, you may be able to limit your interferon exposure significantly with a better chance at SVR.

All the best,

-- Jim

[koala68]

Jim,

So far my glucose level seem to have remained within acceptable range over the years so insuline resistance has not been specifically checked, but it is something I'd like to pay more attention to in the future as HepC carriers are apparently more prone to diabete. As you said, people don't need to be overweight to develop it. I was thinking to get myself one of these glucose meter to frequently monitor over time. Would that be enough or should I request the specific glucose fasting blood tests available?
Otherwise, I do have mild macrosteatosis/fatty liver condition.
My Hgb was measured at 16.6 before TX and evolved as follow over time:
1/29/2006 16.6
8/25/2006 started TX
10/10/2006 14.8
11/7/2006 13.2
12/26/2006 13.3
1/16/2007 13.3
1/23/2007 13.8
2/13/2007 13.5
3/10/2007 14
3/30/2007 14
5/4/2007 13.4
5/25/2007 12.8
6/27/2007 13.4
7/31/2007 12.7
8/24/2007 12.8 Finished TX
8/6/2008 16
Looking at these numbers, do you think my Riba intake was too low?

Something to note: As a result of a mistake made by my Insurance, I was out of the drugs for about 5 days in Jan 2007 but was able to catch up immediately after that. The TMA next week did not show a relapse then, but I am still wondering if this may have negatively affected the overall outcome my TX.

To Copyman,
My hepatologist did not push me one way or another but listed the different options available to me such as waiting or treating by trying to enter clinical trial, or retreating with Riba+Inf therapy.

To Geterdone,
I lost some weight in preparation for my treatment (as suggested by the Hepatologist) but my weight remained amazingly even during the entire treatment:
Around 176 pounds when I started, 174 when I finished. I did gain about 10 pounds since TX finished.

To Comeagain,
You are right. Nothing is certain until it's really there. Some drugs are even pulled out of the market (like Vioxx? a few year ago).  
For instance the same biopsy sample can be assessed differently depending on the person who is checking it.
My hepatologist requested to see the slide after initial report was written and reassessed it as stage II.
  
To Ladywhy, Doubledose
Thanks for the support. Doubledose could you please comment on the autoimmune problems you developped?

To FIGuy,
I may have underestimated the risks involved going the DD way,  because my first experience with treatment has only been positive to me despite the relapse.
For instance ALT/AST remain now in range which was not the case before TX.
I don't have any side effect from it but that could change if I DD. I forgot that rescue drugs are not going to protect against some of the severe side effects.
Also, the lack of extensive data about Infergen/DD is frustrating.

To Magnum,
No wonder!
FYI: I am in the Oakland center. What about you?

To Goofydad,
Thanks. see Hgb above

To MeeryBe,
Well good points. Giving the liver a break is not necessarily going to help if everything else gets broken.
I don't smoke or drink but exercise regularly and eat more healthy. I get a lot of fiber in my diet which is also something to take into account for a next TX.

All,
Hope I have not forgotten anybody! Again the feedback from everyone regardless if it is for and against is very appreciated. It helps me decide what to do next.

[merryBe]

seems like you are between a rock and a hard place. A lot of folks seem to have not cleared in 48 wks. who are type 1.  Perhaps one day SOC durations will change, hopefully the new PI's will lower times, but on the SOC now...I think more time has shown the greatest successes.

Here's my BIG BIG question: How is doubling your interferon going to give your liver a REST?  I'm sorry but all I read on DD'ing...none of it involves resting the organ.

I know in theory that the normal dosing in some, not all, but some patients SOC does slow the rate of fibrosis, even seeing stage reversals have been documented.
Remember though that a dose that helps and a dose that overwhelms can have very different effects.

Double dosing is a different story, it is not SOC for many reasons.... because the body's response to double can be deleterious to several organs. Not to mention that autoimmune issues become much more pronounced and likely to evolve. There's a long list of possibly much more adverse outcomes.

Then too, Riba absorption plays a big part as mentioned. Unfortunately they don't test for that directly, but if your blood continued to drop you probably were absobing enough, if it didn't then maybe you weren't. I didn't know when I started tx that eating fiber was interferring with my Riba absorption.

True, HCV is not linear, especially if you are coinfected with HIV, however, if not, and if you don't smoke or drink, then I'd say your chances with the new PI's and maybe adding Alinia as well (I would) would give you a much better shot at SRV in less time and with less potential damage.

If you look at this pragmatically...we are almost through 2008...2010 isn't that far away.
it could be that a PI regime begun in 2010 would have you ending tx at the same time as a double dose regime begun now would.....give or take a month.
Plus your odds of SVR double and your tx time is cut down to 1/3 the time.

so,

for my money, given my DD experience was similar to Jaspers (the week from hell)...
and given your age, still young, stage, and not knowing ALL the other factors, I'd say take care, take antifibrotics for now, ala HR style (see HHealth Pages, HR's advice) and waiting for the big guns to come on line.

But whatever you decide, I wish you well, and will say a prayer for you.

MB

[orleans]

not me, no way, think i'ld take the little critters

[GoofyDad]

I wouldn't rush to retreat at stage 2 either....

[GoofyDad]

THe possibility of a riba metabolism was touched upon by Jim above. Since you said you handled the 1st treatment so well, I'd be curious what your hgb declines were. If not significant, I'd include not enough riba on the short list of things that might need changed. You could double the INF unneccessarily, when really the riba was the problem.

    

[Magnum]

It's no wonder your doctor Gish has the same protocol of weekly blood work, he's my Hepatologist as well...

Magnum

[copyman]

very puzzling to say the least. you are with the Gish team and they have not recommended one of the PI's which have shown around 80% "CURE" rate in relapsers! especially those that responded very well which it seems you did. like you said you can change your mind if you want. get into a PI trial and kill the virus in ONE YEAR or less.  some like myself look at this as a no-brainer.  what a shame to do another 1.5 yrs of meds then god forbid you relapse again, or non-respond this time or worse case scenerio build up a resistance to the drugs! then you are screwed for ever! here is something else to think about,  if you are ulucky and the 72 weeks don't work then you do another year with the PI's, that will be over 4 years of your life wasted with harsh drugs in your body!  You have received some great advice from the folks here. This is a very personal decision only you can make. Best of luck whatever you decide.

[ladywhy]

I agree with you.

I was really commenting on the many negative posts following Koala's question. I would not be surprised at all if koala doesn't come back here for support or post about his/her tx. Koala did not ask anyone's advice about tx...only if anyone had done it.
I myself chose to stop posting publically about my tx 'cause it was not helpful to get negative feedback...at ALL.
Some may think they are experts...but I prefer to talk to my dr. face to face and go over my concerns with him/her. or get another opinion from a top Hep C expert, a doctor.
I advise everyone before tx....to do their own research. The only problem with DD is there are not too many if any studies out there. So happy to hear Double Dose has obtained SVR!

With this illness, it is hard to be optimistic, but better to be that, than depressed and hopeless.

FlGuy" Always enjoy reading your posts.

[FlGuy]

I really didn't mean to imply that Koala was optimistic himself. By that comment I meant that people, in general,  need to keep optimisim out of the decision equation. "Wanting" to get SVR does not kill a virus. Treatment decisions, in my opinion, need to be coldy calculated.

[DoubleDose]

I did a double dose course of  Peg Intron/ Riba for 72 weeks, after having relapsed two years earlier immediately after a 15 month course of increasingly frequent Intron and Infergen dosing, along with Ribavirin.  I relapsed within two months, and most likely because I had not stayed undetected for a long enough period of time  (5 months undetected toward end of tx), and that I had to cut the Ribavirin down to less than half the optimum dose during the last few months of tx due to anemia. (no Procrit available at that time)

My second tx consisted of larger than normal weekly doses of PegIntron, which worked out to about double the recommended dose for my weight, on a weight based dosing formula.  I was also able to keep the Ribavirin at mostly full dose throughout my tx by using procrit.  Since I became undetected at about week 19 on this tx (technically a late responder), my doctor decided that 72 weeks were absolutely necessary to have a good shot at SVR.  I fully agreed.  I DID GET the SVR and its been over 5 years since I finished tx.  

I do have some follow-on sx, and autoimmune problems, probably from all the months of high dose Inf. over two tx'es, but I would say that I am very happy that I did what I did.  I feel much better having NO VIRUS, and normal liver functions, etc.  I do not think that double dosing the interferon is as drastic as some might believe.  Its not exactly additive on a 1+1 scale.  Many cancer patients use much higher doses than the double dosing.
I sometimes think that for susceptable individuals, a low dose of inf. may be as problematic as a very high dose.  It all depends on how YOUR body responds.  I have read of some who did only ten or fifteen weeks of tx, and stopped due to drastic reactions, that lasted long term.  Others have done five and six rounds of tx, and are still going strong.  I have a friend that did three tx'es, his last was for two years, at high dose.  He got the SVR, and now feels pretty good overall.

You may wish to discuss using another interferon with your doctor.  Peg-Intron sometimes works better when Pegasys has failed (and vice-versa), and might get you and early undetected.  You might be able to get the result you seek with only a minimal increase in standard Peg-Intron dosing...and you can determine whether it is working properly by testing at weeks 4, 8, and 12 during early tx.  I think that full dose Ribavirin is also extremely important to avoiding post-tx relapse.  This has been demonstrated time and time again.  Using Procrit or other hemo-boosters can allow you to sail through the course of combined tx.

So, in all, yes you could wait for the green flag to use the newer coctail tx'es, but you will still be using interferion with it.  The question of when it all becomes fully approved for patient use is still unclear.  You may be able to get through an extended tx now, with minimal to moderate side effects, if you are lucky, and supervised well by your doctor.  I would never advise someone NOT to go for the SVR.  We know that extended tx, as well as customized dosing has indeed been shown to achieve much better results in a variety of recent studies.  Our on-forum list of extended tx SVR's is a testament to that.

Just work closely with your doctor to find the very best solution for you, and what you want...balanced with your personal risks of progression of HCV, and where you are currently in medical terms.  If you had minimal autoimmune and depressive problems from your first round, you might indeed be able to do the extended tx, at higher dosing without serious problems.  Your doctor will need to monitor the tx closely as you go.  Good luck and best wishes for a decision that ends up working best for you.  See what your doctor thinks about Peg-Intron vs. Pegasys.  

DoubleDose

[ladywhy]

Can't imagine after reading the many comments that koala will have 'excessive' optimism.
Not only did i dd...i also am doing 'big' riba. SOC would be 1000 mg..I've been doing since 10 week..1400 mg.
When I finish I will have been on tx for 22 mos.

[FlGuy]

The are many color variations to the treatment rainbow that can be viewed through the Gish (or many other) prism holders.  (BTW, I think Magnum is now in the Gish-Gang now, but wasn't for his Infergen extravaganza). Whether, it's double for the duration, double for a while and then more frequent Peg (ala Spaceman), big riba, waiting for the PI bus to come by, a maintenance Peg-only stretch or building an ensemble treatment there are a lot of options out there that might have merit.  Koala seems to be astute about what he's facing, including possible risks. My take is that while considering the risk/benefit ledger a person needs to know that he is really 'fully informed' and not just swayed by excessive optimism.

[ladywhy]

I double dosed peg for 55 weeks...blood work ok. I didn't advise my dr. I wanted this...he advised me. I am now back to 1 shot a week until Dec. BTW: My doctor is a hepatologist at a univ. hosp in a major city.

I am not advising you one way or another....just want you to know...it can be done and I wish you the best all the way to SVR...whatever you decide.

[comeagain]

"genotype 1B. Stage II fibrosis (from 2005 Biopsy). "
Thats three years ago remember I´m the walrus who in five years went to transplant.

And everybody is talking about telaprevir is gonna be here in 2010 , WTF does anybody knows about that.
Could be just rumors, it can very well take longer nobody can for certain say if its ever gonna be aproved.
My doc who is a researcher virologist specialist in infectious diseases author of articles  leading studies about HCV etc told me in may this year, when i asked him when he thought telaprevir will be aproved, he said this is off the record but never, and the reason for that was that sx was to big in comparing with benefits he specifically mentioned the rash.

Maybe its wise not to be to certain when recomending waiting for something that you don´t know for sure when its gonna happen if ever.

ca

PS I just wanna say I dont trust my docs predictions that much although hes good merits, hope hes wrong about telaprevir.
He has really said some strange things before such as he was certain I was stage 3
when the bx later showed stage 0 and he said he could predict that on my PK value which was 1.0  when I checked it, which is normal.

[geterdone]

Koala68, Just a curious question here, how much weight did you lose in the first 12 weeks?

jasper

[nygirl7]

"To be brutally honest, I think it's an absolutely HORRIBLE idea for a stage 2, 40 year old,"  

Whoa for once this has got me on the same page as Jim!  As someone who did a regular course of 72 weeks - I can tell you that the rewards just might not be worth the potential for problems here. 72 weeks of interferon did a number on me...and has left me with permanent autoimmune problems for the rest of my life. However as a stage 3 I did not feel I had any choice.

I wonder why you aren't looking to do at least a regular course of Infergen instead?  Infergen has has good results for geno1 RELAPSERS.
Or upping the riba factor a bit even would make more sense to me and then see where you are at week 4 - perhaps going to 72 on those results.

What week did you go UND at?  Little details like that might help us give you a better set of advice.  I had an EVR at week 4 (almost 3 log drop) however I was not UND until somewhere after 12 and before 24. THIS is why I did 72 weeks. It has been shown to help those who are not UND at week 4 have better odds of success. However it hasn't been proven to really assist those who have relapsed after a few months.  So double dosing AND extending seems a really drastic course when the other avenues have not been investigated first.

The consensus interferon (Infergen) is one option for a relapser and telepravir would be another - double dosing interferon for that long sounds like a last ditch effort and one that should be avoided at all cost if possible.

My docs never would have gone for it and both are extremely aggressive with treatment if you wish for them to be. Dr. Jacobson I don't believe ever would go for it in a million years but that is only my opinion.