20 replies to this topic

[kat73]

It sounds simple:  take less of a drug and you will get less impact from its side effects.  But if you think about it, why would this be so?  When you lower the dose of your TKI (after first having been stable at a low level of CML for some time, of course) you assume it will still have the same effect as a high one, right?  I mean, it hits the baddies just as effectively when it's thinned out, so to speak - otherwise, your PCR would show an upward trend, right?  So why would you expect the off-target hits to be any less at a lower dose?  They go right along with the targeted hits.  I'm probably not being very clear. 

 

I have a visit coming up and this is just the kind of question my onc does NOT ever want to talk about.  He gets mad at me instead.  And this visit I really, really want to talk rationally about finding a way to stop taking this drug soon, so I need cool-headed ammo.  He is very opposed to reducing dose, on principle.  But he definitely wouldn't let me quit altogether outside a clinical trial.  So I'm trying to see if it's worth it to go to battle over dose reduction.  If it could make a difference in the SE's, I would settle for that.  But I just can't see the logic.  Can anybody explain what I'm asking about?

[rct]

Yes.

 

The original Gleevec dose was 800 a day.  My Mrs lasted about three days on that.  600, then 400, because 400 was as low as they would go ten years ago.

 

From there it has been a steady procession of Oncs.  All of the big city teaching places don't have time for CML'rs, there are no more big papers to write and big discoveries to make, so they don't really want to bother with a person that can take a few pills and be done with it.  Just take a walk around Childrens Hospital and you'll see what they are really thinking about.

 

The small practice peoples don't know there are drugs besides Interferon, it only takes a couple different country oncs to find that out.

 

It's a long process finding someone that will work with you.  It isn't so much the science as it is the person.  Our current Onc only has a halfa dozen CML'rs, and he's at a pretty good sized regional hospital.  He is willing to work with Mrs on how she wants to do this.  PCR blipped up just a smidge and he wanted her to go from 200 a day to alternating 200/300.  It works like that, and she may still go to 200 a day again to see how it goes.

 

As far as side effects, she says the difference between 400 and 300 a day is big, 200 a day is huge.  I don't see her ever going back to 400 a day Gleevec, she'll prolly change meds if it doesn't work right anymore.

 

The "why" of it all is pretty simple.  Most docs say most problems are caused by non-compliance.  If the dose is 400 a day anything less is non-compliance, and their approval of such a dose is their participation in non-compliance.  It's a pain in the a$$ for them and nothing else.  Our last big name onc outside Philly was a teaching and experimenting and trials hospital and even he didn't want to mess with her dose.  He just didn't have time for it, but he was nice enough to point us at our current onc who is willing to work with her.

 

Good luck.  It is a tough road.  I don't know where you are but location can be a problem too.

[pammartin]

It is interesting, even Cleveland Clinic will agree to stop a TKI but they are not in agreement to lessen the dosage.  They are very concerned the lowered dose will create mutations.  I would think the lowered dose would be the best option as we all work through this stage of learning.

 

I admit I do not follow the updates as I should, but stopping a TKI has been proven to be successful in at least 50% if not higher in trials for CML patients.  What is the data for people who are on reduced dose and maintain an undetectable status for long periods of time. 

 

It may just be a different approach to the CML but I believe if one has to be on a TKI the lowest dose possible with less side effects has the highest advantages, including the mental health of the patient.

 

When Cleveland Clinic's Dr. Avani gave me her options they were in this order and she stated the third option she would not agree too without a meeting with the oncology department.

 

1. Begin Tasigna and continue 3 month PCR testing

2. TKI free and move to 2 month PCR testing

3. Lowered dose, but not without approval of the oncology team.

 

When I questioned her about the idea a lowered dose would not be advantageous, she was hesitant to even discuss the idea without her conference.  I did share I had met several people on the LLS site that are on low doses of TKI and unfortunately anything via the Internet was dismissed as potential fraudulent information. 

 

When I first began my journey in Oct of 2011 I was told missing one dose could create the potential for the CML to mutate.  I watched videos of Dr. Druker stating patients cannot miss doses because he was concerned with mutations and excelling to blast phase.  We have come very far in 5 short years.  I believe in time we will initially be given lower doses to treat CML, unless in blast phase from the beginning and gradually working up to a higher dose if needed.  This will create less side effects and what I consider a better beginning for treatment and the disease in general. 

 

Here is to hoping the trend continues.

[hannibellemo]

I go to Mayo - Rochester once a year (just like rct says, there are a lot of patients way sicker than I am that need their expertise) and am followed every three months at our regional cancer center.

 

When I developed a pleural effusion on Spyrcel 100mg. both locations were more than willing to work with me in lowering my dosage. Mostly because they knew I had a hard time getting used to Sprycel and I didn't want to go there again with yet another TKI.

 

I think the clinical thinking is changing for those who keep in the loop about these TKIs to "the lowest dose that works'. Seems like a no brainer to me.

 

For those not willing to change, I think liability concerns play a huge part and not knowing enough or having time to keep up with a disease and its treatment that they may only see a few times in their practice.

 

Good luck, kat!

[r06ue1]

It seems to me that a lower dosage would be the more likely for a mutation versus cessation.  I wonder if there is any data on both, what the mutation rate is for lower dosage versus cessation.

[kat73]

Thanks to all for your thoughtful comments.  I think Trey has illuminated that if there are mutations for resistance they are there from the beginning; they therefore don't emerge under a low dose, it is more like they are revealed.  So, if a person has been improving or stable at a very low level of disease for many years, they are a pretty safe bet for dose reduction.  My onc persists in disagreeing with this, but that aside, what I really want to explore is, is there any LOGIC to lowering dose to reduce side effects?  People report feeling tons better at lower dosage and I'd really like to try it.  But I don't understand how, if the drug is working on CML just as well at a low dose, then isn't it hitting off-target kinases just as much at a low dose, too?

[Antilogical]

kat - At a reduced dose, the drug is more diluted in your bloodstream, and as a result, fewer cells have a chance to encounter it and bind with it.

[kat73]

Thanks, Antilogical - so then I suppose the diluted drug is still enough to catch the CML which by this time is also sparser in the bloodstream?  If so, then I get it.  I'd sure like to find that sweet spot, like Trey has with long-standing undetectable CML, but on SE-less 200 mg Gleevec; or Scuba on 20 mg Sprycel and very low level CML, again, with no SE's.

[hannibellemo]

kat,

 

Interesting question. I had truly awful side effects with Sprycel for the first 4 - 6 months, to the point where I was concerned that I would die, Things started to get better around 4 months until one day I realized I felt fine (at least CML/TKI fine). The interesting thing about your question for me is at 50mg I don't feel any better than I did once I got used to 100mg.

 

Whatever, if your onc won't listen to you then you can always fire him/her and find one that will. Really, do you have to justify your desire to have a better quality of life? Scientifically, logically or any other ...ly?

 

What's the worst that can happen? Progression, definitely the worst, but unlikely; rise in PCR, possibly, but fixable; better QOL, possibly, but if not you aren't any worse off than now and you may be paying less if even if you don't feel any better. 

[simone4]

Pat, really, you thought you would die?  That's why I cannot go on Sprycel.

I see my onc. tomorrow for a retest of my last PCR which was  .4%.

I am still on 200mg. of Gleevec and the hives have not come back.

I will tell him that I will go back to 300mg. if I have to in order to get

my MMR back.

 

But what rct said about the difference in 300mg and 200mg is true

Huge difference in the way I feel.

I have gotten use to having my life back, so I can't go back to feeling

like I am going to die.  I am so sick of thinking about this I could scream.

 

 

 

[kat73]

Well, confusion reigns!     I see why oncs have trouble sorting us patients and our complaints (and beliefs) out.  One man's Gleevec is another man's Sprycel . . . I felt like Pat on Gleevec, Simone, and felt tons better on Sprycel, so go figure.  Anyway.  Thank you all for lots to think about and ways to martial my arguments.  I respect my onc - he's one of the top CML experts - and so I always feel that I need to bring science and logic to him, instead of tears, which I could easily do but won't.  I do agree with you, Pat, that it's not such a dreadful thing to at least try and see what a reduction might do for the ol' QOL.  Maybe it could pose a logistical problem for him - maybe he'd have to see me more often, insurance won't pay or he'll have to cobble up a code for reason or something - all possible problems for me, too, I guess.  I guess I've gotten greedy, or cocky - it's sort of like, OK, not gonna die of this, yay, but do I want to feel and look like this for the rest of my life anyway?  I don't want to be left behind the revolution when it comes, you know?  Left behind because I came in too soon.  In 10 years nobody will be taking this stuff, or at least not taking it forever and ever and ever and never getting off.  But in 10 years, I'll be old and nobody will care, least of all me.

[tazdad08]

 I mean, it hits the baddies just as effectively when it's thinned out, so to speak - otherwise, your PCR would show an upward trend, right?  So why would you expect the off-target hits to be any less at a lower dose? 

Here's my opinion... maybe I am wrong. I am a man, so it wouldn't be the first time. LOLOL... I truly believe the drs "throw" a predetermined generic dose at every one of us with cml. This dose is determined by the drug manufacture who profits off selling a higher volume of meds. Yes, some people need 100mg of a drug while others may do just as well on 25mg of the same drug. I cannot wrap my head around why a dr won't try a lower dose to see how you respond. I have "self medicated" for almost 4 years now. I did go too low at one time and became detectable again. I upped my dose and was undetectable within 60 days. I then cut my dose in half and have been undetectable since then. I am in no way giving medical advice... I'm only sharing my experience with my individual case. In a nut shell I am saying that we are mostly PROBABLY over medicated. Most of us would probably benefit well from less poison in our systems.

[rcase13]

I agree, I really wish more studies were done on dosing reductions. We need more information regarding lower doses.

[Antilogical]

Per my onc - there has been an uptick in discussions about dosages and quality of life at the CML meetings he regularly attends.  In fact, he adjusted my dose downward, saying that a deep response and stability meant that my CML was under control, and we could focus on quality of life.

[scuba]

Here's my opinion... maybe I am wrong. I am a man, so it wouldn't be the first time. LOLOL... I truly believe the drs "throw" a predetermined generic dose at every one of us with cml. This dose is determined by the drug manufacture who profits off selling a higher volume of meds. Yes, some people need 100mg of a drug while others may do just as well on 25mg of the same drug. I cannot wrap my head around why a dr won't try a lower dose to see how you respond. I have "self medicated" for almost 4 years now. I did go too low at one time and became detectable again. I upped my dose and was undetectable within 60 days. I then cut my dose in half and have been undetectable since then. I am in no way giving medical advice... I'm only sharing my experience with my individual case. In a nut shell I am saying that we are mostly PROBABLY over medicated. Most of us would probably benefit well from less poison in our systems.

 

Drug dose is determined through clinical trials. They graph response rates/patient numbers vs. dose and toxicity. The highest dose that can be "safely" tolerated for the maximum number of patients is determined through these studies, then various dose levels are examined. The dose that gives the best response without killing the patient is what becomes the standard dose

 

https://en.wikipedia...e-ranging_study

 

What they don't tell you is that within these studies, sub-populations of participants respond better or worse than the standard dose. A patient given 50 mg of Drug "A" will respond just as well as a patient given 100mg of the same drug - even though most of the patients in that cohort did not respond as well. In other words, the researchers already know that one size does not fit all - but it's simpler to prescribe one dose than try and figure out what is ideal on  patient by patient basis.

 

It is not correct that drug companies push higher amount of drug in order to make more money. It doesn't work that way. The cost of manufacturing a Sprycel "pill" regardless of amount of drug in each pill is pennies per pill. It's not true, for example, that Gleevec 400mg is twice the price of Gleevec 200mg. They are about the same price. They charge what they can because they can. 

 

Below is a link to an interesting article on what it costs to invent a new drug from concept through clinical trial and approval:

 

http://www.forbes.co...s/#61ab434f4477

 

Upwards of a Billion dollars can be spent to produce a new cancer drug. Typically $100 million is spent. And that includes "dry holes" - spending money on a drug that proves to be too toxic for human use or is proven not to work.

 

I have no affection for drug companies. Their profits are insane - but in our capital intensive system, I don't see a better way other than "greed" to drive the mother of invention. Take away the incentive for these companies to develop these drugs and innovation is likely to stop. There is a reason why the U.S. with only 5% of the worlds population is the number one economy. 

 

The key, I believe, lies in fostering competition in some way so more than one drug company is going after the same set of "customers". In this way, the answer lies in reforming the clinical trial process (not the science, but the bureaucracy) in order to reduce cost. Reform the patent laws so instead of a 20 year exclusion, maybe it's 10 years following drug approval or some other time period so that more competition can be brought to bear sooner. And the answer lies in public-private partnerships. Many of the drugs "invention" occur in labs associated with public universities. In the same way that the government created the interstate highway system, and - yes - the Internet (Al Gore reprise), government (that means "we the people") funds  lot of basis research that leads to these great drug breakthroughs. The public should share, in some way, the ultimate profit derived from a successful implementation of the research. Some of that does happen, but not enough.

 

Reducing drug cost, in one way or another, will necessarily involve increasing supply, increasing competition and decreasing cost of the clinical trial process. Another way is to reduce demand - but that is not practical since no one I know elects to get cancer. 

[Buzzm1]

It's not true, for example, that Gleevec 400mg is twice the price of Gleevec 200mg. 

Scuba, it is true that Gleevec 400mg is essentially twice the price of Gleevec 2 x 100mg; except there is a slight premium charged on the 100mg pills.  

http://www.goodrx.co...verride=Gleevec

 

The same applies for Sprycel: http://www.goodrx.co...CFYVCaQodklUOdQ

[scuba]

Scuba, it is true that Gleevec 400mg is essentially twice the price of Gleevec 2 x 100mg; except there is a slight premium charged on the 100mg pills.  

http://www.goodrx.co...verride=Gleevec

 

The same applies for Sprycel: http://www.goodrx.co...verride=Sprycel

 

Interesting .... that certainly wasn't true in my case when I took 400mg Gleevec and was reduced to 300mg (myelosuppression). The monthly prescription cost was almost identical.

 

Sprycel was the same way. I take 20mg Sprycel - 1/5th the normal dose and the price paid per month (via insurance) is also nearly identical to the 100mg version. 

 

Sprycel comes in 20, 40, 50, 70 and 100mg tablets. I had the 70mg version before getting prescribed both 40mg and then 20mg. All three were nearly identical in price.

 

So - I don't know what to make of the discrepancy. 

[mscl]

I was on 100 mg of Sprycel and now on 50mg to see if it keeps me undetectable without causing pleural effusion. Fingers crossed, only been on the new dosage less than two weeks. While my co-pay is exactly the same, the monthly cost is about $1,500-$2,000 less per month.

[Buzzm1]

I was on 100 mg of Sprycel and now on 50mg to see if it keeps me undetectable without causing pleural effusion. Fingers crossed, only been on the new dosage less than two weeks. While my co-pay is exactly the same, the monthly cost is about $1,500-$2,000 less per month.

mscl, according to this, there should be approx. a $4,500 difference:

http://www.goodrx.co...verride=Sprycel

[scuba]

mscl, according to this, there should be approx. a $4,500 difference:

http://www.goodrx.co...verride=Sprycel

 

Take a look here:

 

http://www.drugs.com...e-guide/sprycel

 

80mg, 100, 140 mg - all the same price (for 30 tablets)

and 50 mg is twice the expense of 70 mg. (for 60 tablets)

 

I have no idea what's going on or what price is "real". I suspect the prices quoted here are not what the insurance company's pay to acquire the drug for the patient. But it is strange that the discrepancy is so large.