18 replies to this topic

[thatguy]

So it's common practice that if a patient isn't having desired response to treatment, typically the dose is increased before a switch - often times with success...

Therfore we can ascertain that more drug concentration produced the result. Makes sense to me.

What then of the larger-than-normal patient, not responding optimally. Is there not added blood volume and tissue to saturate, along with a likely higher content of foods and liquid in the diet, further diluting the plasma/drug content?

I ask based on my size: 6'4", 285. My latest goal is lose the weight and hope for desired outcome, because again, I'm at the highest dose of the stuff, and I've experimented with different lifestyle factors. And my interesting, persistent lack of side effects has me on the verge of concluding I'm simply not getting enough drug.

Anyone care to share their response description, and what their physical size is?

[AdamJ]

That is an interesting question, Thatguy. I am also quite curious to know if body size is a factor impacting the drug absorption. For reference I am 6' and just under 170 lbs and I responded pretty quickly. I had assumed that my response was related to my very low WBC at diagnosis, but it could be related to your theory. My FISH test at diagnosis was about the same as yours, but my WBC count was only 17,400.

[tiredblood]

I'm overweight and have had the best possible response to therapy, along with non-life threatening side effects.

[jjg]

Back when I was on gleevec I had a plasma test. I was taking 600mg and while I'm not tiny, 5' 9.5", I'm definitely lighter than average and weigh less than half what you do. Anyways my plasma test came back just within the therapeutic range even though I was taking what is considered to be a high dose. There are many factors that affect absorption, weight is probably one but not the dominant one.

 

You are doing ok but you want to do better. You could ask if there is is a plasma test for Bolsulif but it's not going to help if you've already maxed out the dose. It's great that you have no side effects as from what I read 500mg has really knocked some around.

 

Thb the CML is kinda under control (& sorry if this comes across wrong) so loosing excess weight is probably the thing that will most improve your health in the long term and of course we've all got plans to be around for a long time. It would be cruelly "funny" if loosing weight brought you more tki side effects.

[Sandrea]

Therfore we can ascertain that more drug concentration produced the result. Makes sense to me. What then of the larger-than-normal patient, not responding optimally ... And my interesting, persistent lack of side effects has me on the verge of concluding I'm simply not getting enough drug. Anyone care to share their response description, and what their physical size is?

 

Thatguy, I also began to think about it when I saw that my response was slow. I have mild side effects too and I never had a myelosuppression, despite the fact that I was on hydroxyurea for 2 months. My height is 170cm (5'6"?), and my weight increased by 44lb in the first six months of receiving the imatinib and became 220lb. I even found some confirmation of this theory, here is a quote from the instruction: "Typically, clearance of imatinib in a 50-year-old patient weighing 50 kg is expected to be 8 L/h, while for a 50-year-old patient weighing 100 kg the clearance will increase to 14 L/h." www.imatinibrx.com/..._Tablets_PI.pdf

And here is quote from another article: If compared to patients with low body mass index (< 18.5-25), patients with increased body mass index (> 25-40) at diagnosis who received imatinib, showed a significantly longer median time to reach CCyR (6.8 months vs 3.3 months, p=0.01), a reduced rate of MMR (77% vs 58%, p=0.01) which was also achieved in a longer median time (29 months compared to 14 months, p=0.03). http://www.bloodjour...ent/120/21/2784

 

P.S.  Interestingly, I achieved MMR exactly in time specified in this article - at 29 months
(11.17.2017  PCR  0.057% IS)

 

related threads:

Body Size's effect on level of G response

Gleevec Blood Level Concentrations

 

Edited by Sandrea, 30 January 2018 - 07:07 AM.

[chriskuo]

Did you weight increase while on any of the TKIs? Fluid retention is a common side effect.

I am on 300mg bosutinib and I have had to strictly limit my salt intake and take furosemide to minimize the
fluid retention.

[cmljax]

I am 5'10" and 160 - 165  versus 170 - 175 at diagnosis.  Being on Tasigna has not caused me to gain or lose weight, so the CML actually took the weight.  My response has been very fast but I really don't know if it has anything to do with weight.  In response to CML, I eat a much healthier diet and have doubled my cardio workouts.  I want to do everything in my power to be as fit and healthy as possible to help my immune system be as strong as possible.

 

I reduced dose 25% in early March because of multiple skin cancers and precancerous lesions that started about a month after I started taking Tasigna. These skin issues have slowed dramatically since the dose reduction and my weight has held steady. My response 1 month after dose reduction continued to improve from .006% to <.003% IS

 

Sandrea's article is surprising to me, but perhaps body mass does have something to do with response.  If so, losing weight would be a good idea.  If not, losing weight would be a good idea because all of the TKI's have potential cardiopulmonary effects and a couple have even been shown to increase the risk of type 2 diabetes.

[thatguy]

Did you weight increase while on any of the TKIs? Fluid retention is a common side effect.I am on 300mg bosutinib and I have had to strictly limit my salt intake and take furosemide to minimize thefluid retention.

Yes Chris, I gained about 25 lbs but I fully blame my lack of activity and ravenous gluttony in recent months.

[thatguy]

Thatguy, I also began to think about it when I saw that my response was slow. I have mild side effects too and I never had a myelosuppression, despite the fact that I was on hydroxyurea for 2 months. My height is 170cm (5'6"?), and my weight increased by 44lb in the first six months of receiving the imatinib and became 220lb. I even found some confirmation of this theory, here is a quote from the instruction: "Typically, clearance of imatinib in a 50-year-old patient weighing 50 kg is expected to be 8 L/h, while for a 50-year-old patient weighing 100 kg the clearance will increase to 14 L/h." www.imatinibrx.com/..._Tablets_PI.pdf
And here is quote from another article: If compared to patients with low body mass index (< 18.5-25), patients with increased body mass index (> 25-40) at diagnosis who received imatinib, showed a significantly longer median time to reach CCyR (6.8 months vs 3.3 months, p=0.01), a reduced rate of MMR (77% vs 58%, p=0.01) which was also achieved in a longer median time (29 months compared to 14 months, p=0.03). http://www.bloodjour...ent/120/21/2784

 

Interesting! Thank you.
I'm honestly debating on adding small amounts of grapefruit juice (disclaimer: it is forbidden) to try to amplify my dose in the meantime. Down 4 lbs this week though so far.

[thatguy]

Back when I was on gleevec I had a plasma test. I was taking 600mg and while I'm not tiny, 5' 9.5", I'm definitely lighter than average and weigh less than half what you do. Anyways my plasma test came back just within the therapeutic range even though I was taking what is considered to be a high dose. There are many factors that affect absorption, weight is probably one but not the dominant one.

You are doing ok but you want to do better. You could ask if there is is a plasma test for Bolsulif but it's not going to help if you've already maxed out the dose. It's great that you have no side effects as from what I read 500mg has really knocked some around.

Thb the CML is kinda under control (& sorry if this comes across wrong) so loosing excess weight is probably the thing that will most improve your health in the long term and of course we've all got plans to be around for a long time. It would be cruelly "funny" if loosing weight brought you more tki side effects.

 

Exactly. That's very interesting too... so common sense would say a guy like me could easily be beneath that threshold... thanks for sharing.

You're right about the other stuff. And honestly, for once im not even really stressed, as I was skeptical of my huge drop to .0445, at a new lab, being accurate to begin with. I looked at these recent results as likely the more accurate, as they're more in line with my trend at the old lab. My doc on the other hand called me personally and was like "its up, I'm calling the transplant dr!"

Ugggh, its exhausting. This in turn stresses my wife out who, well, in turn stresses me out, and back into the cml rabbit hole. Junk

[thatguy]

That is an interesting question, Thatguy. I am also quite curious to know if body size is a factor impacting the drug absorption. For reference I am 6' and just under 170 lbs and I responded pretty quickly. I had assumed that my response was related to my very low WBC at diagnosis, but it could be related to your theory. My FISH test at diagnosis was about the same as yours, but my WBC count was only 17,400.

Just trying to weed this CML garden, man... I'm eliminating what variables I have control of - which may likely prove to be frivolous. That's great for you, that's probably the lowest wbc I've heard of on here! Envious!

[Sandrea]

I'm honestly debating on adding small amounts of grapefruit juice (disclaimer: it is forbidden) to try to amplify my dose in the meantime.

 

I have already tried grapefruit juice for ten months (for increase the concentration of imatinib) but it didn't help me, perhaps it even harmed me. In this article "Can grapefruit juice decrease the cost of imatinib for the treatment of chronic myelogenous leukemia?" the concentration of imatinib was even lower in two men after grapefruit juice in fact...

My doc on the other hand called me personally and was like "its up, I'm calling the transplant dr!"

 

We were diagnosed almost at the same time, but my numbers are worse than yours, and my doc is absolutely calm, she even keeps me on 400 mg Imatinib still.

[thatguy]

I am 5'10" and 160 - 165 versus 170 - 175 at diagnosis. Being on Tasigna has not caused me to gain or lose weight, so the CML actually took the weight. My response has been very fast but I really don't know if it has anything to do with weight. In response to CML, I eat a much healthier diet and have doubled my cardio workouts. I want to do everything in my power to be as fit and healthy as possible to help my immune system be as strong as possible.

I reduced dose 25% in early March because of multiple skin cancers and precancerous lesions that started about a month after I started taking Tasigna. These skin issues have slowed dramatically since the dose reduction and my weight has held steady. My response 1 month after dose reduction continued to improve from .006% to <.003% IS

Sandrea's article is surprising to me, but perhaps body mass does have something to do with response.
If so, losing weight would be a good idea. If not, losing weight would be a good idea because all of the TKI's have potential cardiopulmonary effects and a couple have even been shown to increase the risk of type 2 diabetes.

Yeah Jax, I'm really sorry to hear about the skin cancers, my biggest fear at this point is that a second cancer will arise. How are you handling all that?

[cmljax]

The skin cancers, though not life threatening, were a real shock particularly right on the heels of my CML Dx. It was a hard 3-4 months emotionally as I had one confirmed biopsy after another - my legs and arms look like war zones.  But, now that skin lesions have subsided substantially it's a lot better emotionally. I just hope it stays that way - if they start coming back I will definitely switch TKI's

[thatguy]

I can't imagine. Truly sorry you've had this hell to deal with, and glad you've been aware and proactive in having them checked out early.

I always hear the City of Hope commercial on the radio featuring the Dr. talking about switching his focus from killing breast cancer to finding what processes in the brain prevent cancer from forming throughout most of our lives. While I hope that is a successful journey, it does worry me to wonder "is my body back in control now?"

Anxiety is mountain for me, personally.

[tazdad08]

I remember seeing some study of patients eating grapefruit with their meds to increase absorption. I don't have a clue what the outcome was, but may be something to look into. To the best of my knowledge we are told to avoid grapefruit because it increases absorption.....so, it does make some sense to eat if more absorption is needed. But again, I didn't follow the study and have no idea of was found from it.

[Buzzm1]

My own experience with grapefruit, while on a greatly reduced dose of Gleevec, was very painful. My achilles tendon felt as if gout had set in; it took roughly two weeks to resolve. My understanding is, it isn't that grapefruit increases absorption, it's that it increases the length of time that the TKI remains in your system. Admittedly, I overindulged in grapefruit at that time.    Be very careful.

[thatguy]

So here's a question maybe somebody can answer. Although grapefruit increases the length of time it is in our system, and hence the risk of over dosing, is it "usable" at that point or just kind of floating around not being absorbed and therfore not of therapeutic benefit?

I recall a time on Tasigna when I washed down my pm pills with a Fresca after several diet Dews on the golf course, and the following day on the golf course was miserable. Pounding headache, watery eyes, pulsing vision, miserable... so yeah, good reminder, Buzz.

[Trey]

If there is a difference, it would be more due to blood volume not fat volume.  Adults generally have about 5 - 7 liters of blood, and children have much less.  Height and muscle mass are more of a factor than fat weight.  Men generally have more blood than women.  And an even bigger factor is altitude where you live, which can add over a liter at high altitude. 

 

The TKI drugs only target white blood cells (WBCs), which make up .1% of the total blood volume.  Red blood cells make up about 45% of blood volume, with the remainder plasma.  Of the .1% blood volume which is WBCs, most are "worker bee" cells which cannot reproduce, so are not a target of the TKI drugs.  So we are down to only about .001% of blood volume which is dividing WBCs which the TKIs can target.  If the patient is CCyR or better, that volume of target cells (leukemic WBCs only) is down to about .000001% (wild guess) of blood volume.

 

So is "personal volume" an issue?  Maybe just a little.  But other factors have much more of an impact on how efficiently the body uses the TKI drug. 

 

But I would think being overall healthier would have a greater impact on how the body deals with any disease.  So start moving and lose the weight. 

 

http://tech.snmjourn...nt/35/2/55.full

Edited by Trey, 22 May 2017 - 09:26 AM.