I've read that in the lab, researchers are finding fenofibrate (Tricor) is showing inhibition of the growth of multiple myeloma cells. With that in mind, when my primary again recommends a drug for lowering cholesterol next week, I am thinking of suggesting fenofibrate instead of statins.
A couple of years ago, I took a statin for a few months and broke out in a severe rash all over my body. I've refused to restart them. So I'm wondering what to expect if I were to take fenofibrate for my cholesterol, and what sort of effect it might have on my myeloma. I am now in complete stringent remission and don't want to do anything to mess things up. Diet and exercise alone doesn't seem to lower my cholesterol.
Forums
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torimooney - Name: tori
- Who do you know with myeloma?: myself
- When were you/they diagnosed?: apr 2012
- Age at diagnosis: 64
Re: Fenofibrate (Tricor) and multiple myeloma
For those who wish to read more about the potential anti-myeloma activity of fenofibrate (Tricor), please see this related Beacon news story:
https://myelomabeacon.org/news/2013/10/28/fenofibrate-tricor-multiple-myeloma-clinical-trial/
The comments accompanying the article are worth reading as well as the article itself.
https://myelomabeacon.org/news/2013/10/28/fenofibrate-tricor-multiple-myeloma-clinical-trial/
The comments accompanying the article are worth reading as well as the article itself.
Re: Fenofibrate (Tricor) and multiple myeloma
This is indeed intriguing. I have been taking 40mg Lipitor/day for many years (well before I was diagnosed with multiple myeloma). Note that finofibrate is a generic name and is available as such. So cost-wise, it's painless to make the switch under my insurance.
I will discuss this with my GP and oncologist over the next couple of months. My bet is that they won't really have any insights into this wrt multiple myeloma one way or another....and will likely just say "try it".
Thanks for bringing this up Tori. I hadn't caught the earlier Beacon article on this.
I will discuss this with my GP and oncologist over the next couple of months. My bet is that they won't really have any insights into this wrt multiple myeloma one way or another....and will likely just say "try it".
Thanks for bringing this up Tori. I hadn't caught the earlier Beacon article on this.
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Fenofibrate (Tricor) and multiple myeloma
Note that I contacted one one of the doctors working on this trial. I specifically asked about the wisdom of switching from Lipitor to fenofibrate as a means to stave off progression to symptomatic multiple myeloma from smoldering multiple myeloma. In an nut, their reply was:
"....It is very reasonable to make the change provided your cholesterol remains under control. The side effects of fenofibrate are similar to Lipitor".
I'm going to do some more research with my own oncologist and GP and will consider making the switch after my next round of lab work (I believe in making tweaks to my supplement and Rx regiments only right after a lab test so that I can have an idea if a change I make is impacting my multiple myeloma numbers positively or negatively).
"....It is very reasonable to make the change provided your cholesterol remains under control. The side effects of fenofibrate are similar to Lipitor".
I'm going to do some more research with my own oncologist and GP and will consider making the switch after my next round of lab work (I believe in making tweaks to my supplement and Rx regiments only right after a lab test so that I can have an idea if a change I make is impacting my multiple myeloma numbers positively or negatively).
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Fenofibrate (Tricor) and multiple myeloma
So, after discussing this with the my lead onc and my GP, I just switched from Lipitor to fenofibrate. If I respond to it, the likely impact will be a reduction in my IgG levels (I'm IgG/Lambda). Will report back in a couple of months. No ill effects after 24 hours 
The other obvious question will be whether it will work as well as Lipitor for my HDL and LDL (I'm one of those guys where no amt of exercise and a supremely healthful diet can quite keep the cholesterol levels in check).
If you are considering this switch, always remember that I'm smoldering and not on any current multiple myeloma meds. So,I've got more leeway in experimenting with supplements and meds like this than somebody undergoing multiple myeloma treatment. No idea if it may potentially interfere with the mechanisms of the various multiple myeloma drugs, so proceed carefully and with your onc's guidance.
The science behind it is clever and is as follows:
Multiple myeloma cells are dependent on calcium (Ca2+) for their function. Specifically, Ca2+ is required for the function of the endoplasmic reticulum in which proteins, including immunoglobulins, are folded prior to their release from the cell. Multiple myeloma cells secrete large concentrations of immunoglobulins continuously and as result depend on mitochondria activity to replenish the Ca2+ levels in the endoplasmic reticulum as was shown in vitro in our lab. Fenofibrate has been shown to inhibit mitochondrial function resulting in inhibition of protein folding in the endoplasmic reticulum of multiple myeloma cells that leads to the induction of a stress signal known as the unfolded protein response and subsequently apoptosis. The effective anti-myeloma concentrations for fenofibrate are attainable in the clinical setting as they are in the same range as the effective concentrations for anti-hyperlipidemic effect. The investigators propose to evaluate fenofibrate therapy in multiple myeloma patients.
Thanks for the lead on this Tori!
The other obvious question will be whether it will work as well as Lipitor for my HDL and LDL (I'm one of those guys where no amt of exercise and a supremely healthful diet can quite keep the cholesterol levels in check).
If you are considering this switch, always remember that I'm smoldering and not on any current multiple myeloma meds. So,I've got more leeway in experimenting with supplements and meds like this than somebody undergoing multiple myeloma treatment. No idea if it may potentially interfere with the mechanisms of the various multiple myeloma drugs, so proceed carefully and with your onc's guidance.
The science behind it is clever and is as follows:
Multiple myeloma cells are dependent on calcium (Ca2+) for their function. Specifically, Ca2+ is required for the function of the endoplasmic reticulum in which proteins, including immunoglobulins, are folded prior to their release from the cell. Multiple myeloma cells secrete large concentrations of immunoglobulins continuously and as result depend on mitochondria activity to replenish the Ca2+ levels in the endoplasmic reticulum as was shown in vitro in our lab. Fenofibrate has been shown to inhibit mitochondrial function resulting in inhibition of protein folding in the endoplasmic reticulum of multiple myeloma cells that leads to the induction of a stress signal known as the unfolded protein response and subsequently apoptosis. The effective anti-myeloma concentrations for fenofibrate are attainable in the clinical setting as they are in the same range as the effective concentrations for anti-hyperlipidemic effect. The investigators propose to evaluate fenofibrate therapy in multiple myeloma patients.
Thanks for the lead on this Tori!
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Fenofibrate (Tricor) and multiple myeloma
If Tricor prevents proteins from folding, would it also enhance the effectiveness of Velcade?
The boron atom in bortezomib binds the catalytic site of the 26S proteasome[4] with high affinity and specificity. In normal cells, the proteasome regulates protein expression and function by degradation of ubiquitylated proteins, and also cleanses the cell of abnormal or misfolded proteins. Clinical and preclinical data support a role in maintaining the immortal phenotype of myeloma cells, and cell-culture and xenograft data support a similar function in solid tumor cancers. While multiple mechanisms are likely to be involved, proteasome inhibition may prevent degradation of pro-apoptotic factors, permitting activation of programmed cell death in neoplastic cells dependent upon suppression of pro-apoptotic pathways. Recently, it was found that bortezomib caused a rapid and dramatic change in the levels of intracellular peptides that are produced by the proteasome.[5] Some intracellular peptides have been shown to be biologically active, and so the effect of bortezomib on the levels of intracellular peptides may contribute to the biological and/or side effects of the drug.
The boron atom in bortezomib binds the catalytic site of the 26S proteasome[4] with high affinity and specificity. In normal cells, the proteasome regulates protein expression and function by degradation of ubiquitylated proteins, and also cleanses the cell of abnormal or misfolded proteins. Clinical and preclinical data support a role in maintaining the immortal phenotype of myeloma cells, and cell-culture and xenograft data support a similar function in solid tumor cancers. While multiple mechanisms are likely to be involved, proteasome inhibition may prevent degradation of pro-apoptotic factors, permitting activation of programmed cell death in neoplastic cells dependent upon suppression of pro-apoptotic pathways. Recently, it was found that bortezomib caused a rapid and dramatic change in the levels of intracellular peptides that are produced by the proteasome.[5] Some intracellular peptides have been shown to be biologically active, and so the effect of bortezomib on the levels of intracellular peptides may contribute to the biological and/or side effects of the drug.
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Eric Hofacket - Name: Eric H
- When were you/they diagnosed?: 01 April 2011
- Age at diagnosis: 44
Re: Fenofibrate and multiple myeloma
The question is way beyond my pay grade But I would imagine that would be a logical next step for the folks running the trial to explore, depending on what kinds of results they see in the coming months and years.
It seems like a typical path in drug development in multiple myeloma is to first evaluate its efficacy as a standalone item and then to experiment by combining it with other, currently available multiple myeloma drugs. As I think we all know, it is very rare that any of these drugs work that well by themselves. In fact, of all the dozens of drugs in the multiple myeloma trial pipeline, I think that SAR-50984 is one of the very few drugs that is showing any promise of being able to work as a stand-alone treatment. So, maybe they will find that fenofibrate doesn't do much by itself, but could help with other drugs? Or, that it just simply improves your cholesterol and only increases multiple myeloma cell apoptosis in mice
But I would imagine that would be a logical next step for the folks running the trial to explore, depending on what kinds of results they see in the coming months and years.It seems like a typical path in drug development in multiple myeloma is to first evaluate its efficacy as a standalone item and then to experiment by combining it with other, currently available multiple myeloma drugs. As I think we all know, it is very rare that any of these drugs work that well by themselves. In fact, of all the dozens of drugs in the multiple myeloma trial pipeline, I think that SAR-50984 is one of the very few drugs that is showing any promise of being able to work as a stand-alone treatment. So, maybe they will find that fenofibrate doesn't do much by itself, but could help with other drugs? Or, that it just simply improves your cholesterol and only increases multiple myeloma cell apoptosis in mice
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Fenofibrate (Tricor) and multiple myeloma
Multibilly - I don't think what you're suggesting about single-agent activity is necessarily true. Drugs like the imids and proteasome inhibitors do have noticeably single agent activity, as do older drugs like melphalan and Cytoxan and, of course, dexamethasone. I think the anti-CD38 monoclonal antibodies do as well.
Elotuzumab and the HDAC inhibitors like panobinostat and Zolinza, on the other hand, don't have much single-agent activity, and in the case of Zolinza, that also led to it not having all that much activity in combination with Velcade (although it did give Velcade a little bit of a boost).
So while single-agent activity against myeloma is getting a bit less common with some of the newer agents, it's not at all rare among anti-myeloma agents as a whole.
Elotuzumab and the HDAC inhibitors like panobinostat and Zolinza, on the other hand, don't have much single-agent activity, and in the case of Zolinza, that also led to it not having all that much activity in combination with Velcade (although it did give Velcade a little bit of a boost).
So while single-agent activity against myeloma is getting a bit less common with some of the newer agents, it's not at all rare among anti-myeloma agents as a whole.
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JimNY
Re: Fenofibrate (Tricor) and multiple myeloma
Jim,
Point taken and you are obviously right. I think a talk I heard from Dr. Durie in recent months relative to some of the new drugs in the pipeline and how SAR650984 stood out in its standalone efficacy was stuck in my head.
Point taken and you are obviously right. I think a talk I heard from Dr. Durie in recent months relative to some of the new drugs in the pipeline and how SAR650984 stood out in its standalone efficacy was stuck in my head.
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Fenofibrate (Tricor) and multiple myeloma
Hi Multibilly, I am asking my GP to switch me from Lipitor to Tricor on Friday after reviewing this thread. Did the switch have any effect on your numbers. Best. Terry L.
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terryl1 - Name: Terry
- Who do you know with myeloma?: self
- When were you/they diagnosed?: August 10, 2011
- Age at diagnosis: 49
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