Abemaciclib Verzenio for Stage IV
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I am here to report after being on reduced dose of Verzenio to 100mg for about 1 month now has significantly reduced the gastrointestinal side effects and I am feeling better for sure.
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My advice: To delay CDK4/6-inhibitor resistance, take Claritin (I’ll start this week); don’t fast (I did and it backfired).
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Luce, thank you for sharing the link. Someone posted it on Facebook today with the same comment that Claritin could be used instead of HCQ because it also inhibits autophagy, but I've not been able to find the article that spells out the loratadine/autophagy connection. Do you happen to have a link handy? Thank you so much!
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i have no studies linking antihistamines with autophagy inhibition either but posted her FB recommendation here because there is a large population study linking antihistamines with survival benefit. some of that benefit may well be due to autophagy inhibition. and claritin or clarinex (desloratadine) do not seem to interfere with cdk4/6 inhibitors, so may be a safe drug to add. i'm planning on adding one or both within a week or two.
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Luce, we seem to be in the same facebook group! Thanks for sharing over here as well.
I did a bit more digging and found not a paper, but a patent application linking loratadine with autophagy: https://patents.google.com/patent/WO2018003829A1/e...
It even mentions that most studies combining autophagy inhibitors with anticancer treatments use chloroquine and hydroxychloroquine (like the researchers in your posted study did) but they found other alternative agents, including loratadine, that can play the same role.
I've been taking loratadine almost since my diagnosis, based on the population study you mentioned, but I'm excited to hear that it can perhaps prolong the activity of CDK 4/6 inhibitors (I'm on Ibrance/letrozole). I have a 7-year old daughter, I need to wring every possible month out of each treatment!
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Hi, My real name (under which I go on FB) is Esther Burns, by the way. Luce is an alias to protect privacy. (I am assuming piggy99 isn't your given name, either.) I no longer care about privacy in this group, though. How much loratadine do you take? I want to add it asap. I wish more patients, scientists, and doctors would put more time into trying to figure out combinations to enhance targeted therapy, and/or make response more durable. Verzenio has been a life-extending drug for me, with side effects I consider minor given the big picture, and I want to extend its life in me! I have some ideas but they may clash with some of Verzenio's mechanisms, and I don't have much room for error/course correction since one cannot do without a lung. So complicated! Anyone scientifically trained in this group here that I could bounce my ideas off? Thanks!
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Luce, I am very interested in this subject (which is why I have been following you and curious on this thread). I am taking loratadine daily because it supposedly helps with certain kinds of pain related to cancer and/or treatment. I recently saw an article about the retrospective study (Sweden?) about prolonged survival. Are you reading the book "How to Starve Cancer" by Jane McClelland? I'm not finished with it yet but lots of good info about meds/supplements to help treatment last longer. There's lots of them but I need to finish the book and write them down depending on my situation. So far I am taking berberine.
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Luce and Piggy, I'm very interested to read about loratadine and autophagy. Thank you for the links. What dosage is recommended? (Luce, I love your real name. My little sister is Esther--my mother let me pick her name, and so I chose Esther. She loves it and so do I.)
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Yes, I read Jane's book last summer. Her recommendations do not take newer therapies---targeted and immono--into account, though, so may clash. Especially the supplements, which are even less studied, interactions-wise. By the way, while she is clearly a smart women and helping many, she is very control-freaky and usually does not allow my posts, although they all adhere to her guidelines: repurposed drugs only. I'll write a post soon about my hopes and concerns for each supplement and repurposed drug in combo with Verzenio, Needless to say, it is EXCEEDINGLY complicated. And i have no margin for error; were I bone-only, I would feel freer to just explore without all this mindboggling and exhausting research first.
Schnauzermom: I love that your mom let you name your sister! Had mine allowed that, I'be be named Edaby. Or maybe piggy99.
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I've been reading a bunch about loratadine, and it appears that the dosing is between 10 to 40 mg. I don't know what frequency.
There's also been some interest in the H2 Antagonists like ranitidine, so, yes, I'm taking that too. After finishing the last article, I'm going to stop taking ranitidine for now, because I am on Gemzar.
http://dar.aucegypt.edu/bitstream/handle/10526/520...
Yes, this is someone's thesis, but looked so interesting.
https://www.sciencemag.org/news/2017/12/old-drug-a...
This is about antibuse.
https://breastcancer-news.com/2016/07/14/Heartburn...
https://www.frontiersin.org/articles/10.3389/fimmu...
No guidance on dosing, but cool data on B cells
http://www.jimmunol.org/content/194/1_Supplement/2...
https://www.tandfonline.com/doi/full/10.1080/21624...
Dosing guidance, but it is fancy. Ranitidine while on Gemzar seems a no-go.
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There is also a group called Repourposed Drugs for Cancer Treatment (on fb) where people post freely. Jane posts and replies to posts on there and there is a woman named Jana Downing who is very knowledgeable. That group is pretty active with people who are doing the protocol.
Glenn Beck is going to interview one of the guys involved with the Israel study on his radio show tomorrow.
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yes, thanks, great resources and links. problem is, no one (on these forums, for example) has figured out yet how to combine repurposed drugs and supplements successfully with cdk4/6 inhibitors. i am trying to do that for myself (planning on using repurposed drugs--antihistamines, say, or antimalarials, or perhaps disulfiram, etc.) to block autophagy, say, and mTOR signaling) but the science is devilishly complicated since cdk 4/6 inhibitors work by several mechanisms, some poorly elucidated. and i certainly don't want to interfere with those mechanisms. but the future of cdk 4/6 inhibition is definitely in combining drugs, especially to avoid/delay resistance. i am mostly worried that the substances that inhibit mTOR- and pi3k-signaling also happen to be powerful antioxidants, and verzenio puts cancer cells into senescence (false or permanent, depending on if you are on monotherapy or estrogen blockers: in monotherapy, the senescent cells rapidly return to cycling once the drug is withdrawn or resistance has built) via ROS. but too much ROS leads to cancer cells adapting and mutating. it's all very confusing. (to me, at least. i have a 9th-grade education.)
i submitted a query to global cures; i'll let you know their response. also, i'll be discussing this with my oncologist soon. i have to get my science straight first, though: i need to work my way through about 50 studies, and hundreds of FB posts.
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You're right, it is very complicated and therefore discouraging. I have to take breaks from the constant reading which is why I haven't quite finished the book yet.
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Jane's book is good (but/and hard to read, the technical second part) but a different issue. I am not trying to block all of cancer's metabolic pathways. I am trying to extend the life of Verzenio, and thereby mine. For that, I am studying the newest papers on CDK4/6 inhibitors (which Jane unfortunately knows nothing about), then look at what might work to block the mechanisms of Verzenio resistance (for example, enhanced pi3K signaling; autophagy). THEN i try to figure out if whatever substance i am hitting on that may do these things may not somehow interfere with verzenio's mechanisms (inducing senescence via ROS, for example). i'll bounce all of this off my oncologist next week. my naturopathic oncologist has quit on me; this is over her head. I also wrote to Global Cures and shall report back. and, yes, i encourage taking long breaks from all this if you can. I am on a different timeline: I have been on Verzenio for a year now. And I was actually dying when I went on it.
Jane's repurposed drugs approach, I MAY try when I run out of other options. i am really not a big fan of statins and antibiotics, for a number of reasons (one that even former antibiotic use seems to negatively impact response to immunotherapy, for example), but i also see her point.
Some women on jane's or COC's protocol are on palbo, according to FB; but I don't know anyone on verzenio on it.
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Hi Miaomix and Chemokaze,
Sorry I haven't posted in a while, been busy dealing with some crappy side effects. My Hemoglobin has been slowing decreasing over the past several months. When I stopped everything on Dec 22 the onc thought things might go back to normal. No such luck. On Monday of this week he got the test results back from my latest blood work- did more extensive such as iron and procrit readings and found that my Hem was 6.6. Off I went to get two pints. That brought me back up to about 10 and my WBC and grans were normal.
My procrit level was low so we are going to stick a needle in me with that starting next Wednesday. He feels that will help offset what the Xeloda might do to my Hem.
However, as I previously reported, I went through some serious body pain when I briefly went back on Verzenio before quitting altogether. My TM's have now risen to 1200 and I have a lot of pain in my muscles and joints. The blood transfusion helped but I am still forced to take some sort of pain med to sleep sometimes. I feel awesome and free of pain when I take Hydrocodone but it makes me sort of groggy the next day with no energy. So I am going to just try some Tylenol or Aspirin to see if that helps. The pain is not as severe as before but still interfering with my sleep.
Also, I wanted to ask if the pain I feel in my muscles in my legs and calves is anything anyone has experienced. I know I have had sciatica before so I am stretching to see if that helps. Is pain management just what I have to deal with going forward?
The onc keeps telling me that my tumors are tiny but they seem to be wreaking havoc on me anyway. The Foundation One test has not come in yet. Since my Hem was up I started on the Xeloda yesterday. He is starting me on a half dose since I seem to react so strongly to some of these drugs.
Ah, the party. Nope. Decided it's just too much work for me. So, we are going to Flemings for dinner and some friends are joining us. I can wear my fab dress and the jacket my husband got me and not have to expend what little energy I have running around entertaining everybody.
I gave notice at my job on Tuesday. My poor little boss who is a 93 year old lawyer cried and told me he loved me. Hated to see me go. But I was only working to have some social outlet and extra money to put into house renovations. I want to spend my time doing things I enjoy and not fixing everybody else's problems. As I approach 77 years old (scary) on February 17th I figure I have done enough fixing for others. Time for me.
Even though I have moved on to Xeloda I will stop by and update. Perhaps it will be helpful to see what the results are if others have to transition away from Verzenio.
Prayers for all.
Chats
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hi Chats! Sorry to hear about your travails and relieved by the improvements brought about by the transfusion. As far as pain management is concerned, in addition to a 12.5 mcg fentanyl patch, I have found great relief from the intake of antioxidants, such as good quality Omega 3 fish oils, daily supplements of magnesium, potassium and calcium. To basically use alkaline foods and supplements to counterbalance the pain caused by the lactic acid created by the cancer. It’s been working extremely well to the surprise of my pain management specialist.
I totally get your decision to manage your energy by focusing on your needs instead of constantly pleasing others. Something that I'm reminded to observe at times when I find myself exhausted and drained by my social engagements. I applaud your decision to quit working and to concentrate on your health....
Being on xeloda is still the best treatment for meso far. I hope you too benefit from it. I particularly love the week on and off part of it.
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Luce, I take 10mg of Claritin (the normal allergy dose). It may or may not be optimal, but at least the Swedish study was presumably done with the regular allergy dose, so it must have an effect at that level.
Claritin has a huge volume of distribution, which means the organ concentration is much higher than the plasma concentration. Additionally, because it's a cationic amphiphilic molecule, researchers suspect that it might accumulate in tumors because of their acidic microenvironment, so it's quite possible the tumor concentration reaches pharmacologically relevant levels with the 10mg/day dose.
Regarding research - when I was diagnosed I cried for days because I realized that this was a situation I wasn't going to be able to research my way out of. Didn't stop me from searching and reading for weeks and weeks, looking for something that I could do to improve my odds. I don't think that THE CURE is out there, hiding in plain sight or hidden by big pharma just waiting for us to find it. But I do think, like Luce mentioned, that there are things we can do to make the treatments that we have work better or longer, buying us a couple of months here and a couple of months there until hopefully something new and big comes along.
Although the universe of ideas out there is big, the universe of feasible things to try outside of clinical trials is much smaller. As lay people, the only "agents" we realistically have access to are drugs already approved for other indications, and even out of those some are easier to access than others. From that universe, the ones that stood out to me as having shown some promising results in humans are doxycycline, loratadine, aspirin, copper chelators/Tetrathiomolybdate, statins and disulfiram. There are others, like metformin and ACE-inhibitors (blood pressure drugs like captopril) that have shown some promise in the lab, but don't seem to have sufficiently convincing human data yet.
Of those, only loratadine and aspirin are over the counter, and since they have both shown positive survival results in large population studies and have been used in cancer patients for decades, I felt that FOR ME and my risk tolerance level they were OK to add to my treatment. I also found the reseach on resolvins and their role in mopping up cancer cell debris, preventing them from propagating metastatic signaling to be quite compelling, so I added some fish oil to my aspirin regimen (aspirin promotes the syntesis of resolvins from fish oils).
To go further, I would have to convince my doctor to prescribe some of the other drugs, and I'm not sure that he would. I'm not sure I have the personality to push for it, either, although that might change if the current treatment stops working.
I would love to see some funding going to the NIH to initiate some drug-repurposing trials. I think the for-profit pharma research model is great for certain things like pushing the envelope on new and complex mechanisms that can't be done on the cheap, but it's not the right model for everything (Disclaimer: I'm an organic chemist by training and I worked in drug-discovery research for a decade and a half). When a pharma researcher sees, for example, that loratadine synergizes with palbociclib, they don't think "great, let's tell the company to run a trial". They think - let's start a research program to find a new, better "loratadine-like" molecule that we can actually patent and turn into a blockbuster drug. Clinical trials are expensive, and corporations - pharmas and biotechs included - are in the business to make money. I think it's myopic to believe that all "societal good" is able to and should come from capitalist enterprises - there are some things that would be much better served through non-profit, public-funded efforts. Repurposed drug trials are one of the many examples. Alas, NIH funding has narrowly escaped a big funding cut, and I don't see taxpayer dollars being poured into these types of efforts any time soon.
I don't really know where I was going with this - just that it's hard to save your own life, whether or not you have a scientific background, and I wish there was more help out there. Thanks to all of you who keep trying and sharing ideas.
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Piggy: thanks you so much for your informative post! i am seeing my oncologist tomorrow and was planning to ask for a prescription for desloratadine (5mg, although i know people who take 5 mg seven times a day--spaced out-- for breast cancer. reasoning being the doc who wrote up that swedish paper recommends dosing so high in metastatic disease to try to speed up the process of it working since, yes, it seems to accumulate in tissue and on a low-dose, has been shown to take as long as a year to make a difference.) if i can't get him to prescribe it or if my insurance won't pay, i'll go for the over-the-counter you are taking. i read that deslo is the activated form, so easier for the body to utilize and potentially less side effects. some people speculate that metabolites from activating loratadine might have discreet anti-cancer benefits, though. i am hoping this particular drug will help delay verzenio resistance by blocking autophagy.
i'll go for metformin also, as that appears to inhibit mTOR, amongst other mechanisms of action. also, it dials down IGF-1. sure, i could do that through diet--no dairy, say--but my diet is relatively healthyn already and i don't want to restrict too many of the few foods i still enjoy (cream in my coffee, say).
it's all very confusing since mTOR inhibition induces autophagy (and presumably vice versa) but/and both are verzenio-resistance routes.
yes, you are of course right: i am not going to find the cure by doing all this research. but i do believe that these very new drugs we are on will in future NOT be used as monotherapy or only with endocrine-therapy but in combinations, and partly for the very reason i am doing this research: to delay resistance.
i agree with you 100% on your lucid explanation of how drug development works. i see that in my oncologist every time i talk to him: ready to suggest cutting-edge cancer drugs that happen to be very toxic (i'm looking at you, everolimus!) but unwilling to look at repurposed drugs that MAY do much of the same thing, and much, much cheaper. it's just not part of his training or mindset.
thanks for the aspirin and fish oil advice! i am taking both (the baby aspirin as of fairy recently, since aspirin had caused me bruising in the past (when i was taking it for a bit to try and prevent recurrence) and dr. nasha winters scared me off it by calling it "metabolic poison," so i stopped for a while) but not together; now i will. i am also thinking about taking an aspriin-dipyridamole combo, but have to look into that further.
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Piggy and Luce,
Thank you so much for your insights on all of this information. I started taking 10 mg of loratadine last Friday based upon your earlier discussion. ( I did read the Swedish study and also a Danish study which dealt with non-small cell lung cancer. The loratadine seemed promising in both.) I do not have pharmacological expertise that you both have, and I will read your postings with great interest! Again, sincere thanks to both of you!
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Piggy and luce, thanks for this discussion. Near the beginning of all this for me I asked my oncologist about aspirin for pain relief. He said to only take one occasionally and only occasional ibuprofen also. He said use acetaminophen but to stay under 1,000 mg a day due to liver mets. I've been reading here about aspirin and want to try it so I'll ask him again. I don't remember why he didn't want me to have much aspirin. I think my platelets, etc. are decent. He did say fish oil was okay so I take that daily. I've been taking loratidine for years and I still do. My oncologist is interested in using existing drugs. Last time we talked, we both mentioned antabuse and metformin as being interesting so maybe he'll take another look at aspirin. Normally I would take what I wanted, but I have been surprisingly compliant since my dx because all this is waaaaay out of my league.
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Don't know what you think about alternative med. but one practitioner in Philippians Recommend dissolving your aspirins in water first. It's suppose to be easier on your stomach. He said aspirin allows your Tcells to recognize cancer as "nonlife' or other which doesn't belong. So for what it's worth, I'm sharing the info.
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Cost of V: after no co-pay last year, the specialty pharmacy called in January and wanted $10 for a 4 week supply. Apparently, the Lilly program provides the first 3 months free which I didn’t know. I’ll have private drug insurance until I go on Medicare in 2 years. Not sure what will happen to the price at that point, if I’m still on it...
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Hi all, I am the newest in Abemaciclib (verzenio) community. Thank you for providing lots of information that one can dream about. I will start Fermara +Abemaciclib and a mystery pill which is a phase 1 trial from lilly company in addition to that, on March 7. this pill will be once a month beside the standard regimen of verzenio fermara. I have Mets in chest wall and one single met in liver. Originally diagnosed in 2013 with stage 2A at the age of 36. Mets diagnosed in Jan 2019. 95 percent hormon positive.
JUST CURIOUS any one else in here is participating in this trial? This trial is available to UCLA HEALTH SYSTEM. My oncologist think this might be the next big revolutionary thing in metastatic BC.
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Chats, I hope the refill has you feeling better! Thinking about you and hoping you and your medical team get things figured out and get you on a treatment that is tolerable for you. I'm so envious of your retirement. Enjoy
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Welcome A,
I’m sorry about what brought you here....but here we all are! Wishing you all the best with your treatment. Please let us know more about the trial or if you have a web link, that would be great.
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Hi Ailurophile,
I think the trial you are talking about might be this one.
https://clinicaltrials.gov/ct2/show/NCT03099174
Certainly looks like they are very enthusiastic about Xentuzumab and the whole combo as they are extending it to multiple kinds of cancer.
Were you tested for something specific (mutations, etc.) before being enrolled?
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Daniel, that's an interesting study indeed. I think a multi-combination is one of the most likely paths to long-term control of MBC, at least until someone unlocks immunotherapy for us. This trial is blocking the IGF pathway with the Xentuzumab, in addition to ER and CDK4/6.
I'm bookmarking it to discuss with my oncologist as a potential option once Ibrance/letrozole stops working. This seems to be geared for second line therapy and would be one of the ways to keep getting a CDK inhibitor after progression on Ibrance. Hopefully they open more sites, because driving to New Haven from Boston once a week would be a pain.
I think Ailurophile said her "mystery" drug was a pill, so it's possibly this pi3K/mTOR trial for Lilly, which is open at UCLA. The only discrepancy is that the mystery pill is twice a day, not once a month.
https://clinicaltrials.gov/ct2/show/NCT01655225 part B7
Looks like an aggressive trial design trying to bring pi3K/mTOR drugs into the first line. I think they'd need pretty good tolerability (much better than everolimus) to be able to bring it to first line, but from a scientific perspective it does seem like a very attractive option. The single-agent results for LY3023414 in this trial showed a decent tolerability profile for 200mg/BID, which is the "recommended phase 2 dose (RP2D)". http://clincancerres.aacrjournals.org/content/24/1...
The B7 cohort seems to be an expansion, and is probably using this RP2D dose. We all know that doctors and patients don't always have the same understanding of "tolerable," so it will be interesting to see what people experience on the trial.
Ailurophile, I hope you are first of many to live years and years without progression on this treatment. We're all rooting for you and looking forward to learning about your experiences on the trial.
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Hi Dear friends, Thank you for welcoming me and replying to my post. I have 2 options:
option1 Fermara+ Palbociclib +Ivy 3 times in a month, no ivy in week 4.( it should be the ivy Daniel 86 is talking about)
Option2 Fermara+Abemaciclib (verzenio)+ mystery pill twice a day
My MO said these are practically the same, but since I have a young child, getting an ivy once a week is not something that I want to sign myself in for.
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Interesting discussion here, thanks Ailuro, for bringing it up!!
The design here is that inhibiting the PI3K/mTOR pathway along with the estrogen and CDK4,6 pathways should give a longer, stronger response than hitting any two of the three would.
However, you have to suffer along with the side effects of the PI3K/mTOR inhibitors (mouth sores, blood sugar spikes etc) for the entirety of the time you are on the combo, which is presumably significantly tougher than taking Ibrance-Femara.
I am not so sure about this being a better design, either. The reason is that primary tumors most often do not have activating PI3K mutations. They tend to pop up when the cancer mutates to escape from Femara (or Faslodex). Wouldn't it be better to start out with the cancer having the PI3K-mutation, in order to get the best response from the drug? That is what the trial with Alpelisib showed, for example, there was a clear benefit for those with PI3K mutations, but no benefit of the drug for those without PI3K mutations. So what is the rationale for taking a PI3K/mTOR inhibitor pre-emptively?
However, perhaps this new Lily drug has fewer side effects and they are seeing durable long responses in the combo as compared to IF alone?!! If so, terrific, because the longer you go before the cancer mutates the better, every time we get progression its a risk it has turned more aggressive, so fewer progressions the better. Best of luck on this new trial, and please keep us updated!!
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Ailuro,
PS Alternatively, your doctor may be concerned that you might be already resistant to estrogen inhibitor, or headed in that direction- although your cancer has high ER levels, if the mets were discovered while you were still taking an aromatase inhibitor, then they for sure would pick a trial like this, would be perfect for you..
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