Anyone trying lower dosage for AI due to side effects?

[CLTann]

Under the separate thread of Arimidex or Femara side effects, it has been well concluded that about 40% of patients complained about bone and joint aches. Do those of you with side effects ever consulted with you oncs to see whether a half dosage of AI is the answer. I would be very much interested in going this route if there are indeed precedents to this approach. Please report.

[Debra]

Ann -

I just wanted to provide some input. I am 42 had been on arimidex for less then a year and really struggled with the joint pain. I was switched to aromasin and it made a HUGE difference. Other then my feet causing me some problems, although they always have, I am about 95% better. I also started exercising so I am not sure if it is 100% the aromasin or the exercise but I will say, I am a new person and life is so much better! I don't see aromasin mentioned a whole lot here on the sight but my oncologist felt there was absolutely no reason to suffer if there was other options that alleviated the pain and even indicated studies have shown it to be superior over some of the other AI's. Just my two cents!

[sadie]

I am glad to hear that it's not just me that is experiencing the joint pain (legs & feet).
I attribute it to weight gain and the arimidex (1mg daily).
I am continuing the arimidex because I am afraid to change from something that seems to be working for me.
I'm hoping that exercise will help the situation. I feel like my body is that of an 80 year old.

[Hopeful]

I reviewed the dosing and metabolism information from the websites of both Arimidex and Fermara prior to my fall onc visit, to see if I could go on a reduced dosage. According to the information I read, the standard dose is higher than the average patient requires to attain the degree of aromatase suppression the drug is designed to deliver. Arimidex does not provide for reduced dosing, even in patients with poor liver function, but Femara does. The reduced dosage is administered by taking a pill every other day, rather than every day. My onc said he has only done the lower dose regimen with very elderly patients whom he believed would have less aggressive disease. His opinion was that the half dosage did not work as well. This is another area I believe requires more immediate attention and study.

Hopeful

[TSund]

Hopeful,

I am very interested in this QOL issue. Does your onc base this opinion on any clinical evidence?

TRS

[Hopeful]

Terri,

None that I am aware of, though, truthfully, I don't think there is any. I think the Phase I trials of the drugs were done to test toxicity (i.e., what is the maximum dose you can take without it killing you) vs. what is the minimum amount you need to take for it to be effective. In private correspondence with a friend who works in the medical field, I was advised that the doses of the meds are likely set at levels that enable the fastest metabolizers to maintain the steady-state level of the drug in the blood that is the recommended dosage. What this means is that normal or slow metabolizers are having more of the drug floating around in their body than is probably required to do the job. I brought this up with my onc, and he said 1) he wished I had asked him the question a month earlier, as the "inventor of Femara" was a guest speaker at his practice's lunchtime CME and he could have gotten a good answer for me, and 2) it is his belief that circulating hormone levels do not remain level, even on these drugs, and go up and down somewhat. The latter is something I had never heard, and I am not sure why he thinks this; however, it was part of his rationale for not halving the dose. Perhaps the "Femara expert" discussed it in the CME.

Hopeful

[TSund]

This is good info Hopeful.

Re: circulating hormone levels; it actually makes some sense as women naturally have fluctuating levels. I read something recently that indicated estrogen is not completely controlled by ER moderating drugs including AI's and thus stressed the importance of exercize and weight control, both of which help control estrogen levels in the body. Brings in an irony; as if the AI's side affects are too extreme it could prevent the woman from getting regular exercize. (and that in turn could contribute to weight imbalance). Several here have said that exercize helped their symptoms, so I guess that's a win/win for them.

[Hopeful]

I just wanted to post this link from a 2003 interview with Dr. Paul Goss from Breast Cancer Update: http://www.breastcancerupdate.com/bcu2003/5/goss1.htm

as I think it has some information that comes to bear on some of the questions raised in this thread. I found his closing comments particularly interesting:

"I am very interested in how closely a woman’s health is related to a small range of estrogen. The slope of the postmenopausal estrogen range is a very small curve and is tightly related to breast cancer risk, osteoporosis and probably cardiovascular risk.

My personal feeling is that healthy postmenopausal women without breast cancer need their estrogen level “customized.” We can tone it up with HRT, but now we have a subtle way of toning it down. We have tried the two extremes — blockbuster ablation or massive replacement — but we haven’t tried zoning in on a middle range. I’m 100 percent convinced that in the next 10 to 15 years we will develop an understanding of women’s estrogen levels and their impact on health."

Hopeful

[miss di]

I have been asking about this since first go round. Always wondering why I have to take as much as someone with ovaries? (I had mine removed in 2000) obviously I would have less estrogen. When I asked, reply is always, but you still have "some". It also is stored in body fat, at this point I have no body fat and still have to take same amount, 1mg Arimidex daily.
Also, my second cancer is "mildly" estrogen positive, first time was "highly".
Would love an answer.
My best to all,
Di

[Donna]

Hi Amazing Group,

What I am wondering is this: I was already post menopausal and had none of these side effects. Is there something else in these medications doing the damage to the joints? I don't hear menopausal women complaining of trigger finger. This seems to uniformly hit our tendons, thumb first - should we as a group go to the manufacturers and demand answers?

I am thinking of visiting a remarkable hand specialist I know to see if he can shed some light on this.

Hoping we figure this out! Happy Easter to all!

Donna

[Becky]

Menopausal women still have some estrogen. The adrenal glands make it and fat cells make it. It is made using androgens that get converted via a (bio)chemical reaction to estrogen. The reaction needs an enzyme to make it go and that enzyme is aromotase. An aromatase inhibitor binds to aromatase and makes it unable to function as an enzyme in this reaction. Therefore you make less or in many cases no estrogen. Women with functioning ovaries (premenopausal) cannot take an AI because the ovaries produce estrogen in a different way so an AI would still block the way it is made from the adrenal and fat but that is such a small amount versus the ovarian mechanism - and a premenopausal woman would have no benefit as there would be tons of estrogen around.

Therefore, there can be a big difference in a menopausal woman versus a menopausal woman on an AI especially a menopausal woman who is also overweight (as they would be producing more estrogen).

No or very little estrogen is what is causing the symptoms - not necessarily the AI itself.

[Hopeful]

Becky,

Question for you. I have read a few places that the "next generation" of AI's will be ones that target only aromatase in breast tissue. My question is, when bc develops, even if some of the cells move out of the breast and into the body, they are still breast cells, right? So that an AI that targeted breast tissue would be able to exert its effect on all ER+ bc cells, wherever they may roam?

Hopeful

[TSund]

Re: Becky's post

Apparantly it is even more serious than that, I think there is speculation that the AI's can "turn on" the ovaries to produce extra estrogen when pre-menopausal. Like adding fuel to the fire.

TRS

[Becky]

Hopeful

I wonder how that would work. For example, you might stop the estrogen reaction in the breast but what about the rest of the body where estrogen would enter the blood stream and make it to the breast cells anyway - and the rest of the body, who knows? I really can't comment now but didn't want you to think I didn't read your question.

Terri - it is true that Femara is used to help induce multiple ovulations during invitro fertization procedures (at least in the UK it is).

[Joanne S]

http://smileys.smileycentral.com/cat/36/36_2_60.gif (http://www.smileycentral.com/?partner=ZSzeb001_ZNxmk788MNUS) My oncologist just recently switched me from Tamoxifen to Arimidex. I haven't noticed any difference in bone/joint pain as I've only been on Arimidex for 7 days, but the hot flashes with sweat pouring off my head and face is just overwhelmingly horrible. I imagine being overweight makes makes these symptons worse. Will these private summers improve? I too was wondering about the possibility of a lower or half dose of Arimidex.

My doctor explained that Arimidex blocks the production of estrogen where as Tamoxifen blocks the effects of estrogen.

Jo

[TSund]

Becky, have no idea of that one, but it sure is interesting if so. I was theorizing that working ovaries "sense" the lowering of estrogen in the body from the AI's and thus work harder to make more.

TO all following this conversation; do you have any opinions on DIM supplements? I didn't realize these may work specifically on the estrogen factor until reading a bit more lately.

TRS

[harrie]

Becky,
If the lack of estrogen is what is causing the symptoms of joint pain, I wonder why it is that some some AIs such as Aromasin or Femera cause some women less joint pain then Arimadex?

maryanne

[Melinda]

I just recently started taking Aromastin. For those of you that have been on ANY these AI's how long did it take before you became aware of the side effects such as trigger finger and joint pain. Any other side effects noticed?

[Donna]

Dear Becky,

Thanks so much for once again for your time and trouble to answer my question in terms I can understand. Your responses are always clear and illuminating. Your participation on this board is invaluable and I just want to say THANK YOU! HAVE A GREAT DAY!

Donna

P.S. just a "I wonder if" thought, would overweight women have a greater propensity to this tendon anomaly? I am overweight and I wonder just how hard those poor AI's have to work.....:-)

[KRISS]

I was only on tamoxafine for about 3 months when they switched me to femara after my hysterectomy. I had no side affects for the first 2 months but for the last three have had horrible joint and bone pain, not to mention the swelling in my hands. Some days I have no feelinging in either hand or only partial fingers. My knees hurt the most and with my physical job I'm in trouble. My Onc wants me to stay on it for at least 9 months to see if it lessens and then he might switch me. He believes there is no validity to switch. So we will wait it out a little longer.

[harrie]

It took me a few months to feel any joint side effects. I woke up in th middle of the night one night and my thumb was locked and I had to manually unlock it. I thought....."wow, that was REALLY wierd"....I had no idea it was from the Arimadex. During the day it was like nothing happened, then at night when I woke up, sure enough same thing.
harriecanarie

[lainy]

Here's a new dilemma...from a Newbie

Apropo of AI discussion: I am post-meno, a Senior, and have 2 diseases: OVCA Stage 111C, Grade 3 very aggressive. Separate Estrogen Receptor Test scored very high at 87%... very bad for OVCA. Responded very well to Firstline TAxol/Carbo, was also briefly put on Femara by GYN ONC to control , but Medical ONC disagreed, too risky (this was in 2005) and we used Evista which also is anti- estrogen and good for bone density. Post- Surgery, with optimal debulking, even before chemo, I went into remission since FEb. 2005.

Here is my dilemma, was dx'd and had surgery for left breast cancer last year in June 2007, a Lumpectomy: Stage 1, invasive ductal carcinoma, tumor 0.9, no lymph node involvement, (think, margins clear...am drowning in paper lately, can't find Pathology report at the moment) but remember all the other specs which are "lousy"!! Grade 2, Her2 high positve, BUT, contrary to most of you that I've read about thus far... I am estrogen and progesterone NEGATIVE...the exact opposite of my OVCA... not only bad news for breast CA, also a conflict in terms of choice of adjuvant therapy. Am painfully aware that what would help my breast cancer could harm my Ovarian remission. Know that my Grade 2 NEGATIVE's, combined with a High HER2 positive puts me at greater risk for tumor growh and recurrence. Thus far I've had 6 weeks of Radiation, (plus a breast infection), followed by Herceptin, every 3 weeks which I'm tolerating very well with one exception...my Muga score was good but right ventricle may be under-expressing. Have Cardio appointment on Monday to check. Also, ONC uses the 2729 tumor test and my numbers have slowly gone up, slightly past the normal cut-off point. He's not concerned yet.

Am still using Evista, but need to find out more about newer chemos, ( found out latethat I could be a candidate for chemo, either systemic of IV along with the Herceptin...( I'm at the halfway point of one year of treatment.) Is there anyone with Negative Estrogen specs similar to mine who has looked into Tykerb, Xeloda or anything else that might be compatible with my 87% Positive OVCA ER test reults.?

Im still learning how to navigate this website...so thankful to have found it. Looking forward to participating.

[TSund]

Kriss,

I think it absurd that he won't try switching you. It doesn't seem like it would hurt trying. Some of these docs have certain pharmaceutical "allegiances".

If you are in that much pain, it doesn't make any sense not to try. I'd be insistent!!

TRS

[TSund]

Lainy,

I didn't know that anti-hormonal treatment is bad for non-ER+ bc. I know it doesn't HELP the bc, but I am not so sure it is a "negative". (?)

Also, a chemo like TCH could be effective for your bc and also effective on the other, as it would likely throw you into "chemopause".

Wishing you the best,

TRS