AI induced bone and joint pain more common that reflected in clinical trials

[Lani]

Clin Breast Cancer. 2007 Oct;7(10):775-8. Links
Aromatase inhibitor-associated arthralgia and/ or bone pain: frequency and characterization in non-clinical trial patients.

Presant CA, Bosserman L, Young T, Vakil M, Horns R, Upadhyaya G, Ebrahimi B, Yeon C, Howard F.
Wilshire Oncology Medical Group, West Covina, CA 91790, USA. cary.presant@womgi.com
BACKGROUND: The frequency of aromatase inhibitor (AI)-associated arthralgia and/or bone pain in clinical practice is not known. PATIENTS AND METHODS: Fifty-six consecutive patients with breast cancer not on clinical trials who were receiving AIs in a clinical practice were interviewed regarding occurrence of worsening or new arthralgia and/or bone pain after starting AI therapy. The occurrence, character, severity, and resolution of pain were evaluated. RESULTS: Arthralgia and/or bone pain was reported in 61% of patients. It was severe in 30%, continuous in 41%, central in 50%, peripheral in 79%, and resulted in discontinuation of the drug in 20% of patients. Effective therapies in controlling pain were acetaminophen, 29%; nonsteroidal anti-inflammatory drugs, 50%; opiates, 18%, and glucosamine in 15% of patients. Despite this, 20% of patients discontinued AI therapy because of pain. CONCLUSION: Aromatase inhibitor-associated pain is more frequent in patients not in clinical trials than previously appreciated in clinical trials. Improved patient education is needed, and prompt therapeutic management of pain is required to ensure continued drug treatment and improved quality of life.
PMID: 18021478 [PubMed - indexed for MEDLINE]

[TSund]

Are the side affects of the AA's due to estrogen depletion or the chemicals of the drugs themselves?

ANyone know?

ALso interested in supplements or other that have helped as Ruth will probably be switched to an AA at some point in the future.

I see glucosamine referred to in this study. What else besides tylenol (hard on the liver) and anti-inflammatories (hard on the gut) might help?

Thanks

TRS

[MJo]

Sometimes I wonder about these clinical trials. I know they are necessary and I am extremely grateful, etc. etc. But doctors have to keep an open mind about what patients are telling them about the side effects of medicine, no matter what the clinical trials show.

[Lani]

and as the patients often could not obtain the drugs without participating in the trial perhaps the physicians feel pressured (consciously or unconsciously) to pay attention to the benefits and perhaps not so much to the complaints about the drugs--Hosting/participating in clinical trials ensures their patients' bills will be paid for and helps assure the drugs will become available for those not on the trial (even those who might want it off-label for another condition or indication later)--The overall effect seems to benefit patients as well as drug companies and the clinics/doctors sponsoring the trials, it seems

[TSund]

Lani,

Do you have any theories or knowledge on the "whys" of the side affects of the AA's?

[sassy]

AI induced bone and joint pain more common that reflected in clinical trials

Sorry, but DUH!

How many of us could have told them?

[Lani]

estrogen depletion in and of itself causes tendons and ligaments to tighten and become more elastic (why few 80 years can do the splits!)

Estrogen serves as a steroidal antiinflammatory in joints

Originally they thought that vitamin D levels which were low in bc patients might have something to do with it, but I don't think that has panned out, although it is still being looked into

Supplementing vitamin D didn't have the beneficial effect on this they had hoped for I was told by one researcher at a conference

I read today that statins can cause tendon deterioration and rupture, so perhaps RB can chime in with his views/information on the value of omega3s and 6s on this issue as it is possible that fat metabolism is involved

Hope this helped

[harrie]

I bet exercise helps reduce the tendon and joint pain. It would have been interesting to see those effects in the clinical trials.

[TSund]

THANK-YOU Lani!

As long as I have your attention, could you address this question of tamoxifen "UN-metabolizers" (sorry for the poor English) Do these studies that keep showing AI's with an advantage over tamoxifen take that percentage of women into account?

Ruth will probably switch anyhow to mute the possibility of endrometrial problems, but I am very leery of the sometimes severe side effects of the AI's. Ruth is a CPA and if she has trouble in her hands at the computer it would affect her job, and thus ultimately her health insurance.



THanks

Terri

[PinkGirl]

Yes Sassy, that's a big DUH!
They could have saved a lot of
time and money and just "lurked" on this site.

[Lani]

people (or that the testing method is accurate enough when done in most labs)
to really know how many have a different/better/worse metabolism of tamoxifen

Supposedly if tamoxifen takers get hot flashes that is a good sign that it is working(paper given at 2006 SAN ANTONIO MEETING I BELIEVE),but if one doesn't get hot flashes that doesn't necessarily mean it isn't working

Everyone's favorite mouse "triple cure" experiment by the Osborne/Schiff/Arpino team used estrogen deprivation as I recall rather than tamoxifen--I recommend you watch Dr. Osbornes talk videos from the Miami bc conference that I posted the link to a couple of weeks ago to check out his reasoning regarding different antihormonals for her2+s

Dr. Slamon has stated at meetings that he thinks faslodex may be best for her2s, but it doesn't seem to be available for those who haven't failed on either tamoxifen or AIs

If you use the search function you may find lots of abstracts, links I have posted on the relative merits of different antihormonals in her2+ breast cancer

[TSund]

Thanks Lani! Yes, I've looked at the video, and looked at some of the studies as well. When we spoke with our oncologist she ran the blood test that checked for this factor. As I understand it, a significant % of women (I was remembering about 5%, the article below says 7 -10%!) are poor metabolizers of tamoxifen, due to a certain gene/enzyme combination.


http://talk.dnadirect.com/2006/10/14...fen-2d6-genes/

If the drug company studies are not testing the women for this factor or taking into account the % of women that are poor metabolizers, then it seems to me that the statistics comparing the two are flawed. Don't get me wrong, I am not promoting one drug over the other and I have discomfort with both, but am just trying to get this straight. Has this factor been discussed elsewhere here on the board (or off!)

[Lani]

Cancer. 2008 Feb 1;112(3 Suppl):695-9.
Pharmacogenomics of tamoxifen and aromatase inhibitors.

Ingle JN.
Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota 55905, USA. ingle.james@mayo.edu
In selection of therapy for women with breast cancer, the focus has been almost exclusively on the characteristics of the tumor, eg, estrogen receptor (ER) and HER-2. Until recently, essentially no attention has been paid to the host and her genetic makeup as it relates to the metabolism of different drugs. The first real clinical application of pharmacogenetics in breast cancer management relates to tamoxifen's biotransformation to active anticancer metabolites. New information has arisen on the metabolism of tamoxifen to the active metabolite, 4 hydroxy-N-desmethyl-tamoxifen (endoxifen). Endoxifen is a metabolite with antitumor activity and affinity for the ER that is similar to 4-hydroxy-tamoxifen, but 1 that is normally present in substantially higher concentrations. CYP2D6 plays a central role in the metabolism to endoxifen and 1 published study shows that genotypic differences in CYP2D6 and use of CYP2D6 inhibitors has an impact on outcomes of women treated with tamoxifen. The aromatase inhibitors represent a major class of drugs in the armamentarium against breast cancer. The aromatase gene has been resequenced and functional genomics have been performed on the identified nonsynonymous coding single nucleotide polymorphisms showing significant decreases in levels of activity. These findings are consistent with a hypothesis that genetic variation in the CYP19 gene might be important in the activity of aromatase inhibitors. Currently, the emphasis is on examining multiple genes (thus pharmacogenomics) in pharmacodynamic and pharmacokinetic pathways in women receiving aromatase inhibitors for breast cancer. Cancer 2008. (c) 2007 American Cancer Society.
PMID: 18072234 [PubMed - in proce

[TSund]

So the AI's might ALSO have a class of women that don't metabolize them well...

I wonder if there is a test available for the DYP19 gene or enzyme also...

TRS

[Donna]

Hi Lani,

Thanks so much for posting this - I think the problems I am having with my hands is a combination of the tendon thing and mild lymphedema on the right side. The more information I have on this the better. I work with my hands and this is extremely troubling. What I wonder is this: will working with my hands in this condition damage my tendons permanently and is there anyone out there that can answer that question definitively???? Sometimes my fingers lock closed and my thumbs slip out of joint every time I move them. Bummer.

Have a great day, and Lani, please don't even think about this current trend for taking a break from the boards like so many are doing!

Donna

[harrie]

Donna, I am also concerned with problems with use of my hands since i am a dental hygienist. It is only my thumb that locks up and I can live with that. Sometimes i think that exercising your hands helps to prevent further problems. The reason I say that is because the prob is worst at night when I am sleeping and not using the hands at all. With my gym workouts and yoga, I think I might be preventing further joint problems. Not sure of course, but my guess.
Harrie