Taxotere, Carboplatin and Herceptin
Comments
-
It is either fluid retention for me or weight gain?
I weigh more now than I ever did before chemo. This includes right after having had twins.
My socks and shoes are tight so I am trying to figure out if I need more exercise or what.
0 -
Hi all, I haven't posted on this site for a long time, but came across this study and found it interesting and it applies to many of us who had TCH. I don't like it very much. . .
Health News 
Videos Article Opinions Forum Advertise Contact 
Follow us on:
News Archive [link] Web Wikipedia Medical Dictionary [link] 
Personalization
login | registerBreast Cancer News Useful Links Video Library 
Erythropoietin Counteracts Breast Cancer Treatment With Herceptin
Retweet Main Category: Breast Cancer
Also Included In: Biology / Biochemistry
Article Date: 16 Nov 2010 - 2:00 PST
email to a friend 
printer friendly 
opinions
Current Article Ratings:
Red-blood-cell-boosting drugs used to treat anemia may undermine breast cancer treatment with Herceptin, a targeted therapy that blocks the cancer-promoting HER2 protein, researchers from The University of Texas MD Anderson Cancer Center report in the Nov. 16 edition of Cancer Cell.Patient / Public: 
Healthcare Prof: Article Opinions: 0 posts
"Our research indicates when the two drugs were used at the same time, Herceptin was less effective," said study senior author Zhen Fan, M.D., associate professor in MD Anderson's Department of Experimental Therapeutics.
Natural erythropoietin (EPO) controls the body's red blood cell production. Manufactured versions called erythropoietin-stimulating agents or recombinant erythropoietin treat anemia caused by kidney failure and cancer treatment.
"Recombinant erythropoietin is a great drug, and it's saved many lives," Fan said. "Some studies, however, have shown that the drug has effects on cancer cells. We wanted to see if recombinant erythropoietin thwarts Herceptin, based on our understanding of how the two drugs work."
The researchers tested their hypothesis using breast cancer mouse models, then followed up with laboratory experiments on cancer cell lines to work out the molecular details. A retrospective case control study of 111 breast cancer patients supported their findings from the mouse studies.
Human epidermal growth factor receptor-2 (HER2) is overexpressed in 25-30 percent of breast cancers. The drug trastuzumab, known commercially as Herceptin, is an antibody designed to block HER2. Because resistance develops, only about a third of HER2-positive patients respond to the drug.
The presence of functional erythropoietin receptors on HER2-positive breast cancer could be one resistance mechanism, Fan said.
"The whole idea with targeted therapy against the HER2 protein is to shut off the downstream molecular activity launched by HER2," Fan said.
"Erythropoietin can activate similar downstream pathways if its receptor is expressed on cancer cells, causing antagonism between the two drugs."
Fan and colleagues demonstrate that when erythropoietin connects with its receptor protein (EpoR), it launches a chain of events that activates Src, a crucial component of a pathway that trastuzumab blocks. It also shuts down a well-known tumor-suppressing gene called PTEN that is believed to be important to trastuzumab's activity against cancer cells.
There is controversy in academic circles about the role and function of EpoR in cancer cells and other types of cells not involved in blood production. It's important to note, Fan said, the team found no evidence that recombinant erythropoietin alone promotes cancer growth.
Tracking down the details
In three HER2-positive breast cancer cell lines, trastuzumab inhibited cell survival and proliferation, while recombinant erythropoietin stimulated cell survival and growth. When the three lines were treated together with trastuzumab and the anemia drug, cell survival increased from 58 percent to 80 percent, 57 percent to 77 percent, and 34 percent to 57.5 percent, respectively.
Two HER2-positive breast cancer cell types were introduced to mice, who then either received mock treatment, trastuzumab only, erythropoietin only or both drugs. Tumors treated with trastuzumab either shrank or stopped growing, with average tumor volume close to zero after 50 days in one cell line and barely registering in another. Growth of tumors treated with erythropoietin closely tracked the control group, increasing rapidly to an average volume of 1,500 cubic millimeters in one line and 600 mm3 in another. Tumors treated with both drugs grew more slowly to about 700 mm3 and 300 mm3.
Improved patient survival in small study
In a retrospective case-control study of patients with HER2-positive breast cancer that had spread, the team compared overall survival and progression-free survival between a group of 37 patients who received trastuzumab plus chemotherapy and recombinant erythropoietin to a matched control group of 74 whose cancer was treated the same way but who received no EPO.
A statistically significant difference in progression-free survival emerged at one year, with 40 percent of the control group having stable disease compared with 19 percent of the erythropoietin group. Overall progression-free survival differences across two years were not statistically significant.
The control group also had better overall survival than the erythropoietin group that was statistically significant in an analysis of multiple variables.
Fan emphasized that clinical findings should be interpreted with caution because the study was small and retrospective. Patients who received erythropoietin might have been sicker than the patients not treated with erythropoietin. Their findings need to be confirmed by larger clinical studies.
"We're expanding this study to include other types of cancer," Fan said. "Of course, different types of cancers are treated with different types of targeted therapies. We need to design our studies using different targeting agents than Herceptin to study whether erythropoietin can antagonize these drugs," Fan said.
Looking forward, Fan said, researchers need to find out why and how some cancer cells express the receptor protein for erythropoietin, and to what extent cancer cells express EpoR. "Recombinant erythropoietin helps to improve a patient's general condition without the need for a blood transfusion," Fan said. "If we can figure out how the expression of the erythropoietin receptor is regulated in cancer cells, we may come up with some new strategies to allow cancer patients to receive the drug for their anemia and fatigue without compromising their treatment with novel targeted therapies, such as anti-HER2 therapy with Herceptin."
The study was funded by a grant from the National Cancer Institute, research awards by the Breast Cancer Research Foundation, and by MD Anderson's Cancer Center Support Grant from from the NCI.
Co-authors with Fan, all from MD Anderson, are first author Ke Liang, Yang Lu, Xinqun Li, M.D., Ph.D., and John Mendelsohn, M.D., all of the department of Experimental Therapeutics; Francisco Esteva, M.D., Ph.D., Giampaolo Bianchini, M.D., Ching-Yi Yang and Gabriel Hortobagyi, M.D., all of the Department of Breast Medical Oncology; Yong Li, Ph.D., Constance Albarracin, M.D., Ph.D., of the Department of Pathology; Katherine Stemke-Hale, Ph.D., and Gordon Mills, M.D., Ph.D., of the Department of Systems Biology; and Chun-Te Chen and Mien-Chie Hung, M.D., Ph.D., of the Department of Molecular and Cellular Oncology.
Source: University of Texas M. D. Anderson Cancer Center
0 -
Oh gee, I don't know how to get rid of all the goobly gop on the top, but the main article is there underneath it all. Sorry.
0 -
weety - thanks for the article. I am glad I didn't get EPO but I did get neulasta which is somewhat different I think since it is granulocyte colony-stimulating factor (GCSF). However, I did find this info which is very similar to the EPO info:
The granulocyte colony-stimulating factor (G-CSF) receptor, through which pegfilgrastim and filgrastim act, has been found on tumor cell lines. The possibility that pegfilgrastim acts as a growth factor for any tumor type, including myeloid malignancies and myelodysplasia, diseases for which pegfilgrastim is not approved, cannot be excluded.
At this site: http://www.neulastahcp.com/
0 -
weety - thanks for the post, my wife had her second TCH today, at Tuesday's blood test they told her she was slightly anemic and prescribed an OTC iron supplement. I'll keep this handy if they want to follow-up with a red blood cell booster.
0 -
just got back from number four chemo, couldnt find a great vein, so i will have to get a port, one of the techs said my arm looked like a drug users arm. It looks bad but it will heal now to get the port, which i feel might be for the chemo nurses advantage. its easier for them. hope for subtle s/e
0 -
Thanks weety Very interesting. I so far haven't had issues with my red counts (just had tx #5) so I'm not too concerned. I do take nuelasta but that's for the white count and a different drug. Hopefully I won't need to worry about my red counts.
Starella, you will love the port.
0 -
Hi All,
This website has some useful information about edema (water retention):
http://www.annecollins.com/weight_health/water-retention-fluid-edema.htm
I cana tell I've got water weight gain when I do the pitting test: I press my thumb into my thick ankle, foot, forearm, or wherever and hold the thumb press for 10 seconds or so and the pit or indentation in my skin remains for far longer than would be normal. It's like I'm pressing into play dough. Very gross (or sometimes I can find the humor in this when I chaulk it up as a "stupid human trick"). But, it does tell me the weight I'm carrying is from fluid retention. Still unpleasant!
in the last 24 hours, I've gained back about 3 pounds of the weight/fluid I had lost in the last week or two. And the only change I can attribute this to is my going off diuretics. I didn't think they were working. Now, I think they probably were. I'm hoping the oncologist re-news my prescription and I can test this theory out. The only question I have is how long it's safe to stay on diuretics. (It stuns me that I'm still having significant side effects from the taxotere even though I'm 5.5 weeks post chemo. It's a reminder how strong chemo is -- what damage it does to cancer cells AND other cells.)
Best wishes to all,
Katherine
0 -
Katherine~
I finished my taxotere in March and unfortunately I am still having water retention and achy joints. My oncologist said to give it a full year and see if it is getting better...
0 -
I did have the procrit shots, but only a couple of them. I held off as long as I could. My onc kept pushing them, so finally near the end of my chemo, I did about 2 weeks with the shots. I hope that wasn't enough to counteract the treatment.
0 -
weety - There are so many things about all this that we don't understand and the medical field doesn't understand either. I think we just have to do the best we can. I stoped chemo at 5 out of the 6 TCH's (still going with H thank goodness). It bugs me but because of the nerve issues it seemed like the right choice. Best I could do.0
-
I finished TC at the end of May; I didn't have much of a problem with water retention, but I have had a lot of achy joints. I'm still on Herceptin/Avastin (only one left!). The aches are getting better, and my energy is good. I like to think I have no Herceptin reactions, although I have noticed being really tired after the last few treatments, but that just lasts a day. Mostly my energy is normal, I'm exercising well, and I've been able to not regain the weight I lost, even with the Tamoxifen.
0 -
Writer,
That is awesome about not gaining on Tamox...I read such horror stories...thanks!!
0 -
Yeah, I was really worried about it, but it hasn't been an issue. And I'm not starving myself. And I've been on the overweight side most of my life. I lost weight before getting diagnosed (in response to distressing photos of me around my 50th birthday), and then lost some more from cancer stress and chemo. I had heard so many bad things about Tamoxifen, but my oncologist insists that it's not that much of a side effect-- that usually the weight gain is from menopausal middle age, and women would have it anyway. He said if I kept up the exercise, it would be fine, and so far he's right. And I don't exercise as intensely as you... just walking and pilates and maybe one good gym sweat a week.
0 -
WOO HOO!!
I love good news!
Thanks writer.
0 -
"The drug trastuzumab, known commercially as Herceptin, is an antibody designed to block HER2. Because resistance develops, only about a third of HER2-positive patients respond to the drug."
quoted from the article above. WHAT? One of my greatest SEs is chemo brain. Only 1/3 of us will respond to Herceptin? I'm chemo-confused. Anyone got clarity -- I will try and track down.
0 -
Well, I don't know the real answer, but I'm thinking that means HER2+ metastatic cancer in which the women have been on the herceptin indefinately and thus the resistance eventually shows up???
0 -
Weety I have read the same thing. For the rest of us I hear it's more like 50% benefit from Hereceptin.
0 -
tara - I looked at the Cancer Cell original article on Epo and HER2 and it is very complex. It looks to me like the results quoted apply to cancer cells that express both HER2 and the Epo receptor which not all HER2 positive cells do and second the comment about the 1/3 non-responders was not in the original ariticle but in the summary article only so I don't know what the reference for that is. Perhaps the summary author was just saying that without a real reference???0
-
Thanks everyone for helping with clarity. I finished my 6 TCH last week, still waiting for that boost of juicy energy ... hopefully tomorrow - and I'm still so upset with my ONC and reading this sent me over the edge. She'd just pat me on the head and say don't worry. I don't want to take Tamoxifen, and even showed her some studies that say it doesn't help with HER2+ gals. So then she says it will still help me with my joints and lipid levels. What has that got to do with breast cancer? And if I'm taking much better care of myself with diet/exercise ... who needs to plop on more drugs?
I still have 12 herceptins to go through August. What tactic do I now take to find a different ONC to do all my follow up care? I want someone to give me citations to studies, if not the studies themselves so I will be as educated as possible. Someone who will be able to say, here's what we know, and what we don't know, and you have to decide. I am going on Jan. 4 to a "survivorship clinic" at my hospital. I hope I will be able to be chemobrain free and advocate for what I need as a patient and survivor.
0 -
Tara not all HER2+ women don't respond to Tamoxifen. There are plenty that are on it. Here are a few links but I'm not sure how old the info is. I can't say I understand all that is being said either.
Does HER2 Overexpression Predict Adjuvant Tamoxifen Failure in Patients With Breast Cancer?
If you are menapausal or if their is a possibility that chemo put you in permanent chemo-pause then I would think ALs would be a better choice… but I'm no oncologist. I think you also need to know what benefit you would get from this versus risk of SE. I think the best thing you can do now is get a second opinion from another onc. Is there another hospital near you? I forget where you live.
You can search for doctors here but remember that not all the good doctors will be listed: http://www.castleconnolly.com/
US news top ranked hospitals for cancer in the US
http://health.usnews.com/best-hospitals/rankings/cancer?page=10 -
★ ✩ ★ ✩ ★ HAPPY NEW YEARS!!! ★ ✩ ★ ✩ ★
░░░░░▓███▓
★ ✩ ★ ✩ ★ ✩ ★ ✩ ★ ✩ ★ ✩ ★ ✩ ★
░░░░▓█████▓
░░░░▓█████▓
░░░░░▓███▓
░░░░ *;;;;;;;;;*
░░░░* ;;;;;;;;;;*
░░░ * ;;;;;;;;;;;;*
░░░* ;;;;;;;;;;;;;;*
░░░░▓█████▓
░░░░▓█████▓
░░░░▓█████▓
░░░▓███████▓
░░▓█████████▓
░▓███████████▓
▓█████████████▓
▓███░░░░░░░▀▀▀▓
▓███░░░░████████████
▓███░░░░█▒▒▒▒▒▒▒▒▒▒█
▓███░░░░░█▒▒▒▒▒▒▒▒█
▓███░░░░░░█▒▒▒▒▒▒█
▓███░░░░░░░█▒▒▒▒█
▓███░░░░░░░░████
▓███░░░░░░░░▌██▌
▓███░░░░░░░░▌██▌
▓███░░░░░░░░▌██▌
▓███░░░░░░░░▌██▌
░▓██░░░░░░░▓████▓
░░▓████▓▓████████▓
░░░░░░░░░░░░░░░░░░░░░
█████░█████░░███░░███
█░░██░██░██░████░████
░░░██░██░██░░░██░░░██
░░██░░██░██░░░██░░░██
░██░░░██░██░░░██░░░██
██░██░██░██░░░██░░░██
█████░█████░░░██░░░██0 -
Another question.
Is anyone having really bizarre dreams about 3 days after TCH?
And hot flashes. Goodness, last night I woke up at least 30 times from them....sweating, then freezing....I really don't want to take any meds for it since I am already a walking pharmacy. Any natural cures?
But the dreams. ... Felt like I was losing my mind.
0 -
I have the hot flashes. They can wake me up but then I go back to sleep. I do hear that certain foods like spicy or alcohol can make things worse.
The dream thing sounds like maybe the emend, zyrtec, clariton or some other drug that can make you drowsy might be messing with your mind.
0 -
Thanks Lago for this information. I'm stuck in Omaha Nebraska for care. Our hospitals aren't even ranked in the US News list. The U of Nebraska hospital doctors who work in the lymphoma/Hodgkins area are on the Castle Connelly list.
I showed my ONC the second article you linked Lago, and she said those were studies "too new". She wants me on Tamox for 2 years then AIs. She won't even test my pre-menopause phase. She forgets who I am half the time. I already visited the Cancer Treatment Cetners of America and boy was that a bad experience with the first lumpectomy.
Hmmmm. Perhaps Mayo Clinic in Rochester MN is the best place to go. I am going to a survivorship clinic Jan. 4 here, so I'll see how they deal with my resistance and questions, and I'll make some calls to the Mayo Clinic.
Happy New Year!!!
0 -
I am going to Mayo for my reconstruction I have my consultation there next Fri.
0 -
Happy New Year!!! DH and I stayed in and watched the movie Grown ups, it was funny. I made it through week 1 of rad. the only se I could feel at this point was tiredness, I feel ok today and no rad. on the wkend. No redness or irritation yet, RO said by the looks of my skin I may not get the redness.
I am supper excited to be taking a trip to Fl. the week after I am done with rads. It will do my body good to sit on the beach and soak up the beautiful surroundings. My best friend and her man are going with us, I can't wait!!
Hope you are all getting through your tx with little se, hugs and prayers to each.
0 -
Happy New Year Sue!0
-
Lizzy - How are you doing today?0
-
Too tired to make this new and exciting.....(har) posted on the Taxotere thread as well.
Yesterday I was weak and dizzy all day.
Last night was horrible.
I was constipated (didn't happen last time) even with Metamucil 2 xs a day. So, I took an Ex Lax, and 12 hours later, with no relief, but severe abdominal pain, an enema. That got things moving, but constipation turned to diarrhea and severe shivering.
Still, considering the "lack" of action down there in the last couple days....there wasn't a lot of production if you know what I mean.
I couldn't stop shivering, laid in front of the fire, and my temperature spiked. I didn't go to the ER, I took a Tylenol. I was too weak and tired to go to the ER. After two hours my temp settled down to around 99-100, shivering slowed, and I went to bed.
Today, I am sore everywhere from the constant muscle clenching....and now my youngest has diarrhea.
To top it all off, I think chemo gives me UTIs. Anyone else have this problem every time?? (I've never had one until now. And if one more person tells me to wipe front to back!! GRRR!! I'm 42 years old, I've managed to do that for 40 years, do they think chemo makes me stupid?)
My urine is darkening up again, just like last treatment when I got a UTI. And right now I can't tell if my back hurts from all the drama yesterday, or from the UTI.
I'm gonna try and wait until Tuesday when I go in for Herceptin ... depends on the fever thing.
I'm only 2 treatments in and right now I think the chemo is going to kill me. I don't know how I can do this every 3 weeks.....
0
