Need Your Advice Again

[IRENE FROM TAMPA]

My friends, once more I am asking for your advice/experiences.

As some of you know, I have been dealing with my cancer for the last 10 1/2 years with many recurrences in between. My options are running very low and here is where I am at moment.

After having my liver surgery in July/2004 I was stable for 8 months when I had a recurrence to a lymph node behind the pancreas, by the liver. I started on Abraxane (without Herceptin which I had been on since 1999) again I was stable until March of this year when a second tumor popped up next to the other one in a lymph node. I started on Taxol/Carboplatin/Herceptin in April - June of this year when my markers started to elevate. I was rescanned again and both of the tumors have almost doubled in size. We stopped the treatment and at present am on Herceptin only waiting to see what to do next. It seems that the trio did absolutely nothing to even stall the growth.

Here are my options now -

I can start taking Avastin (which I understand is extremely expensive)
or
I have found a trial which is open in Gainsville, Fl which has a Phase III being conducted.
It will be Tykerb alone or Tykerb with Herceptin.
I also found a trial which will be starting up at the office of my first onc.-
Their's will be Tykerb with Xeloda. They are in the process of getting all of their paperwork together which could take about 3 weeks or so. Of course, this office would be more convenient for me.
The office in Gainsville is already up and running. I would just need to make appt. with the doctor to be sure I qualify and everything would probably take about 2 weeks.

I believe that I pass all of the criteria which is required (which is tough according to the co-ordinator) and I have been off of chemo for 3 weeks already, which is required (Herceptin is ok to be on)I am afraid to start back on chemo and jeporadize my chances of starting on the trial but am also nervous about waiting for nearly another month without any chemo.

I don't know what to do - Then I think, would the Avastin work better? I could start on that right away. It's really a toss of the coin to see.

My question - is anyone on Avastin or Tykerb and how is every thing going.
In what I am reading about Avastin makes it sound promising but then everyone is so anxious to get on Tykerb. Here I may have the opportunity to do so and I don't know which way to go. The waiting time has me a bit nervous also.

Any input from anyone would really be helpful. Although I know that none of us are experts in the medical field, sometimes discussing our experiences helps in making a very difficult decison a little easier.

If anyone is interested in the names and addresses for the offices that will be conducting these trials in my area, please let me know and I will pass on the info. Like I mentioned one is in Tampa, Fl and the other is in Gainsville, Fl. for those of you on this side (or not).

The criteria list is long, but you have had to have been on at least 2 regimens of chemo plus Herceptin and have failed and have progression while on it to qualify. Scary thought huh.

Thank you all for all of your help and support.

[chrisy]

Hi Irene,
Sorry to hear you are having to make treatment decisions again so soon. You're such a fighter and an inspiration. Just wanted to respond to let you know I'll be thinking of you. I'm sorry I don't really have anything to offer in terms of experience with any of these options you are considering. I'd just say get as much information as you can (which you are doing now) then trust your heart.
Hugs
Chris

[Lolly]

Hi Irene;

I too am sorry to hear you're in that limbo land we all hate. Here's a link to an earlier thread where two have posted about their Tykerb trials...maybe you could send them each a private message asking for more detail? At any rate, I'm thinking about you and hoping you can reach a decision. I was interested in the Tykerb/Xeloda trial, and considered it but ended up dropping Navelbine and adding Xeloda to my Herceptin, but the Tykerb/Xeloda combo seemed like a very promising one to me. However, I have no experience to back up my hunch, except to say I've found Xeloda/Herceptin very tolerable. If I start to have progression again, I'm going to explore adding Tykerb.

<3 Lolly

[Shell]

Hello Irene-


I agree w/ the others - you are an inspiration. I don't know anything about Avastin, but I am on the xeloda w/ or without tykerb trial. I was getting the arm without tykerb, but in April we all started getting both. Tykerb seems to have very few side effects that you don't already get with xeloda. The major 2 issues with xeloda are H/F syndrome and diarrhea. Adding tykerb to the mix added fatigue for the 1st few days, and a little more frequent diarrhea.

Both drugs are in pill form,and thus I only visit the doctor once every 3 months (with blood draws every 3 weeks). I am stable now, but hope the scans in Aug w a bit more time on the tykerb will kick things back even further.

Good luck w things, and keep us posted!
Shell

[Becky]

Dear Irene


Although I am not in your position, Avastin is a drug that you can try anytime but a trial that gets you Tykerb, which is not on the market for any indication yet is an opportunity. If the Tykerb doesn't work, you can always try the Avastin then.

I will keep you in my thoughts and prayers.

Kind regards

Becky

[IRENE FROM TAMPA]

for your replies. I appreciate your comments so much. I don't know how much of an inspiration I have been (although I try) but I do know that I am a fighter and even though each time I get a recurrence it knocks me back a few feet, I do try to get back my balance and control over this as quickly as I can.

This might seem secondary, but we have had a trip to Italy planned for the last year and are now in limbo as to if we can still make it. Our trip is planned for August 23 thru Sept. 26. We are so looking forward to this trip that it is all I could dream about. Coming from an Italian background, we just want to mingle in with the people and relax and get all of this illness off of our minds. My poor husband has been through Hell himself being my caregiver, so this trip is kind of special to him too.

All this making my decison even harder, if I decide on the Tykerb/Xeloda trial- they are both pill forms so I could possibly travel with the drugs (if they show to be working and I don't show progression) If I choose the Tykerb/Herceptin trial I have to have the Herceptin weekly so may not be able to be away. If I choose the Avastin (which the concept of how it works sounds promising) that's an infusion also. I understand that Avastin has only been approved for colorectal cancer so am wondering if I can even get approved to take . The fustration is not knowing (and no one knows this) which one would work best without wasting any time since my tumors are growing. I am having tumor markers drawn next Tues. and see my onc. on Wed. and I will discuss further with her.

Like I said, the trip being as important as it is to us, is secondary to my life and I have access to a trial in my area, so I dont want to sound like I am whinning - I guess I am just "sharing" my fustrations of all of these years
with ladies who truly understand what it is like and for this I am truly so grateful to have all of you. I love you all....

thank you so much for your patience and for letting me rattle on.

[IRENE FROM TAMPA]

I failed to mention in my message above that it will take about 3 - 4 weeks to get into the Tykerb trials between seeing the doctors and paperwork. That is another reason I am concerned since I have already been off of chemo for three weeks.

This scares me so that is another reason why I was considering Avastin since that might be readily available to me by next week.

Just decisions to have to make by next week and pray I make a good choice.

Thanks again.

[StephN]

If taking the Avastin does no6t preclude you from the Tykerb trial, you may want to go for that.

I bet the Tykerb trials would still be open, but you can check on the "fill" rate and start the process.

After having a 3 week trip to Portugal in May, I can't tell you how much GOOD it did my husband. My poor darling has been helping me for 6 years now and does this willingly, plus still works. Not many men are like that - shops, cooks, cleans up. Really - the trip did us BOTH a lot of good. When you are away you are busy with the immediate sights and sounds around you and your daily agenda. ALso, it takes time and energy to understand things in another language. You have very little time to think about the cancer and this is worth A LOT.

The difference between us is that I left with a basically clean bill of health. If you can sort out a new treatment plan, try to take the trip or a shortened version if you have to.

All best wishes for your decision making.

[R.B.]

I am trying to tread with care as a male non sufferer who has just doen a bit of reading posting to some one who has spent so many years at the sharp end of this dreadful disease.

I flipped through the summaries of your posts and noted you take omega three supplements.

Did you have a chance to read the recent greek diet posts, and particularly the latter ones linking inflamation (COX 2 pathway based) and various cancers, including a post suggesting that fih oil infusions may reduce the inflamatory markers, and posts looking at positive results from cox blockers at low level plus DHA on cancer reduction.

From all I have read in respect of the three six debate I cannot emphasise enough the role of the omega six derivatives, and the potential importance of restricting omega six intake as well as taking three to try and at least balance the threes and sixes if you were looking at threes and sixes, inflamatory markers etc.

From what I have read digestive distrubances can exacerbate the bodies inability to sythesise long chain n3 fats which might be another argument for intravenous provision.

It is on the "edge" but you might like to show it to your onc. Could any of it be used as an adjunct to any other treatment chosen, with appropriate monitoring of inflamatory markers etc.? - one for the professionals to answer.

On another topic here is a link to the side effects of Avastin if you have not had time to find one?

http://www.rxlist.com/cgi/generic3/avastin_ad.htm

I am sure that you are well aware of the need to discuss dietary change with your medical advisors. My intention is to try and inform the debate on the work of others so that other others may advise.

Respectfully

RB

[R.B.]

There are many lacks in my knowledge so this is a bit of a guess from a half fhinished jigsaw but food for thought, and one for discussion with your onc.

Omega three has been shown to downregulate BC.

FAS part of the system the body uses to make fats is one of the pathways used by herceptin. (see below)

IF the body is dupplied with adequate levels of long chain DHA EPA etc fats in diet it stops making them, and so must be not using switching of FAS in some way. (lots of trials on NCBI)

The olive oil trial would suggest that the herceptin mechanisms are sensitive to fats intake. (see below)

Fish oils contain high levels 18:1 monsaturates (although it does not specify which) so the chances are that you may by taking fish oil (see analysys below);

1. Moderate fas pathways

2. Get the benifits ascribed to fish oil in BC

3. Cut down body inflamation

4. Get benifits from the 18:1s

5. Improve your nutrition

IT IS ESSENTIAL TO CUT RIGHT DOWN ON OMEGA SIX.

In terms of intravenous provision they use it for the very ill with benificial effects, but if your digestion is poor it might be a way of ensuring you are getting long chain threes into your system. Form the trial take up is better than from taking from diet.


I am only a dest top jockey so definately stuff for discussion with medical advisors.


Suggested optimal intake of DHA in a trail was two grams DHA a day which is about 5tps of a quality fish oil. I take double that plus at the moment. There are few reported side effects but blood thining is one and again you must consult with your advisors. DHA is a component of fish oil - check the label.

Trials suggest that the body's stored six can reduce the effect of intake of threes and hence my decision to take a higher level for a while.

Fish oil also help with irratable bowel etc., which is another inflamation based condition. (an interest of mine and it has improved significantly - balancing the threes and sixes is the biggest dietary change I have made)

Vitacost

http://www.vitacost.com/?csrc=SITEREF-linkshare

do a quality reasonably priced cod liver oil with no backtaste. Again I have no connection with the company except as a customer.


RB






http://www.nutritiondata.com/facts-B00001-01c20AC.html


http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_docsum

1: Ann Oncol. 2005 Mar;16(3):359-71. Epub 2005 Jan 10. Related Articles, Links
Click here to read
Comment in:

* Ann Oncol. 2005 Mar;16(3):339-40.


Oleic acid, the main monounsaturated fatty acid of olive oil, suppresses Her-2/neu (erbB-2) expression and synergistically enhances the growth inhibitory effects of trastuzumab (Herceptin) in breast cancer cells with Her-2/neu oncogene amplification.

Menendez JA, Vellon L, Colomer R, Lupu R.

Department of Medicine, Breast Cancer Translational Research Laboratory, Evanston Northwestern Healthcare Research Institute, 1001 University Place, Evanston, IL 60201, USA.

BACKGROUND: The relationship between the intake of olive oil, the richest dietary source of the monounsaturated fatty acid oleic acid (OA; 18:1n-9), and breast cancer risk and progression has become a controversial issue. Moreover, it has been suggested that the protective effects of olive oil against breast cancer may be due to some other components of the oil rather than to a direct effect of OA. METHODS: Using flow cytometry, western blotting, immunofluorescence microscopy, metabolic status (MTT), soft-agar colony formation, enzymatic in situ labeling of apoptosis-induced DNA double-strand breaks (TUNEL assay analyses), and caspase-3-dependent poly-ADP ribose polymerase (PARP) cleavage assays, we characterized the effects of exogenous supplementation with OA on the expression of Her-2/neu oncogene, which plays an active role in breast cancer etiology and progression. In addition, we investigated the effects of OA on the efficacy of trastuzumab (Herceptin), a humanized monoclonal antibody binding with high affinity to the ectodomain of the Her-2/neu-coded p185(Her-2/neu) oncoprotein. To study these issues we used BT-474 and SKBr-3 breast cancer cells, which naturally exhibit amplification of the Her-2/neu oncogene. RESULTS: Flow cytometric analyses demonstrated a dramatic (up to 46%) reduction of cell surface-associated p185(Her-2/neu) following treatment of the Her-2/neu-overexpressors BT-474 and SK-Br3 with OA. Indeed, this effect was comparable to that found following exposure to optimal concentrations of trastuzumab (up to 48% reduction with 20 microg/ml trastuzumab). Remarkably, the concurrent exposure to OA and suboptimal concentrations of trastuzumab (5 microg/ml) synergistically down-regulated Her-2/neu expression, as determined by flow cytometry (up to 70% reduction), immunoblotting, and immunofluorescence microscopy studies. The nature of the cytotoxic interaction between OA and trastuzumab revealed a strong synergism, as assessed by MTT-based cell viability and anchorage-independent soft-agar colony formation assays. Moreover, OA co-exposure synergistically enhanced trastuzumab efficacy towards Her-2/neu overexpressors by promoting DNA fragmentation associated with apoptotic cell death, as confirmed by TUNEL and caspase-3-dependent PARP cleavage. In addition, treatment with OA and trastuzumab dramatically increased both the expression and the nuclear accumulation of p27(Kip1), a cyclin-dependent kinase inhibitor playing a key role in the onset and progression of Her-2/neu-related breast cancer. Finally, OA co-exposure significantly enhanced the ability of trastuzumab to inhibit signaling pathways downstream of Her-2/neu, including phosphoproteins such as AKT and MAPK. CONCLUSIONS: These findings demonstrate that OA, the main monounsaturated fatty acid of olive oil, suppresses Her-2/neu overexpression, which, in turn, interacts synergistically with anti-Her-2/neu immunotherapy by promoting apoptotic cell death of breast cancer cells with Her-2/neu oncogene amplification. This previously unrecognized property of OA offers a novel molecular mechanism by which individual fatty acids may regulate the malignant behavior of breast cancer cells and therefore be helpful in the design of future epidemiological studies and, eventually, dietary counseling.

PMID: 15642702 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_docsum


1: Med Hypotheses. 2005;64(5):997-1001. Related Articles, Links
Click here to read
Targeting fatty acid synthase-driven lipid rafts: a novel strategy to overcome trastuzumab resistance in breast cancer cells.

Menendez JA, Vellon L, Lupu R.

Department of Medicine, Evanston Northwestern Healthcare Research Institute, 1001 University Place, Evanston, IL 60201, USA. javiermenendez72@yahoo.com

Trastuzumab (Herceptin) is a humanized antibody directed against the extracellular domain of the tyrosine kinase orphan receptor Her-2/neu (erbB-2) that has shown therapeutic efficacy against Her-2/neu-overexpressing breast tumors. However, less than 35% of patients with Her-2/neu-overexpressing metastatic breast cancer respond to trastuzumab as a single agent, whereas the remaining cases do not demonstrate tumor regression. Furthermore, the majority of patients who achieve an initial response generally acquire resistance within one year. Therefore, the identification of the potential mechanisms of resistance to trastuzumab can be very helpful for the development of new compounds, which might overcome that resistance and/or have additive/synergistic antitumor effect when given in association with trastuzumab. Recent studies in breast cancer cells have revealed a bi-directional connection between Her-2/neu and fatty acid synthase (FAS), a major lipogenic enzyme catalyzing the synthesis of long-chain saturated fatty acids from the 2-carbon donors malonyl-CoA and acetyl-CoA. Her-2/neu overexpression stimulates the FAS promoter and ultimately mediates increased endogenous fatty synthesis, and this Her-2/neu-mediated induction of breast cancer-associated FAS is inhibitable by trastuzumab. On the other hand, chemical FAS inhibitors as well as RNA interference-mediated silencing of FAS gene repress Her-2/neu gene expression at the transcriptional level. Moreover, specific FAS blockade synergistically sensitizes breast cancer cells carrying Her-2/neu-oncogene amplification and/or overexpression to trastuzumab-induced cell growth inhibition and apoptotic cell death. Strikingly, FAS inhibition synergistically interacts with trastuzumab in Her-2/neu-negative breast cancer cells engineered to overexpress Her-2/neu, thus suggesting that the molecular linkage between FAS activity and functioning of Her-2/neu cannot be explained only on the basis of a transcriptional repression of Her-2/neu gene promoter. Interestingly, while in liver and adipose tissue FAS produces fat from excess carbon consumed as carbohydrates, which is ultimately stored as triglycerides, in epithelial cancer cells, FAS activity is mainly involved in the production of phospholipids partitioning into detergent-resistant membrane microdomains (lipid raft-aggregates), which point to an active role of FAS in the deregulation of membrane functioning in tumor cells. Importantly, clusters of Her-2/neu and EGFR (erbB-1) co-localize with lipid rafts and the lipid environment in the cell membrane of breast cancer cells profoundly influences their association properties and biological functions. We hypothesize that pharmacological or small interference RNA-induced inhibition of breast cancer-associated FAS will result in major changes in the synthesis of phospholipids which, in turn, should impair a correct cellular localization of Her-2/neu at the cellular membrane of breast cancer cells. In this working model, FAS inhibition could induce a shift in the equilibrium between transport of Her-2/neu to and from the membrane favoring an increased Her-2/neu internalization followed by intracellular degradation, thus enhancing the mechanism of action of the anti-Her-2/neu antibody trastuzumab. Moreover, the inhibition of FAS-driven lipid rafts will also negatively affect EGFR-Her-2/neu cross-talk, an important mechanism of trastuzumab resistance. In summary, the specific blockade of a novel molecular linkage between FAS-regulated membrane composition and functioning of transmembrane growth factor receptors EGFR and Her-2/neu may represent a previously unrecognized therapeutic approach circumventing trastuzumab resistance in breast carcinomas.

PMID: 15780499 [PubMed - indexed for MEDLINE]

[R.B.]

Here is a link to NCBI articles from a search on the general subject of fats HER 2 etc.

RB


http://www.ncbi.nlm.nih.gov/entrez/q...m_uid=15642702

[judiek]

Irene,


I am her2 negative so don't know all that much about herceptin and tykerb. I wanted to share with you my experience with avastin. I enrolled in the taxol and avastin trial in Jan of 2004 when dx with mets to lungs and liver. It did a great job for 15 months. I do know of other doing avastin with taxol, abraxane and navelbine. From what I have read and heard from others is that the avastin isn't doing a good job by itself...only with a chemo. So, if you're thinking about it as a single agent you may want to do more research on this. Hope this helps and I sure understand wanting to get started. I had to wait three weeks to start on the taxol and avastin trial when first dx with mets...I was so scared. The doctor told me that if the treatment was going to work now it would still work in 3 weeks...I waited it out and was very happy. It's a tough decision...best of luck to you
Warmly,

Judiek

[R.B.]

Re previous posts - omega six pathways cox 2 etc


Blood supply to tumour new vessel growth and cox 2

and a link to an extensive list of trials on the subject on just one search. A common factor in a wide range of cancers?

PGE2 is a product of omega six. Omega three and six fats are included as building blocks in cell membranes. They are included essentially in the proportions ingested

Lets call omega threes white and sixes red, think of it as a rather odd football game. My understanding is that when the body sends out an alert, infection, insect bite etc. the team manager will just ask for a number of players (lets say 100 for illustrative purposes). So 100 players will come off the bench (the membrane). The number of red and white players on the bench is dependent on the number you have chosen by eating them. Lots of omega six = lots of red players on the bench. Alert, players come off bench, red swamp whites in numbers. The result is a red type game. Inflamation and not enough white players for a "fair game" and to keep the red in check, and come to an end of the game. The result can be permenant low level inflamtion between the main games.

From what I read it appears that over time the team manager has just got used to assuming that the red and white teams will always be balanced, and has never learned to balance the teams when they are not. The mangager just ask who ever is sitting there to join the game and becuse we eat more white than reds in general terms the game is always skewed towards the reds.

So it is down to us to make sure that the players are within reasonable limits balanced enough to provide a balanced game.

It is obviously much more comlex than this I am simply trying to explain my limited and rather amateur understanding of why altering the balance of intake of fats can influence the shape of the game.

http://www.ncbi.nlm.nih.gov/entrez/q...m_uid=11688844

RB



http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_docsum


1: Ann Clin Lab Sci. 2001 Oct;31(4):325-48.Click here to read Links
Review: molecular pathology of cyclooxygenase-2 in cancer-induced angiogenesis.

* Fosslien E.

Department of Pathology, College of Medicine, University of Illinois at Chicago, 60612, USA. efosslie@uic.edu

Cancer-induced angiogenesis is the result of increased expression of angiogenic factors, or decreased expression of anti-angiogenic factors, or a combination of both events. For instance, in colon cancer, the malignant cells, the stromal fibroblasts, and the endothelial cells all exhibit strong staining for cyclooxygenase-2 (COX-2), the rate-controlling enzyme in prostaglandin (PG) synthesis. In various cancer tissues, vascular endothelial growth factor (VEGF) and transforming growth factor beta (TGF-beta) co-localize with COX-2. Strong COX-2 and VEGF expression is highly correlated with increased tumor microvascular density (MCD); new vessels proliferate in areas of the tumor that express COX-2. Moreover, high MVD is a predictor of poor prognosis in breast and cervical cancers. COX-2 and VEGF expression are elevated in breast and prostate cancer tissues and their cell-lines. In vitro, PGE2 induces VEGE Supernatants of cultured cells from breast, prostate, and squamous cell cancers contain angiogenic proteins such as COX-2 and VEGF that induce in vitro angiogenesis. A selective COX-2 inhibitor, NS-398, restores tumor cell apoptosis, reduces microvascular density, and reduces tumor growth of PC-3 prostate carcinoma cells xenografted into nude mice. The COX-2 produced by a malignant tumor and COX-2 produced by the surrounding host tissue both contribute to new vessel formation, which explains how selective COX-2 inhibition reduces tumor growth where the tumor COX-2 gene has been silenced by methylation.

PMID: 11688844 [PubMed - indexed for MEDLINE]

[Patty H]

I know how you feel. I have been off chemo a year now. I had a pet scan in Dec. which was pretty good. But then I had one in June which shows a 2.2 c. leision on my hip. This grew since the last pet. We are trying to get the tykerb which seems to be taking for ever. I saw my Dr. yesterday and he doesn't want to start me on anything else since it could keep me from getting the tykerb. I am leaving on a cruise in 3 weeks. But it is kind of scarey knowing that my lung met is growing and the one on my hip is too. I think how long should I wait.

Patty H

[R.B.]

If you have any questions on the three six issue please come back.

To be boring it is key to look at intake on a full and logical basis with nothing excluded.

We are so used to considering polyunsaturates as good. I just had a long converstaion with some one on the subject of three sixes and asthma - "oh I just use olive oil"..... further inquisition ...further inquisition..oh "I use grapeseed to cook my meat, but.... they said.

I explained grapeseed was very high in sixes.

I will let you know if their child's condition improves with a keen eye on sixes and some added falxseed and fish oil.

RB

[al from Canada]

Irene,
There is another option which may work well for you.... pertuzumab is an monoclonal antibody which works independantly of herceptin + and is also an EGFR (HER1) and HER3 inhibitor, and the good news is that it is also made by Genetech and the trial allows herceptin with it. I would be tempted to look at this before tykerb.
http://www.clinicaltrials.gov/ct/show/NCT00263224
good luck,
Al

[al from Canada]

and for those not familiar with pertuzumab (omnitarg):
http://www.csmc.edu/pdf/jco2005232534agus.pdf
Al