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

[Barbara H.]

Irene,
When you speak with your oncologist I would tell him about how much this trip means to you and see if he can devise a treatment that includes your trip to Italy. Your state of well-being also affects your immune system and plays a part in fighting this disease. I feel that the trip would be beneficial in more ways than one.
Best wishes and I really hope you are able to go.
Barbara H.

[IRENE FROM TAMPA]

although I am not sure that I completely understand everything on those web sites.

I do take some Omega 3 supplements but I do not take the 6. I have cut back on alot of the supplements my nutritionist had me on, mostly because of the cost and concern of interference with the chemo's. I now take your basic multi vitamin, calcium, and Omega 3. I always say that I would be healthy as a horse if it wasn't for this $$@#@ cancer.

I am of Mediterranean ancestry so my cooking does include lots of olive oil and garlic and I try to eat a well balanced variety of foods. I do know that the core of our immune systems come from our digestive tracts so it's important to try to retain the GOOD bacterial since these chemo's do a good job of killing them off.

I have also been checking on all of the side effects of the Avastin drug and trying to get as informed as I can before I make a decision (thanks for the web site) which when I read them I had a few WOWS come out of my mouth (plus a few other choice words) It's like those commercials that you see on T.V. When they finish listing all of the side effects you wonder who in the world would even take them to begin with.

The drug does sound promising though since it is designed to stave off the blood supply to the tumors and that is what I believe needs to happen to hopefully destroy them. Now if it will work or not, that I guess is what we need to find out in those trials.

I really do appreciate you husbands/partners doing so much research for us.
I love this site for that very reason. I know that when I need information on something or some advise, I can sign on and just ask.

Thanks for all that you men do. We know that your job as a caregiver is not an easy one and your support is very important.

Good luck to your wife and please keep me posted as to her progress.

[IRENE FROM TAMPA]

I totally agree with you as I think it would be healing to the mind and soul to get away.

Actually, my onc. really wants me to make this trip and was hoping I could get on the Tykerb/Xeloda trial which is being offered in Tampa. They are both pill forms so she figured this would be great as I could carry them with me and stay on a treatment.

I am waiting to see how long it will take them to get up an running and meantime I am keeping my options open by checking on different trials close by to fall back on. As I am finding out (I have been on the phone all day today) checking on options, that my waiting time will probably be about 3 weeks either place I go to, and since I think I have already exhausted all of the regulare chemos out there I may not have a choice but to wait to try one of the trials. Knowledge is power so I will keep on checking out as much as I can this week end and try to make a decision by next week when I see my onc. on Wednesday.

Thank you so much Barbara for your support.

[Cathya]

Irene;

I agree with the others that your attitude has always been an inspiration and I sorely wish that circumstances were different for you. I do not have experience with these drugs but I keep thinking of comments made by Lyn and am concerned that if you delay in any way taking treatments these tumors might totally get away from you. So, I guess I'm in the Avastin court. I personally have had the impression that at this point one would be wisest to totally surround and attack the cancer from all angles....that is......what would be wrong with using herceptin, lapatinib and avastin at the same time. I realize that you would have a wait a bit for the lapatinib but couldn't you go ahead with the avastin and stay on the herceptin?

Cathy

[Lani]

Are you ER or PR + You did not mention an AI, so I assume you are not. According to Drs. Spector and Bacus, who authored the article those who become resistant to Tykerb do so via the ER pathway, so if you are ER or PR +, you would have to be on Fulvestrant or an AI to help prevent that. If you are negative, you would not have to worry about that avenue of resistance.

As Becky said, Avastin remains available to you for the future anyway, since is FDA approved for other uses and can be used off-label.

I would hope they would reevaluate you with scans etc very frequently to allow you to switch to/add on Avastin quickly should the Tykerb not do the trick.

A paper was given at ASCO (or was it a poster) on what moledular tests on your original tumor would predict Tykerb efficacy--perhaps Becky or someone else who was at ASCO has the source--perhaps Targeted Molecular Diagnostics could test those markers. They usually give results in less than a week after a sample is received I think.

Good luck!

[Sheila]

Irene
It sounds like Herceptin alone isn't doing it...that would make me want to see you get into the Tykerb Xeloda trial...and that would be so easy to take "on the road." But then there is the wait which makes me say go for the Avastin since it helped before....this disease never gives us any clear cut answers! I hope everything goes well so you can enjoy this trip...when I went to the Keys the beginning of June it was only 4 days but it was 4 days that I didn't think about cancer....even while I popped the Xeloda 2x a day! By the way, Xeloda is very easy for me to take....I have had no problems with 2500 mg a day.

[R.B.]

Re omega threes

DHA particularly and EPA are only found in limited foods fish oil being one of them.

From the trials DHA appears to be an important factor.

The body does not make it easily at the best of times.

http://www.ajcn.org/cgi/content/full/77/1/226

High sixes are found in most vegetable oils (virgin olive is one exception only about 10% six) and flax seed which is lowish in six and high in three.

You might want to show your nutritionlist onc the Greek diet post and ask him or her their thoughts, particularly the later trials on DHA and cox inhibitors / intravenous fish oil based nutrition - re inflamatory factors etc.

I would be interested in their reaction to the results of the trials.

I have also posted a trial listing synergies between omega three and various chemos.

I think I have seen a suggestion threes may help stop resistance to Herceptin, but am not certain. I have looked previously but will look again.

You can get tested for the levels of threes and sixes.

Reasons for posting - I am not a carer - and not married - a mix of reasons - previous association - my conviction that BC at least in part is part of wider western loss of health and that excess six and lack of three plays a large part ( which includes lack DHA EPA and body failings to make - it looks like this may be due in part to excess six and in part to trans fats and I guess increased uses of cox blockers asprin etc) - it keeps me busy - and it is rewarding and motivating to feel of some use now and then.

From a different perspective Smart Fats M Schmidt sets out some of the wider implications of the western diet on humanity - some of which had begun to form in my much more limited knowledge space - implications include a string of diseases, increased aggression, mental issues, ADHD etc in children, obesity, long term intelligence - (in animals deprived of EPA DHA omega three number of brain cells drops each generation) ............. far worse as a comparison comparison than smoking.....potentially unecessary suffering???...... I just hope it does not take as long for the message to get across. I would put a health warning on all products containing trans fats and high six vegetable oils if I could wave a magic wand.

The portrait of the scream comes to mind - omega six she shouts mixed with images of pain.

Please do have a look at the trials at the end of the Greek Diet post, on the edge but if the options are running out maybe at least asking your advisors / nutritionalist what they think of them even as adjuvant.

This article was thought provoking in its implications if you did not see it.

http://www.cabnr.unr.edu/cabnr/newsl...nandcancer.pdf

And adjuvant or in any combination the side effects of omega three DHA should not require any understandable expletives.

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]