for Chelee, Ceesun...hot off the press NY Times herceptin+tykerb great results!

[Lani]

Novel Drug Combo Extends Breast Cancer Survival


By THE ASSOCIATED PRESS
Published: December 11, 2009
Filed at 1:35 p.m. ET

SAN ANTONIO (AP) -- Women with very advanced breast cancer may have a new treatment option. Doctors say that a combination of two drugs that more precisely target tumors significantly extended the lives of women who had stopped responding to other treatments.

The study is the first big test of combining Herceptin and Tykerb (TIE-curb). In a study of 300 patients, women receiving both drugs lived 20 weeks longer than those given Tykerb alone. Doctors expect the combo to make an even bigger difference for women with less advanced disease.

The medicines aim at a protein that is made in abnormally large quantities in about one-fourth of all breast cancers. One drug blocks the protein inside a cell and the other does the same on the cell's surface.

[Ellie F]

Thanks Lani
We suspected this may be the case given the response of some of our sisters on the board. It seems this combo and T-DM1 are making significent advances for mets.
My only concern is that for women here in the UK this will NOT be an option as NICE will not approve tykerb.
Ellie

[Chelee]

Lani, You beat me to it! I just posted about the same thing...had I saw your post first I wouldn't have posted about the Tykerb/Herceptin combo.

I was just so thrilled to see it because it was so frustrating to have my onc...and especially the City of Hope onc that has such an impressive backround not know anything about this combo when I mentioned it to her over 2 months ago. Both onc's were so adamant that this combo would not, and could not work without a chemo drug thrown in there. I told her I got my information straight from the man himself...Dr. Slamon. (What more did I need to say?!) Both onc just raised the eyebrows like they had no clue why Dr. Slamon would even suggest this. I am so happy to see this news come out. Can't wait to take a copy to my onc this coming Monday. (She will probably already of gotten wind of it by then...but just in case I will be prepared)

Thanks for posting this...I know so many that were looking forward to hearing news on this combo.

Chelee

[michka]

20 weeks.... I know progress is only one small step after another and added up, it makes the difference but I dream to read 20 months, 20 years. I must be depressed. Michka

[Ceesun]

thanks for the info and update--had my benadryl and vitamin h (per Andi) Thursday--seems like old times! Ceesun

[gdpawel]

Targeted therapies are typically not very effective when used singularly or even in combination with conventional chemotherapies. The targets of many of these drugs are so narrow that cancer cells are likely to eventually find ways to bypass them. Durable responses are rare and no one with advanced cancer has yet to be cured with targeted therapy. Physicians may have to combine several targeted treatments to try an achieve cures or durable responses.

So, some clinical studies are trying to delineate the benefit achieved when combining two innovative targeted treatments together. However, these targeted therapies produce limited results because they can help a relatively small subgroup of cancer patients, and tests to pinpoint those patients are desperately needed. The trick is figuring out which patients will respond. The challenge is to figure out which patients to give them to. There is a targeted assay to match targeted cancer therapies to those cancer patients.

The targeted assay uses "whole cell profiling" which is a variety of metabolic (cell metabolism) and morphologic (structure) measurements to determine if a specific drug is successful at killing the patient's cancer cells. Whole cell profiling measures genes before and after drug exposure. It makes the statistically significant association between prospectively reported test results and patient survival.

And it is the only cell-death endpoint assay system in which drug effect upon cancer cells is visualized directly. Photomicrographs of actual tumor cells show the condition of cells as they are received and enriched in the lab, and also the conditions of control cells post-culture. In this visualization, the microscopic slides sometime show that the exact same identical individual culture well, shows some clusters have taken up vast amounts of the molecular drug, while right next door, clusters of the same size, same appearance, same everything haven't taken up any of the drug.

It doesn't matter though if there is a target molecule (protein or receptor) in the cell that the targeted drug is going after. If the drug either won't "get in" in the first place or if it gets pumped out/extruded or if it gets immediately metabolized inside the cell, drug resistance is multifactorial. The one advantage of whole cell profiling is that it can show this at the cell "population" level, measuring the interaction of the entire genome.

This could help solve the problem of knowing which patients can benefit from these molecular drugs. Afterall, these "smart" drugs do not work for everyone, and a test to determine the efficacy of these drugs in a patient could be the first crucial step in personalizing treatment to the individual.

Literature Citation: Weisenthal, LM, Patel, N, and Rueff-Weisenthal, C. Cell culture detection of microvascular cell death in clinical specimens of human neoplasms and peripheral blood. J Intern Med 264:275-287, September 2008

[Rich66]

I'm sure that 20 week figure is an average and some may get tremendous, long term benefit. One part of their benefit may be because they are thought to be effective on cancer stem cells.
Having a better idea what might work (or what won't) through cell analysis sounds great. But kind of limited in terms of the biopsy process and heterogeneity of samples within a tumor much less multiple tumors in different locations.
Perhaps simultaneously targeting multiple receptors, cell phases and more fundamental processes like glycolysis and the immune system can give cancer fewer ways to thrive. Maximizing the delivery through metronomic and chrono-modulated delivery, as well as removing conflicting drugs like steroids and opiates/opioids might give more than incremental benefit.
Just have to find a doc who puts it all together.

[gdpawel]

According to Dr. Arny Glazier, a cancer researcher, in his book Cure: Scientific, Social and Organizational Requirements for the Specific Cure of Cancer," the consistent and specific cure or control of cancer will require multiple drugs administered in combination targeted to abnormal patterns of normal cellular machinery that effect or reflect malignant behavior. Finding the 'patterns' of malignant cells and developing a set of 5 to10 drugs in order to cure or control cancer."

So the consistent and specific cure of cancer requires therapy that can target the set of "all" malignant cells that could evolve in the human body. It is thought that each anti-cancer drug needs to be given at a dose sufficient to kill cells that express the pattern targeted by the individual drug. In order to kill "all" patterns of malignant cells, you need to give full doses of all drugs (5-10) in combination.

However, it is not possible to give five to ten existing drugs together in combination, the toxicity would be prohibitive. They have overlapping toxicity, which means you need to cut the doses when you give them together, so you get down to homeopathic dose levels.

This could be overcomed with potentiation therapy (IPT) or low-dose chemotherapy, which makes cell membranes more permeable and increases uptake of drugs into cells. IPT selectively targets tumor cells, which usually have more insulin receptors than normal cells. Makes tumor cells more susceptible to chemo by modifying cell metabolism. As a result, cancer patients can greatly reduce chemo dosage (reduce it to only 10-15%), while at the same time, receive the 5-10 drugs in order to effectively cure or control cancer, and eliminate most side effects while increasing the effectiveness of chemo (chemo synthesizer).

Given the current state of the art, in vitro drug sensitivity testing could be of significant clinical value. Upgrading clinical therapy by using drug sensitivity assays measuring "cell death" of three dimensional microclusters of live "fresh" tumor cells, can improve the situation by allowing more drugs to be considered. The more drug types there are in the selective arsenal, the more likely the system is to prove beneficial.

Cell culture assays tests with cell-death endpoints are the Rosetta Stone which allows for identification of clinically relevant gene expression patterns which correlate with clinical drug resistance and sensitivity for different drugs in specific diseases. There is no single gene whose expression accurately predicts therapy outcome, emphasizing that cancer is a complex disease and needs to be attacked on many fronts.

A number of cell culture assay labs across the country have data from tens of thousands of fresh human tumor specimens, representing virtually all types of human solid and hematologic neoplasms. Cell culture assay labs have the database necessary to define sensitivity and resistance for virtually all of the currently available drugs in virtually all types of human solid and hematologic neoplasms.

The consistent and specific cure or control of cancer will require developing a set of drugs, given in combination, targeted to patterns of normal cellular machinery related to proliferation and invasiveness. These requirements define a rational, practical strategy to develop curative therapy for all forms of solid cancer.

Source: http://www.lulu.com/content/276115

[Ellie F]

Hi Guys
Let me see if I'm following this correctly.
The argument seems to be that if we could precisely define the various pathways in individual tumours we may then have a fighting chance of a cure. Restricting this is the need to give a multiplicity of different targeted therapies and chemo which would be so toxic it would kill the patient! Some labs however already have this info but it needs assimilating.
Am I on the right track??
What about naturally occurring substances eg turmeric,vit D3 etc
Ellie

[Rich66]

Using natural substances therapeutically seems just as logical as using designated therapies if there is sufficient understanding of how they work and interact. That's a core principle of an "integrative" combination of the best of conventional and "alternative" therapies. Even more conventional oncology is embracing some of this, albeit indirectly and slowly.
IPT seems interesting. Currently no reimbursement for it and some questionable practitioners using it. Not saying there isn't something behind it and still could be worth paying out of pocket for. Just that it's significantly out of the main compared to metronomic or chronotherapy. There seems to be ever growing research support for metro and chrono..but the typical delivery system has a hard time accomodating/reimbursing doctors for them.
But you know, Ellie, I still wonder if LIFT has the potential to cure or manage the cancer by itself. Would sure like them to reveal the results for the few getting it as we speak (type). Oops. Looks like we're getting far off the original thread. But hey..Tykerb and Herceptin can certainly play a role for those it applies to. Just can't help but yearn for a more comprehensive strategy.

[Ellie F]

Hi Rich
I suspect LIFT has the potential just not the backing to move it ahead fast enough! The other immunotherapy trials are also very encouraging and I wait with baited breath for the reports from Roger Williams!
As some people are 'cured' of bc is it reasonable to assume that the chemo worked so well that it killed all the cells or that enough were killed for their own immune ststem to mop up the rest? Or that they won the lottery and the chemo they were given was exactly the right 'match' to kill their cancer cells?
More questions than answers again!Meanwhile will go and take my olive oil
Ellie

[Rich66]

Maybe they got the right match for their cancer. Maybe they got the chemo at the right time of day. Maybe they had a stronger immune system going in and stayed on schedule for an extended period. Roger Williams?

[gdpawel]

The best combinations are those in which there is true synergy and in which the toxicities of the drugs in the combination are non-overlapping, so that full doses of each drug may be given safely.

True synergy is rather uncommon in most adult solid tumors. Most drug combinations in diseases such as cancer are merely additive, where the whole equals the sum of its parts, and not synergistic.

In cases where drugs are only additive and not synergistic, nothing is learned by testing the drugs in combination over what is learned by testing them separately. So drugs in combination are only tested in cases where there is the realistic possiblity of seeing true synergy.

The theory behind combination chemotherapy is that you can't give full doses of all drugs when you give them together. They have overlapping toxicity, which means you need to cut the doses when you give them together, so you get down to "homeopathic" dose levels.

Over the last few years, functional assays have revealed synergy with some combination targeted agents, like Herceptin and Tykerb.