PS I forgot this about Avastin
http://www.cancer.gov/clinicaltrials/results/bevacizumab-and-colorectal-cancer0601
Other clinical trials have shown that a different treatment approach known as FOLFOX (oxaliplatin plus
fluorouracil plus leucovorin ) produces a similar improvement in survival compared to IFL, and is
currently used as the standard therapy for colorectal cancer patients.

So it seems to be saying that if that's the best you got with Folfox, you cannot expect better with
Avastin?
J

Hello Holden, Now I'm worried about Joe, haven't heard back.
Also wondering what your interpretation of "first line treatment" is?
(Perhaps steph will explain)
I thought it means "haven't had any other chemo before", OR the best chemo
for the cancer/stage.
If the former, he would not be eligible for Avastin?
I think Joe has to do clinical trials, if I recall (due to finances, but I
could be wrong on that).

If you run into him, please send him my best wishes and hugs.

J - Hoping for an update

Accidental find...<no date on this article>
http://ovariancancer.jhmi.edu/recurrentqa.cfm
So what are the potential applications of these angiogenesis inhibitors in combination with chemotherapy?
The biologics probably aren't going to be very good at shrinking down bulky tumors, but again, with ovarian
cancer, there is the luxury with most patients, that at some point in time, they will be in a pretty good
remission with low volume and usually nondetectable disease. So the issues are, if chemotherapy is combined
with these, can we prevent that last .1% of cancer cells and prevent a recurrence? These could potentially
be used as either consolidation or maintenance after initial therapy instead of combining them to use them
sequentially. It might be possible to use them as primary treatment for low volume or microscopic disease,
and certainly for women who are felt to be at high risk. Maybe ultimately, these will be able to be used as
a preventive agent.

However, there are potential problems. When you interfere with the formation of blood vessels, you may
interfere with healing. So, certainly after a surgery this is probably not an appropriate thing to use. In
patients who have infections and have to heal, these may be problematic. There has been a higher instance
of vascular events, blood clots, phlebitis, etc. There's also a concern if blood vessels are blocked;
remember that chemotherapy drugs by and large get to tumors by blood vessels, that if you block blood
vessels, maybe you'll have antagonism. Maybe you'll prevent the chemotherapy drugs from getting to them.
So, again, we have to proceed cautiously in the trials with these agents.

One of the things that we know in cancer cells is that cancer cells have a number of genetic mutations. By
and large, the genetic mutations in cancer cells are characterized as oncogenes or tumor suppressor genes.
Cancer is highly associated with oncogenes, which are genes that cause cells to grow. These genes are
either overactive or in excess. Tumor suppressor genes stop cells from growing. Their loss is associated
with cancer.

Bert Vogelstein at our institution elucidates oncogenes and tumor suppressr genes with an analogy of a car:
Oncogenes are like the gas pedal in the car, tumor suppressor genes are like the brake pedal. If your gas
pedal gets stuck, your car will keep going even though we know that intermittently, your car should stop.
These oncogenes activate cells to multiply. Tumor suppressor genes do the opposite; they're analogous to
the brake pedal in our car. When tumor suppressor genes are lost, their normal function, stopping cell
growth, is lost. In cancer cells, both of these usually occur. There are overactive oncogenes, as if the
gas pedal is stuck, and you lose tumor suppressor genes, as if the brake pedal doesn't work. And that's
really what happens in cancer. In gene therapies, what we're trying to do is reintroduce these normal tumor
suppressor genes. In cancer cells, though, what we recognize is that many of the normal genes in the cell
have amplified these oncogenes, which may be targets for therapy.

This scheme just shows you the normal cells. What you can see is that there are a whole variety of these
oncogene products, things that you all may have read or heard about. They can be in the nucleus, they can
be in the cytoplasm of the cell, or they can be in the membrane of the cell. When they're in the membrane
of the cell, they usually have something that binds to them and that transmits a signal to the nucleus that
says replicate the DNA and grow. One of the things that we know in these cells is that when you have a
growth factor receptor (remember, these are things that stimulate cells to grow) that this is like a lock
and key. When you have the lock in the tumor cell and the key comes around, which is the growth factor, it
binds and it transmits that signal to the nucleus that says to grow. Not only in some cases do we have
extra keyholes made, extra locks made, but sometimes tumor cells will also make extra keys. They'll make
extra growth factors and extra growth factor receptors. This is that vicious cycle where a tumor cell can
continuously be telling itself to grow over and over again. One of the things we're trying to do is to
interrupt that signal. [end copied text]
J