While I know screening can be the biggest prevention of this disease,
I want to make everyone aware of a new vaccine that is on the verge of
replacing chemotherapy. The name of the vaccine is OncoVAX
(<http://vaccinogeninc.com/oncovax.html>). It is from a company called
Vaccinogen (<http://www.vaccinogeninc.com/index.htm>).

This vaccine is available to anyone that has been diagnosed with Stage
II colon cancer and HASN'T had surgery. Currently this vaccine is only
available commercially in Europe but arrangements can be made for the
patient to have surgery in the United States, which would possibly be
covered by insurance, but the OncoVAX treatment itself will be out of
pocket. Following surgery, a patient-specific vaccine is made from the
patient's resected tumor that when injected back into the patient
decreases the chance of the cancer returning from 1 in 3 to 1 in 10.
These are odds everyone should be aware of.

i had 4 polyps found and removed after my dr insisted i have a
colonoscopy after having salmonila poisoning. 3 of the polys were
precancerous. have not had another, how often should i have one done
and how often do they reoccur or more develope ?

Dr Amod Tootla renowned cancer colon surgeon, board certified to
practice in 20 counties and is also rated one of the top 2000 scientists
has 1000 patients using this unconventional therapy.

check out the product at:

www.foreverwithmangosteen.com

Send away for a free CD from Dr Tootla called "Straight Talk"

Write to:

Tim@...

Hi Ed,
Yes, I have much information on this. If you or anyone else would like
to find out why over 500 Doctors have thousands of patients on this
product, and are finding success in fighting and preventing disease
with this please let me know.

Thanks
Tim





--- In experimentalandunconventional@yahoogroups.com, "edsmav"
<edsmav@...> wrote:
>
>
> Well, just put "mangosteen colon cancer" (without the quotes) into
> Google  ( http://www.google.com/ ),and look over the refs.for a start
> anyway.
>
>                                Regards,
>
>                                           Ed
>

The site where you can listen to this top cancer doctor is
www.transferfactorproduct.info/4life .If the link doesnt work, type
the address into your address bar and it should bring it up. There
has been a big break through recently in addition to this info to
make things more effective. Can elaborate more after you listen to
Dr. Townsend. If you have problems listening to the Dr, or want to
know how to try this companies products risk free, let me know and I
will tell you how to become a preferred customer.    --- In
experimentalandunconventional@yahoogroups.com, Tom Hennessy
<tom_hennessy2000@...> wrote:
>
> I'm interested
>
>
> ----- Original Message ----
> From: thom8869 <thom8869@...>
> To: experimentalandunconventional@yahoogroups.com
> Sent: Friday, September 14, 2007 4:06:00 AM
> Subject: [Experimental and Unconventional] What this Top M.D. did
when he had cancer and now recommends to Patients
>
> If interested in finding out how this top medical doctor beat his
> cancer and now what he recommends to all his patients for treatment
and
> also preventative treatments,email me and I will send you his link
or
> his cd,whichever you prefer. thom8869.
>
>
>
>
>
>
______________________________________________________________________
______________
> Check out the hottest 2008 models today at Yahoo! Autos.
> http://autos.yahoo.com/new_cars.html
>
> [Non-text portions of this message have been removed]
>

Hey, Ed,

   It's good to know you're still out there watching over all of us. :)

   Denise

edsmav <edsmav@...> wrote:

Well, just put "mangosteen colon cancer" (without the quotes) into
Google ( http://www.google.com/ ),and look over the refs.for a start
anyway.

Regards,

Ed






---------------------------------
Fussy? Opinionated? Impossible to please? Perfect.  Join Yahoo!'s user panel and
lay it on us.

[Non-text portions of this message have been removed]

Well, just put "mangosteen colon cancer" (without the quotes) into
Google  ( http://www.google.com/ ),and look over the refs.for a start
anyway.

                                Regards,

                                           Ed

My mother was diagnosed with Colon cancer 5 years ago after surgery and
chemotherapy it went into remission only to return 2 years later. It
then went into remission and last year found that it had spread to her
lungs. When she got cancer the first time they gave her 24 months to
live, thank god we still have her 5 years later. She started taking
Mangosteen about 4 months ago and when she went for her last scan many
of the tumors had either shrunk or disapeared alltogether. We are very
excited, but cautious. Does anyone else have any info on this product?

Thank You

I'm interested


----- Original Message ----
From: thom8869 <thom8869@...>
To: experimentalandunconventional@yahoogroups.com
Sent: Friday, September 14, 2007 4:06:00 AM
Subject: [Experimental and Unconventional] What this Top M.D. did when he had
cancer and now recommends to Patients

If interested in finding out how this top medical doctor beat his
cancer and now what he recommends to all his patients for treatment and
also preventative treatments,email me and I will send you his link or
his cd,whichever you prefer. thom8869.





      
________________________________________________________________________________\
____
Check out the hottest 2008 models today at Yahoo! Autos.
http://autos.yahoo.com/new_cars.html

[Non-text portions of this message have been removed]

If interested in finding out how this top medical doctor beat his
cancer and now what he recommends to all his patients for treatment and
also preventative treatments,email me and I will send you his link or
his cd,whichever you prefer. thom8869.

My brother in-law was diagnosed with colon cancer, which has at this
point metastasized.  We live in NY and someone reccomended Dr. Mitch
Gaynor, for his approach to combining western and alternative medicine.

I wanted to find out if anyone has heard of him and has any
information to share or perhaps if there are other doctors that
someone can reccomend.

Any help would be greatly appreciated.

Thanks,

Alla

Welcome to the group, though I'm sorry you have to be
here.  I had Xeloda, 6000 milligrams a day when I took
it, and had serious hand and foot syndrome, got
oxaliplatin every two weeks but the cold sensitivity
went away in between.  I haven't gotten the Avastin
yet, hopefully not for a long time as right now I have
no evidence of disease.  I've been off those drugs for
a year now and have no neuropathy or lingering side
effects.  I know there are some here who are having
similar problems, I'm sure they'll be along soon to
give you some ideas about what to do for it.

Denise

--- maartenaleman <maartenaleman@...> wrote:

> I am from the Netherlands. Colon cancer (Dukes IV)
> was discovered in
> Febr. 2006.
> I was treated with Oxaliplatin (4 months),
> Capecitabine (Xeloda) 6
> months, and 18 times with Bevacizumab (Avastin)
> during 57 months.
> De growth of the tumor and the metastasen has
> allready stopped for
> about one year, but it is still there in reduced
> form in the colon and
> in the liver. The last months I got problems with
> peripheral neuropathy
> so that the hospital also stopped with the Avastin.
> Has anyone the same experience. What can be done
> about the neuropathy.
> My oncoloog gives me medicines but they do not help
> much. I would like
> to hear from anyone simular or other experience and
> perhaps also a
> solution for the neuropathy. May the Lord bless you
> all.
>
>




________________________________________________________________________________\
____Luggage? GPS? Comic books?
Check out fitting gifts for grads at Yahoo! Search
http://search.yahoo.com/search?fr=oni_on_mail&p=graduation+gifts&cs=bz

I am from the Netherlands. Colon cancer (Dukes IV) was discovered in
Febr. 2006.
I was treated with Oxaliplatin (4 months), Capecitabine (Xeloda) 6
months, and 18 times with Bevacizumab (Avastin) during 57 months.
De growth of the tumor and the metastasen has allready stopped for
about one year, but it is still there in reduced form in the colon and
in the liver. The last months I got problems with peripheral neuropathy
so that the hospital also stopped with the Avastin.
Has anyone the same experience. What can be done about the neuropathy.
My oncoloog gives me medicines but they do not help much. I would like
to hear from anyone simular or other experience and perhaps also a
solution for the neuropathy. May the Lord bless you all.

Hi, everybody,

Thanks for allowing me to join and nice to meet all of you!
I was going to write and introduce myself a bit until I came across
something a friend emailed me that I want to pass along--The FDA is
about to make nutritional supplements inaccessible and there are only
8 days left to take action to stop it.

Sincerely,
Adam H.

Scott Darby <darby700@...> wrote:

     Date: Sun, 20 May 2007 23:37:23 -0700 (PDT)
     To: "Adam R. Huckins" <oakland_baseball@...>

     The FDA is about to promulgate* a rule whereby all natural
supplements and substances, including water in some cases,  will
become regulated drugs which you will be able to obtain only by
prescription from an allopathic doctor
     (an M. D.)   Your right to treat yourself, take what you want when
you want,
     to control your own body in this way will be violated.

     http://www.wnd.com/news/article.asp?ARTICLE_ID=55403

     This is quite an emergency.  We need to call our Congresspersons
and Senators
     quickly to stop this--and it absolutely has to be stopped.  FDA
also has a comment period until May 29; the phone number is
1-800-216-7331.
     The case docket number is 2006D-0480; it should be mentioned when
calling.
     There is also a comment form at:


http://www.accessdata.fda.gov/scripts/oc/dockets/comments/COMMENTSMain.CFM?EC_DO\
CUMENT_ID=1451&SUBTYP=CONTINUE&CID=&AGENCY=FDA

     All individual choice and natural treatment options will be gone
if this rule goes into
     effect.  The supplement industry that millions depend on for
natural health options
     will go out of business almost overnight.
     The supplements available then will only be ones made by
pharmaceutical
     companies, and will likely be of extremely poor quality.

     Phone numbers for your Reps. and Senators and the President are below,
     or you can get them at at www.house.gov ,  www.senate.gov , and
     www. whitehouse.gov

     Even if the rule goes into effect, Congress can pass a law
     overturning it at any time, so it's still very much worth
contacting your
     representatives in Washington.


     Call YOUR Congressman
     at 866 340-9281
     1-800-833-6354
     1-877-762-8762
     1-866-808-0065
     1-888-355-3588
     1-866-220-0044
     NOW!

     Call THE President
     at 202 456-1111
     NOW!
     Find Your Elected Officials and
     send a message from this web page:
     http://capwiz.com/jbs/home/


     Sample letter or email to Congress:

     The FDA is about to promulgate* a rule whereby all natural
supplements and substances, including water in some cases,  will
become regulated drugs which we will be able to obtain only by
prescription from an allopathic doctor
     (an M. D.)   Our right to treat ourselves, take what we want when
we want, to control our own body in this way will be violated.

     This is quite an emergency, and it absolutely has to be stopped.
     The case docket number is 2006D-0480

     All individual choice and natural treatment options will be gone
if this rule goes into effect.  The supplement industry that millions
depend on for natural health options will go out of business almost
overnight.
     The supplements available then will only be ones made by
pharmaceutical companies, and will likely be of extremely poor quality.

     Even if the rule goes into effect, Congress can pass a law
     overturning it at any time.  I ask that you introduce legislation
to stop the FDA from doing this, now or ever.

     Sincerely,
     (your name)



     *Promulgation (of executive branch rules): an unconstitutional
process where Congress long ago illegally delegated its lawmaking
power to executive branch agencies, such as the FDA, which issue
regulations having the force of law.

     The legislative power was granted to Congress in the Constitution,
not the Executive Branch, which the FDA is a part of. Congress should
make its OWN "comment" to the FDA!

NICE publishes final guidance on bevacizumab and cetuximab for the
treatment of metastatic colorectal cancer

The National Institute for Health and Clinical Excellence (NICE) has
today published final guidance on the use of bevacizumab and cetuximab
for the treatment of metastatic colorectal cancer.

The guidance does not recommend the use of these drugs for first line
therapy for metastatic colorectal cancer (bevacizumab) and therapy
following the failure of an irinotecan containing chemotherapy regimen
(cetuximab) and means that the joint appeal by Bowel Cancer UK and
Cancerbackup and the appeal by Merck Pharmaceuticals have not been
upheld.

Commenting on the guidance, Peter Littlejohns, Clinical & Public
Health Director, said : " The decision of the Appeal Panel means that
the recommendations set out in the final appraisal determination will
form the Institute's guidance to the NHS in England and Wales. The
kinds of decisions the Institute is asked to make are amongst the most
difficult in public life. Those who form our advisory committees are
acutely aware of the responsibility they carry and they form their
recommendations with great care. In this case, our advisory committee
was certainly aware that colorectal cancer is an aggressive disease
and that the treatment options available are limited. However, the
difficult job they have to do is to balance the additional therapeutic
benefit offered by these new treatments against their cost. The
assessment of the evidence shows that neither of these drugs
represents a good use of NHS resources." Read the press release at
http://www.nice.org.uk/page.aspx?o=401251

Hello all

I know this probably isn't the right place to be asking these
questions but I really didn't know where else to turn. I have a
firend, who I suspect is a compulsive liar and he is saying that he
has cancer of the large intestine. Now I worked in the cancer
services department for a year a couple of years ago so am fairly
clued up on treatment types but I have never heard of the treatments
that he is coming out with. He claims that he had cancer 7 years ago
when he was 14 and had a course of radiotherapy and that they didn't
get it all and now the cancerous cells have returned. His treatment
now is a daily injection of 10% or more of Barium into the stomach
(or leg as he's told some other people)now to me, this sound very
odd, barium is used for diagnostic tests, not treatment and If I type
it into google you don't get anything back! He also says that he's
having radiotherapy every few weeks at home (he claimed to be having
it at 2am one morning when a drunken friend tried to call him - i
think this was a guilt tactic!) but from the research that I've done -
radiotherapy (apart from not being a mainstream treatment for colon
cancer - correct me if I'm wrong) needs to be done far more often
than once every 3 weeks and certainly not "overnight" as it's a very
short procedure.

I'm aware that this is probably very inappropriate and if you feel
that it is then please tell me and I do apologise but I'm really
worried about my friend and just want some truthful answers.

Thank you for your help

Kelly

To a conventional physician, the tumor is the enemy.
Cancer is viewed as a local disease, namely the tumor. By cutting out
the tumor, irradiating it, or flooding the body with toxic (and often
carcinogenic) drugs, the conventional physician hopes to destroy the
tumor and restore the patient to health.
But all too often, the cancer is still present and has metastasized,
or re-occurs.
In contrast, the alternative physician regards cancer as one that
involves the whole body.
The tumor is merely a symptom and the cancer treatment aims to
correct the root causes of disease in the whole body.
Dr. Josef Issels, who successfully treated many ¡°incurable¡± cancer
patients, stated:
.. those who believe cancer is a local disease [that is, conventional
physicians] think that the tumor comes first and only afterwards
follows the generalised illness; those who think it is a generalised
disease of the body [alternative physicians] believe that first comes
the illness, and only afterwards the tumor¡­ from this basically
different way of looking at cancer, [the two types of physicians]
take separate paths towards the solution to cancer.
Cancer is a general disease of the whole body from the outset.
The tumor is a symptom of that illness.
It is my contention, based on twenty-five years of clinical
experience with over eight thousand cancer patients, that only by
recognising the disease is, and always has been, one affecting the
whole body from the outset, can it be more effectively arrested. By
adopting that principle, the statistics of survival can be improved
from the present grim position where eight out of every ten patients
die having received all possible surgery, radiotherapy and
chemotherapy.¡±
http://cancertreatmentqi.blogspot.com/#

Hi, I am Samuel Lau from Singapore. I just want to relay the message
that I seem to have stumbled upon a Chigong Teacher (in Malaysia) who
has had remarkable successes with treating over 1,000 cancer patients.
Most of them terminal and given up by conventional methods. I just wish
that the ¡®right¡¯ persons in need would get to know of this.

For details:

http://qigonghealingtreatment.com/YuYang_Testimonials.htm



[Non-text portions of this message have been removed]

Expert Interview
Colorectal Cancer -- Moving Biologics Into the Adjuvant Setting: An
Expert Interview With Dr. John Marshall
Posted 10/25/2006


Editor's Note:

The biologic targeted agents bevacizumab and cetuximab are both
approved for the treatment of metastatic colorectal cancer (CRC). In
February 2004, bevacizumab, a monoclonal antibody directed against
vascular endothelial growth factor, became the first targeted
antiangiogenic agent to receive US Food and Drug Administration
approval for the treatment of cancer. The indication for bevacizumab
has recently been expanded from refractory disease to include first-
line treatment of metastatic colorectal cancer. Cetuximab, a
monoclonal antibody directed against the epidermal growth factor
receptor (EGFR), is also approved for the treatment of patients with
metastatic CRC who have progressed on irinotecan or for those unable
to tolerate treatment with irinotecan. Several clinical trials are
now underway to evaluate these agents in the adjuvant setting. Emma
Hitt, PhD, recently spoke with John Marshall, MD, Director of
Developmental Therapeutics and Gastrointestinal Oncology, at the
Lombardi Comprehensive Cancer Center at Georgetown University, in
Washington, DC, on behalf of Medscape to discuss the current status
of clinical trials evaluating biologics for the adjuvant treatment of
colorectal cancer. Dr. Marshall described some of the practical
implications and remaining unanswered questions regarding the use of
these agents in early stage disease.

Medscape: What is the rationale for using bevacizumab and other
biologics as part of adjuvant treatment for CRC?

Dr. Marshall: The current standard of care for the treatment of
patients with stage III CRC is 12 cycles of FOLFOX [5-fluorouracil (5-
FU), leucovorin, and oxaliplatin] chemotherapy for 6 months. Whether
or not to use that same chemotherapy to treat patients with stage II
disease is controversial, but many believe that these patients should
receive the same duration of FOLFOX chemotherapy.

We know that in the metastatic setting, the antiangiogenic agent
bevacizumab and the EGFR inhibitor cetuximab have significantly
improved outcomes. So the next question we need to ask is whether
these biologic agents, when added to FOLFOX in patients with stage II
or III disease, will further increase progression-free and overall
survival in the adjuvant setting.

You could imagine that an antiangiogenic agent such as bevacizumab
would be effective in the adjuvant setting. If microscopic metastatic
disease were present, bevacizumab could perhaps delay the onset of
disease progression and prevent development of angiogenesis,
necessary for tumor growth.

Medscape: One of the major trials evaluating bevacizumab in the
adjuvant setting is the National Surgical Adjuvant Breast and Bowel
Project (NSABP) C-08 trial[1] --what is the rationale for that trial
and its current status?

The NSABP C-08 trial randomized patients with stage II or III disease
to receive mFOLFOX-6 for 12 cycles with or without bevacizumab.
Patients assigned to bevacizumab plus chemotherapy also received an
additional 6 months of bevacizumab alone. The premise for treating
patients with an additional 6 months of bevacizumab is that this
might further improve the progression-free survival. However, the
addition of 6 months of single-agent bevacizumab is pretty
controversial. At least in the metastatic setting, there are no data
to suggest that single-agent bevacizumab will have activity, so what
additional benefit it might provide when given alone for a further 6
months is unclear. In addition, the drug is not without side effects
(eg, bowel perforation, stroke, heart attack, and bleeding). Although
rare, these risks have to be weighed against the benefits.

Nonetheless, the NSABP C-08 trial is a very important study, the
results of which could immediately change the standard of care. The
trial has already completed accrual, and we will have results from
the trial in about 2 to 3 years.

Medscape: Can you describe the AVANT trial,[2] which is also
evaluating adjuvant bevacizumab?

Dr. Marshall: The AVANT trial, also conducted in patients with stage
II or III colorectal cancer, started out as a 3-arm clinical trial
and has a very similar design to that of the NSABP C-08 trial.
Patients received FOLFOX-4 chemotherapy alone, FOLFOX-4 plus
bevacizumab, or XELOX (capecitabine/oxaliplatin) plus bevacizumab.
This clinical trial was stopped at one point because of a higher rate
of sudden death due to cardiovascular events in the
capecitabine/oxaliplatin plus bevacizumab arm. Although the trial has
since been reopened, the accrual to that study has been actually
quite slow due to those concerns. I believe this trial will
eventually complete its accrual, but results will probably take
longer than for the NSABP C-08 trial.

Medscape: Are there any other late-phase trials of bevacizumab for
the adjuvant treatment of CRC?

Dr. Marshall: A randomized phase 3 trial[3] is also underway to study
combination chemotherapy with or without bevacizumab in patients who
have had surgery for stage II or III rectal cancer. In addition, a
phase 2 clinical trial, Eastern Cooperative Oncology Group (ECOG)
5202,[4] is identifying high-risk patients based on their genetic
profiles. This study is evaluating the feasibility of genetic
profiling using 2 genes: the DCC gene, also known as 18q loss of
heterozygosity, as well as the microsatellite instability (MSI) gene.

About 75% to 80% of patients with stage II disease will, in fact, be
cured by surgery, so if we treat, for example, 100 patients, we are
overtreating about 75 of those patients. Therefore, the goal of this
study is to determine whether we can identify the 25 or so patients
who may be at high risk and treat only those patients with
chemotherapy. Patients who are thought to be at low risk based on
their genetic profiles are not given chemotherapy and are simply
observed, whereas patients who have a high-risk genetic profile are
given FOLFOX-4 for 6 months or FOLFOX-4 for 6 months plus bevacizumab
for 12 months -- similar to the protocol used in the NSABP C-08
trial. This trial has only accrued a couple of hundred patients, but
it is a very selective study.

Medscape: Is bevacizumab often used off label in the adjuvant
setting, and what is your opinion about that?

Dr. Marshall: While I am fully supportive of the adjuvant clinical
trials with bevacizumab, and, frankly, I am hoping the results will
be positive, we have to remember that using bevacizumab off label in
the adjuvant setting is risky until adequate data are available. For
example, we were sure that irinotecan was going to work in the
adjuvant setting, but what we actually found was a significantly
increased toxicity rate in patients with early stage disease.

Bevacizumab has rare but significant acute toxicities associated with
its use. So, to risk using bevacizumab in the adjuvant setting for
the patient who will likely be cured with surgery is not appropriate
outside of the clinical trial. We know that there is a lot of usage
of bevacizumab outside of clinical trials, but it is going to take a
while to determine whether this drug actually is effective in the
adjuvant setting. I have not used adjuvant bevacizumab off label in
my practice.

Medscape: What about trials that are evaluating cetuximab and
panitumumab in the adjuvant setting?

Dr. Marshall: Basically, the rationale for using EGFR inhibitors in
the adjuvant setting would be similar to that for using bevacizumab.
These drugs have demonstrated a benefit in the metastatic and/or
refractory setting, and they are both working their way to earlier
front-line metastatic disease. Trials with the EGFR monoclonal
antibody cetuximab are underway in the adjuvant setting.

An Intergroup study (NCCTG-N0147; ECOG-N0147)[5] is currently
accruing patients and will evaluate 3 different combination
chemotherapy regimens with or without cetuximab for 6 months. Now
that the NSABP C-08 trial is closed, this trial should accrue very
rapidly. Another trial led by European researchers, called the PETACC-
8 study, will also include patients with fully resected stage III
colorectal cancer and will evaluate FOLFOX-4 with or without
cetuximab.[6]

One problem with cetuximab, though, is that it is often associated
with rash, which, in the adjuvant setting, may be particularly
difficult for patients to tolerate. So we are going to have to wait
to see what benefit may be observed with cetuximab in adjuvant
clinical trials, and how it may be balanced against the side effects.

Another monoclonal antibody directed against EGFR, panitumumab,
currently is not undergoing testing in the adjuvant setting, but
studies are being planned.

Medscape: Do you think there will be a role for single-agent use of
EGFR blockade in the adjuvant setting?

Dr. Marshall: EGFR blockade has shown single-agent activity.[7] The
proportion of responses is low, but some patients will respond to the
treatment. However, none of the studies so far is evaluating EGFR
blockade by itself -- as maintenance therapy, if you will -- in the
stage II or stage III setting. Currently, these agents are all being
evaluated with chemotherapy.

Medscape: What are some of the remaining unanswered questions about
the use of biologics in earlier-stage disease?

Dr. Marshall: One of the unanswered questions is how long to
administer adjuvant therapy. Currently we use 6 months of treatment,
but it would be useful to determine whether 4 months of therapy would
be equally effective. We have not asked that question on a large
scale in CRC. One small British study,[8] for example, found that 3
months of 5-FU was just as effective as 6 months of therapy, and we
have never really followed up on this issue. From a cost and side-
effect perspective, if 3 months of chemotherapy were as good as 6
months, this would obviously benefit patients and payers alike. So
this is a question that we ultimately need to ask with biologics in
the adjuvant setting as well.

We also need to establish how to individualize treatment. The E5202
study[4] is asking this question in high-risk patients with stage II
disease, but many patients are still being overtreated -- even those
with stage III disease. Therefore, as new technology becomes
available, it will be important to use arrays and genetic profiling
to determine who should receive chemotherapy and who should not.

Thus, establishing duration of therapy and identifying patients who
will benefit the most, I think, are the 2 biggest questions we are
trying to answer when considering using these agents in the adjuvant
setting.

References
Fluorouracil, Leucovorin, and Oxaliplatin With or Without Bevacizumab
in Treating Patients Who Have Undergone Surgery for Stage II or Stage
III Colon Cancer. Available at:
http://www.clinicaltrials.gov/ct/show/NCT00096278?order=1. Accessed
October 18, 2006.
Combination Chemotherapy With or Without Bevacizumab in Treating
Patients Who Have Undergone Surgery for Stage II or Stage III Colon
Cancer. Available at:
http://www.clinicaltrials.gov/ct/gui/show/NCT00112918. Accessed
October 18, 2006.
Combination Chemotherapy With or Without Bevacizumab in Treating
Patients Who Have Had Surgery for Stage II or Stage III Rectal
Cancer. Available at:
http://www.clinicaltrials.gov/ct/show/NCT00303628. Accessed October
18, 2006.
Oxaliplatin, Leucovorin, and Fluorouracil With or Without Bevacizumab
in Treating Patients Who Have Undergone Surgery for Stage II Colon
Cancer. Available at:
http://www.clinicaltrials.gov/ct/gui/show/NCT00217737. Accessed
October 18, 2006.
Comparison of Combination Chemotherapy Regimens With or Without
Cetuximab in Treating Patients Who Have Undergone Surgery for Stage
III Colon. Available at:
http://clinicaltrials.gov/ct/show/NCT00079274. Accessed October 18,
2006.
Combination Chemotherapy With or Without Cetuximab in Treating
Patients With Stage III Colon Cancer That Was Completely Removed by
Surgery. Available at:
http://www.clinicaltrials.gov/ct/show/NCT00265811. Accessed October
18, 2006.
Cunningham D, Humblet Y, Siena S, et al. Cetuximab monotherapy and
cetuximab plus irinotecan in irinotecan-refractory metastatic
colorectal cancer. N Engl J Med. 2004;351:337-345. Abstract
Chau I, Norman AR, Cunningham D, et al. A randomised comparison
between 6 months of bolus fluorouracil/leucovorin and 12 weeks of
protracted venous infusion fluorouracil as adjuvant treatment in
colorectal cancer. Ann Oncol. 2005;16:549-557. Abstract


Related Links
Resource Centers
Colorectal Cancer


Biologic Therapies in Cancer


Funding Information

Supported by an independent educational grant from Genentech




Interviewee affiliation: John Marshall, MD, Associate Professor of
Medicine; Chief, Hematology and Oncology, Georgetown University,
Washington, DC


Disclosure: Emma Hitt, PhD, has disclosed no relevant financial
relationships.

Disclosure: John Marshall, MD, has disclosed that he has received
grants for educational activities from, served as an advisor or
consultant to, and served on the speaker's bureaus of Roche, Sanofi,
Bristol-Myers Squibb, Genentech, and Pfizer.


Medscape Hematology-Oncology.  2006;9(2) ©2006 Medscape

From Medscape Hematology-Oncology

Expert Interview
Improving Chemotherapy for Patients With Colorectal Cancer: An Expert
Interview With Dr. Mace Rothenberg
Posted 08/24/2006


Editor's Note:
Therapeutic options for patients with colorectal cancer, and
particularly for those with advanced disease, have expanded
substantially over the last 5 years. Although no new classes of
agents emerged in 2006, many investigators are focusing on improving
the efficacy and reducing the toxicities of current combination
regimens. In the adjuvant setting, researchers are attempting to
apply recent molecular findings to identify individuals for whom the
benefits of toxic chemotherapy are likely to outweigh the risks.
Following the 2006 annual meeting of the American Society of Clinical
Oncology (ASCO), Margie Miller, Editorial Director of Medscape
Hematology-Oncology, asked Mace Rothenberg, MD, Professor of Medicine
(Hematology/Oncology) and Ingram Professor of Cancer Research at
Vanderbilt-Ingram Cancer Center in Nashville, Tennessee, to provide
his perspectives on how recently presented findings might influence
patient care.

Medscape: What would you consider the highlights of this year's ASCO
meeting, with respect to treatment of colorectal cancer?

Dr. Rothenberg: OPTIMOX 2,[1] which was a follow up to OPTIMOX 1,[2]
looked at the question of giving patients who have responded to
chemotherapy and are stable a chemotherapy-free period. OPTIMOX 1
evaluated the feasibility of an oxaliplatin-free interval -- not a
chemotherapy-free period -- and found that patients who were treated
with this "stop-and-go" approach for oxaliplatin fared every bit as
well, in terms of overall survival, as those individuals on FOLFOX
[oxaliplatin/5-fluorouracil (5-FU)/leucovorin] who did not have an
oxaliplatin-free interval. So, OPTIMOX 2 took this question to the
next level and asked whether we can give a patient a chemotherapy-
free period. FOLFOX7 was given for 6 cycles to patients in both arms,
but then patients in the experimental arm, instead of continuing on 5-
FU/leucovorin maintenance (as in OPTIMOX 1), received no maintenance
until progression, when chemotherapy with FOLFOX7 was reintroduced.

The duration of disease control, which was defined as the time from
first response until the point at which the tumor became larger than
it had been at baseline, was equivalent in both arms. In OPTIMOX 1,
the duration of disease control was 12.9 months and in OPTIMOX 2, it
was 11.7 months; the median chemotherapy-free interval in OPTIMOX 2
was 4.5 months. So this trial demonstrates that the duration of
disease control is equivalent whether you continue to administer some
chemotherapy or stop all chemotherapy until the tumor progresses.

This is, in fact, what many of us have begun to do; that is, when
patients achieve maximum response and there's no further tumor
shrinkage, we offer time off treatment. With these data, as well as
prior information indicating that overall outcomes are not
compromised, we can feel more comfortable giving patients time off
treatment, allowing them to resolve toxicities, to have time spent
out of the hospital, out of the clinic, traveling, on vacation,
allowing their normal tissue time to recover. It is very much
appreciated by patients, and that's the bottom line.

The follow up to this study, the DREAM trial being conducted in
Europe, will evaluate maintenance therapy, not with chemotherapy, but
with targeted drugs, such as bevacizumab or cetuximab, alone.

The next important study was by Labianca and colleagues,[3] in which
they looked at intermittent vs continuous FOLFIRI [irinotecan/5-
FU/leucovorin] in patients with advanced colorectal cancer. The
question was whether the irinotecan-based FOLFIRI regimen could be
stopped and restarted in a similar way and with similar outcomes to
the experience with the oxaliplatin-based FOLFOX regimen. FOLFIRI was
administered as first-line treatment to patients with metastatic
colorectal cancer for a short 2-month period. If the patient had a
response, treatment was stopped for 2 months, and then after a 2-
month break, the FOLFIRI was restarted. Patients were randomized
either to this "stop-and-go" approach or to continuous FOLFIRI.
Response rates were a bit lower than what we have come to expect from
first-line chemotherapy, probably because neither of these treatment
arms included either bevacizumab or cetuximab. Progression-free
survival in both arms was nearly identical at about 6.5 months, and
overall survival was identical at 17.5 months in both arms. So, this
study demonstrated that even with irinotecan-based first-line
therapy, you can treat for a short period of time -- just 2 months --
and thereafter begin to introduce some treatment-free intervals.

I think 2 months is a bit short from an American perspective because
we like to continue chemotherapy for as long as we see continuing
tumor shrinkage. We only consider stopping once that response
stabilizes.

I think these studies are important because they give us some comfort
with regard to changing a practice that we had long worried about.
Many of us were trained to continue to give chemotherapy to patients
whose disease has stabilized because we thought it might be valuable
in suppressing the tumor. We worried that as soon as the chemotherapy
was stopped, the tumor would come roaring back. Now we know that that
is not the case.

Fuchs and colleagues presented the results of the BICC-C study,[4] a
phase 3 trial initially designed to look at irinotecan in combination
with 3 methods of administering fluoropyridines: bolus 5-FU 2 weeks
out of 3 (modified IFL); bolus + infusional 5-FU every 2 weeks
(FOLFIRI regimen); and daily capecitabine for 14 out of every 21 days
(CAPEIRI). There was subsequently a second randomization to celecoxib
vs placebo in an attempt to improve efficacy.

The original trial design for 1000 patients had to be modified after
about a year of accrual to incorporate the recently approved
angiogenesis inhibitor bevacizumab. The capecitabine arm (CAPEIRI)
was discontinued, and it became just a 2-arm study: FOLFIRI plus
bevacizumab vs modified IFL [bolus 5-FU and leucovorin] plus
bevacizumab, followed by a second randomization to celecoxib vs
placebo.

When the investigators looked at the first part of the study, the
progression-free survival for FOLFIRI was superior to that achieved
with either modified IFL or CAPEIRI, and when they corrected for
other prognostic factors, there continued to be a significant
advantage for FOLFIRI compared with the other 2 arms. Although
differences in overall survival did not reach statistical
significance, the trend once again was for FOLFIRI to be superior to
the other 2 arms. Overall, toxicities were similar, with a slight
decrease in the rate of febrile neutropenia in patients in the
FOLFIRI arm and a higher rate of hand-foot syndrome in those treated
with CAPEIRI. Of note, the incidence of myocardial infarctions or
acute vascular events including heart attack, stroke, and 60-day
mortality rates was slightly higher for the IFL regimen than for
either of the 2 other arms.

There were only very preliminary data for the second phase of the
study, which looked at the 2 treatment arms, both of which included
bevacizumab. It was very underpowered, but it seems that although
progression-free survival was similar, overall survival was trending
in favor of the FOLFIRI regimen compared with modified IFL. Median
survival was 18.7 months for patients treated on the modified IFL
plus bevacizumab arm compared with a median survival that had not
been reached for the FOLFIRI plus bevacizumab arm. The death hazard
ratio for modified IFL was 2.5 compared with FOLFIRI plus bevacizumab
(P = .01). Even with a very small sample size, infusional 5-FU seems
to have advantages over bolus administration when given in
conjunction with irinotecan.

These researchers concluded that first-line FOLFIRI was more
effective than the other 2 treatment arms in part 1 of this study, in
terms of progression-free survival and toxicity, with a trend towards
improved overall survival as well. In period 2, first-line FOLFIRI
plus bevacizumab was associated with significantly longer survival
than modified IFL. Finally, celecoxib neither improved efficacy nor
reduced chemotherapy-related toxicity. Even though this was a trial
that never reached its primary accrual goal and had to be modified on
a couple of occasions, it generated important data regarding FOLFIRI
as the preferred way of administering combination chemotherapy with
irinotecan in the first-line setting and provided additional evidence
against the use of modified IFL.

Another large and important study by Cassidy and colleagues[5]
examined the question of whether a compound known as xaliproden could
reduce the cumulative peripheral sensory neuropathy associated with
oxaliplatin. More than 600 patients who were to receive FOLFOX4 first-
line for metastatic colorectal cancer were randomized to also receive
either xaliproden orally 1 mg/day or a placebo. The primary end
points were reduction of the risk of grade 3/4 cumulative sensory
neuropathy and noninferiority in response rate. The concern about
response centers around whether something that protects against
toxicity also protects the tumor against the antitumor effects of
chemotherapy. Results showed that there was about a 40% reduction in
the risk of developing grade 3 neuropathy in those individuals who
received xaliproden. These findings were statistically significant.

The time to recovery in those who had developed neuropathy was the
same for both arms, so the key was a delay in the onset and a lower
rate of grade 3 peripheral neuropathy. The objective response rates
(43% to 45%) and survival (19 months) were virtually identical in the
2 arms. Adverse events that might be attributed to xaliproden were
not seen, so this seems to be a fairly safe drug with few significant
toxicities. The conclusion was that xaliproden is a potentially
useful drug in delaying the onset and reducing the severity of the
cumulative peripheral neuropathy associated with oxaliplatin.

I think that the implications of this study have to be assessed in
the context of some of the observations made with the "stop-and-go"
approaches we've just described. If you are treating a patient in the
metastatic setting and you are able to achieve a maximal response
very early [with OPTIMOX 2, it was only 3 months] -- which is well
before most patients will develop grade 3 peripheral neuropathy --
the role of a protective agent such as xaliproden may be somewhat
diminished. In the Cassidy study, patients were given FOLFOX4
continuously, which is why they had the rates of peripheral
neuropathy that were observed.

Howard Hochster presented results from the TREE-2 study,[6] which
built on the experience in TREE-1 in 2 ways. First, it added
bevacizumab to all 3 treatment arms [modified FOLFOX;
capecitabine/oxaliplatin (CAPEOX); bolus 5-FU/oxaliplatin/leucovorin
(bFOL)]. Second, it used a reduced dose of capecitabine because of
the high rate of toxicities seen in the CAPEOX arm of TREE-1. In TREE-
2, the overall response rate was about 50% in the FOLFOX plus
bevacizumab and CAPEOX plus bevacizumab arms and closer to 40% in the
bFOL plus bevacizumab arm. The time to tumor progression and overall
survival were similar in the CAPEOX and FOLFOX arms (10 months and 26
months, respectively) but were somewhat less for those who had
received the bFOL regimen (8 months and 20 months, respectively).

The investigators concluded that oxaliplatin plus bevacizumab, with
either infusional 5-FU or capecitabine, appeared to be active in this
setting, with an acceptable toxicity profile. They also noted that
the activity of bFOL plus bevacizumab was not sufficiently
encouraging to be pursued further. I think it was important to show
that the tolerability of the capecitabine regimen could be improved
by reducing the dose and that the therapeutic outcomes for CAPEOX
plus bevacizumab were quite similar to FOLFOX plus bevacizumab.
Results from a phase 3 trial comparing these 2 regimens head-to-head
are expected within the next 6 months.

Alan Venook presented the results of CALGB 80203, a phase 3 study[7]
of FOLFIRI or FOLFOX that added cetuximab or placebo as first-line
therapy and asked a very important question. Patients were first
randomized to either FOLFOX or FOLFIRI, and then to either cetuximab
or placebo. The study was originally designed to accrue 2200 patients
with metastatic colorectal cancer but was closed by the Data and
Safety Monitoring Board after enrolling only 238 patients, primarily
because of the approval of bevacizumab in this setting. It was felt
that patients who were eligible should be receiving bevacizumab as
part of front-line therapy.

The primary end point of the study was to determine whether the
overall survival for patients with EGFR-expressing tumors treated
with cetuximab would be better than the survival in patients treated
with chemotherapy alone. Although the low accrual and short median
follow-up of the study prevented definitive conclusions from being
drawn at the time of the presentation, data on response rates and
progression-free survival were somewhat inconsistent. While the
addition of cetuximab to first-line chemotherapy appeared to improve
response rate -- 52% in those who received cetuximab vs 38% in those
who did not -- this difference did not carry over to progression-free
survival, where those who received chemotherapy plus cetuximab had a
median progression-free survival of 8.5 months and those who received
chemotherapy alone had a median progression-free survival of 9.4
months. It is possible that the impact of cetuximab may vary with the
specific chemotherapy regimen. For instance, the response rates were
about 40% for the FOLFIRI alone, FOLFIRI/cetuximab, and FOLFOX-alone
arms, but approximately 60% for the FOLFOX plus cetuximab arm.
However, the number of patients enrolled in this trial fell far short
of its goal, and any conclusions regarding comparative efficacy have
to be considered tentative, at best.

This study has now been replaced by an ongoing intergroup trial,
C80405, that is randomizing patients who receive either FOLFOX or
FOLFIRI to cetuximab, bevacizumab, or the combination. It is planned
to include more than 2200 patients.

Medscape: Moving from the metastatic setting to the adjuvant setting,
how should clinicians identify those patients with high-risk stage II
disease who are most likely to benefit from adjuvant therapy?

Dr. Rothenberg: Pooled analyses of stage II patients yield
conflicting results. According to the NSABP, for instance, the
magnitude of the impact of chemotherapy in the adjuvant setting is
around 30%, regardless of whether the patient has stage II or stage
III disease. I believe that this is correct. Unfortunately, because
the survival of patients with stage II disease is so much better than
for those with stage III, trials have failed to show a statistically
significant advantage for stage II patients. The question boils down
to: can we justify giving all patients chemotherapy when we know that
the majority of those with stage II disease are not destined to recur?

A trial that would randomize unselected patients with stage II
disease to chemotherapy vs no chemotherapy would require many
thousands of subjects. Moreover, although FOLFOX turns out to be a
more effective adjuvant regimen than 5-FU/leucovorin,[8,9] the use of
oxaliplatin introduces a toxicity, mainly neuropathy, that may be
long lasting and possibly permanent in some patients.

In an attempt to address these issues, an ongoing trial, E5202,[10]
is randomizing patients with locally advanced colon cancer to
chemotherapy or no chemotherapy on the basis of molecular
characterizations -- microsatellite instability and 18q loss of
heterozygosity -- that, in retrospective analyses, were associated
with poor prognosis.[11] Those considered to be "low risk" are
assigned to observation (ie, no chemotherapy). Those deemed to
be "high risk" are randomized to either FOLFOX alone or FOLFOX plus
bevacizumab. This trial opened in August 2005 and has accrued 121 of
a planned 3600 patients.

Ideally, we would randomize all stage II patients to either
chemotherapy or no chemotherapy, but the feeling was that it was
unethical to withhold treatment from those in whom bad outcome is
predicted. The study question is slightly different, therefore, in
that we will discover whether high-risk patients benefit from the
addition of bevacizumab.

Molecular characterization has finally emerged as a means of
selecting and assigning patients to treatment, and we are at least
taking a small step forward in determining what might be the best
approach for patients with stage II colon cancer.

Medscape: Looking ahead 12 to 18 months, what do you think are likely
to be the next significant therapeutic advances in colorectal cancer?

Dr. Rothenberg: We can't expect to see the same pace of progress in
advanced colorectal cancer that we've seen over the past 5 years. We
have been very fortunate to have a number of new drugs demonstrate
significant benefits in this disease, leading to a doubling of the
overall survival compared with 10 years ago. However, current trials
are really focused on refining those available treatments, learning
about ways to reduce toxicity, reduce cost, increase patient
acceptance, and increase tolerability. We want to determine whether
we can combine these drugs in an acceptable fashion.

A small randomized trial looked at first-line treatment with all
active cytotoxic agents together (FOLFOXIRI)[12] vs FOLFIRI, and the
response rates -- 66% for FOLFOXIRI, 41% for FOLFIRI -- were
significantly different. The percentage of patients who could
subsequently undergo potentially curative resections, 15% for the
FOLFOXIRI, 6% for FOLFIRI, were again significantly different.
Progression-free survival was improved for FOLFOXIRI compared with
FOLFIRI (9.8 months vs 6.9 months), and overall survival also favored
FOLFOXIRI -- 22.6 months vs 16.7 months. This small trial
demonstrated for the first time that combining all 3 active
chemotherapy drugs may be associated with certain advantages in terms
of efficacy. Not surprisingly, though, the rate of some toxicities
such as grade 3/4 neutropenia (50%) and febrile neutropenia, was also
increased. The incidence of grade 3/4 diarrhea was doubled, the
incidence of grade 3/4 vomiting was doubled, neurotoxicity was
higher -- this regimen was not without significant costs in terms of
patient toxicity. In today's world, where all eligible patients
receive biologicals as well as chemotherapy, one has to think about
the implications of these ever-expanding regimens.

For instance, if we added bevacizumab to FOLFOXIRI, would we achieve
further improvements? If so, would there be even greater efficacy by
combining FOLFOXIRI with bevacizumab plus cetuximab? In the past, we
knew that in most solid tumors, once we got much beyond 2 or 3
cytotoxic drugs, we reached the point of diminishing returns. Four
drugs are not better 3, and in many diseases, 3 are not better than
2. Nevertheless, these rules may not apply to biologicals, and trials
are underway to address this question in colorectal cancer.

Medscape: Do you have any "take-home" messages for practitioners
about treating patients with colorectal cancer?

Dr. Rothenberg: I think that we have to keep in mind that the
toxicities of these regimens are not trivial and that we have to
carefully monitor patients for diarrhea and neutropenia, especially
when they occur together. For patients with grade 3 neuropathy
associated with oxaliplatin or any vascular event associated with
bevacizumab, that agent should be stopped or switched. Patients on
capecitabine require close monitoring to make sure that the dose is
interrupted or adjusted at the earliest signs of hand-foot syndrome
or diarrhea. In fact, a poster was presented at this meeting by
Haller and colleagues[13] about the increased toxicity of
fluoropyridines, either capecitabine or 5-FU/leucovorin, in American
patients compared with patients in Europe or the Far East. We have to
be careful about managing these patients with more active, but also
potentially more toxic, therapies.

References
Maindrault-Goebel F, Lledo G, Chibaudel B, et al. OPTIMOX2, a large
randomized phase II study of maintenance therapy or chemotherapy-free
intervals (CFI) after FOLFOX in patients with metastatic colorectal
cancer (MRC). AGERCOR study. Proc Am Soc Clin Oncol. 2006;24:147s.
Abstract 3504.
Tournigand C, Cervantes A, Figer A, et al. OPTIMOX1: a randomized
study of FOLFOX4 or FOLFOX7 with oxaliplatin in a stop and go fashion
in advanced colorectal cancer -- a GERCOR study. J Clin Oncol.
2006;24:394-400. Abstract
Labianca R, Floriani I, Cortesi E, et al. Alternating versus
continuous "FOLFIRI" in advanced colorectal cancer (ACC): a
randomized "GISCAD" trial. Proc Am Soc Clin Oncol. 2006;24:147s.
Abstract 3505.
Fuchs C, Marshall J, Mitchell E, et al. A randomized trial of first-
line irinotecan/fluoropyrimidine combinations with or without
celecoxib in metastatic colorectal cancer (BICC-C). Proc Am Soc Clin
Oncol. 2006;24:147s. Abstract 3506.
Cassidy J, Bjarnason GA, Hickish T, et al. Randomized double blind
(DB) placebo (Plcb) controlled phase III study assessing the efficacy
of xaliproden (X) in reducing the cumulative peripheral sensory
neuropathy (PSN) induced by the oxaliplatin (Ox) and 5-FU/LV
combination (FOLFOX4) in first-line treatment of patients (pts) with
metastatic colorectal cancer (MCRC). Proc Am Soc Clin Oncol.
2006;24:147s. Abstract 3507.
Hochster HS, Hart LL, Ramanathan RK, et al. Safety and efficacy of
oxaliplatin/fluoropyrimidine regimens with or without bevacizumab as
first-line treatment of metastatic colorectal cancer (mCRC): final
analysis of the TREE-Study. Proc Am Soc Clin Oncol. 2006;24:148s.
Abstract 3510.
Venook A, Niedzwiecki D, Hollis D, et al. Phase III study of
irinotecan/5FU/LV (FOLFIRI) or oxaliplatin/5FU/LV (FOLFOX){±}
cetuximab for patients (pts) with untreated metastatic adenocarcinoma
of the colon or rectum (MCRC): CALGB 80203 preliminary results. Proc
Am Soc Clin Oncol. 2006;24:148s. Abstract 3509.
Andre T, Boni C, Mounedji-Boudiaf L, et al. Oxaliplatin, fluorouracil
and leucovorin as adjuvant treatment for colon cancer. N Engl J Med.
2004;350:2343-2351. Abstract
De Gramont A, Boni C, Navarro M, et al. Oxaliplatin/5FU/LV in the
adjuvant treatment of stage II and stage III colon cancer. Efficacy
results with a median follow-up of 4 years. Proc Am Soc Clin Oncol.
2005;23:246s. Abstract 3501.
Benson AB. Present and future role of prognostic and predictive
markers for patients with colorectal cancer. ASCO 2006 Educational
Book, pp 187-190.
Watanabe T, Wu TT, Catalano PJ, et al. Molecular predictors of
survival after adjuvant chemotherapy for colon cancer. N Engl J Med.
2001;344:1196-1206. Abstract
Falcone A, Masi G, Murr R, et al. Biweekly irinotecan, oxaliplatin,
and infusional 5FU/LV (FOLFOXIRI) versus FOLFIRI as first-line
treatment of metastatic colorectal cancer (MCRC): Results of a
randomized, phase III trial by the Gruppo Oncologico Nord Ovest
(GONO). Program and abstracts of the 2006 Gastrointestinal Cancers
Symposium; January 26-28, 2006; San Francisco, California. Abstract
199.
Haller DG, Cassidy J, Clarke S, et al. Tolerability of
fluoropyrimidines appears to differ by region. Proc Am Soc Clin
Oncol. 2006;24:149s. Abstract 3514.


Related Links
Resource Centers
Colorectal Cancer


Funding Information

Supported by an independent educational grant from sanofi-aventis.




Mace Rothenberg, MD, Professor of Medicine, Vanderbilt University
Medical School, Nashville, Tennessee; Attending Physician, Vanderbilt
University Medical Center, Nashville, Tennessee


Disclosure: Margie Miller has disclosed no relevant financial
relationships.

Disclosure: Mace Rothenberg, MD, has disclosed that he has received
grants for clinical research from and has served as an adviser or
consultant to Pfizer, sanofi-aventis, Roche, and ImClone. Dr.
Rothenberg has also disclosed that he has received grants for
educational activities from Pfizer and that he has served as an
advisor or consultant to Genentech.


Medscape Hematology-Oncology.  2006;9(2) ©2006 Medscape

MoA sounds very similar to the vascular targeting
agents in the clinic right now in that it targets the
core areas of solid tumors and leaves a viable tumor
rim supported by normal blood vasculature.

As this is preclin, I would from an investment pov.
rather go for e.g. OXGN that are already in phase
II/III clinical trials with combretastatin exploiting
exactly the same combination therapy tactic.

JMHO.

--- waveresearchlab <waveresearchlab@...> skrev:

> you have to check out the abstracts that are listed.
>  go to pubmed and
> read them, let us know what you think.
>
> --- In
> experimentalandunconventional@yahoogroups.com, Lars
> Tong
> Stromberg <kokostrollet@...> wrote:
> >
> > sounds promising in what way. Doesn´t say nada
> about
> > any results..
> >
> > --- waveresearchlab <waveresearchlab@...> skrev:
> >
> > > Study of Clostridium Novyi-NT Spores in Solid
> Tumors
> > > Malignancies
> > >
> >
>
http://www.clinicaltrials.gov/ct/show/NCT00358397?order=3
> > >
> > > This study is currently recruiting patients.
> > > Verified by Sidney Kimmel Comprehensive Cancer
> > > Center July 2006
> > > Sponsored by:  Sidney Kimmel Comprehensive
> Cancer
> > > Center
> > > Information provided by:  Sidney Kimmel
> > > Comprehensive Cancer Center
> > > ClinicalTrials.gov Identifier:  NCT00358397
> > >
> > > Purpose
> > > One time IV infusion of Clostridium novyi-NT
> spores
> > > to treat solid
> > > tumors which have not responded to standard
> therapy.
> > > Condition  Intervention  Phase
> > > Solid Tumors
> > > 	 Drug: Costridium novyi-NT spores
> > >  Phase I
> > >
> > > MedlinePlus consumer health information
> > >
> > > Study Type: Interventional
> > > Study Design: Treatment, Non-Randomized, Open
> Label,
> > > Uncontrolled,
> > > Single Group Assignment, Safety/Efficacy Study
> > >
> > > Official Title: Phase I Safety Study of
> Clostridium
> > > Novyi-NT Spores in
> > > Patients With Treatment-Refractory Solid Tumor
> > > Malignancies
> > > Further study details as provided by Sidney
> Kimmel
> > > Comprehensive
> > > Cancer Center:
> > > Primary Outcomes: To determine the safety
> profile,
> > > dose limiting
> > > toxicities (DLT), and maximum tolerated dose
> (MTD)
> > > of C. novyi–NT in
> > > humans with treatment-refractory solid tumor
> > > malignancies when given
> > > as a single intravenous injection.
> > > Secondary Outcomes: To document preliminary
> evidence
> > > of anti-tumor
> > > activity of C. novyi-NT in humans with
> > > treatment-refractory solid
> > > tumor malignancies when given as a single
> > > intravenous injection.; To
> > > analyze the pharmacokinetics of C. novyi-NT
> after
> > > administration to
> > > humans with treatment-refractory solid tumor
> > > malignancies when given
> > > as a single intravenous injection.; To measure
> the
> > > host immune and
> > > inflammatory response to C. novyi-NT in humans
> with
> > > treatment-refractory solid tumor malignancies
> when
> > > given as a single
> > > intravenous injection.
> > > Expected Total Enrollment:  20
> > >
> > > Study start: July 2006;  Expected completion:
> July
> > > 2008
> > > Last follow-up: July 2006;  Data entry closure:
> July
> > > 2006
> > > This is a phase I dose escalation study using a
> > > single dose of
> > > Clostridium novyi-NT spores in patients with
> > > treatment-refractory
> > > solid tumor malignancies. The overall objective
> of
> > > this study is to
> > > determine the safety and document any
> preliminary
> > > evidence of
> > > anti-tumor activity in this patient population.
> > >
> > > Eligibility
> > > Ages Eligible for Study:  18 Years and above,
> > > Genders Eligible for
> > > Study:  Both
> > > Criteria
> > >
> > > Inclusion Criteria:
> > >
> > >    1. Documented solid tumor malignancy as
> proven by
> > > referral CT scan
> > > of the chest, abdomen and pelvis.
> > >    2. Referral CT scan that demonstrates a
> necrotic
> > > core in primary
> > > target measuring at least 1 cm in diameter.
> > >    3. Patients must be refractory to standard
> > > chemotherapy or for whom
> > > no standard treatment exists. At least four
> weeks
> > > must have elapsed
> > > since completion of any prior chemotherapy.
> > >    4. Patients must have measurable disease;
> defined
> > > as at least one
> > > lesion whose longest diameter can be accurately
> > > measured as >2 cm.
> > >    5. ECOG performance status of 0 or 1.
> > >    6. Prior locoregional therapy, including
> > > cryotherapy,
> > > radiofrequency ablation, or regional
> chemotherapy is
> > > allowed if at
> > > least 6 weeks have elapsed.
> > >    7. Prior radiation therapy is allowed. At
> least 6
> > > weeks must have
> > > elapsed since the completion of radiation
> therapy
> > > and the patient must
> > > have recovered from side effects.
> > >    8. Prior systemic radionuclide therapy is
> > > allowed. At least 4 weeks
> > > must have elapsed since completion of the
> therapy.
> > >    9. Prior surgery is allowed. At least 6 weeks
> > > must have elapsed
> > > since the completion of major surgery and the
> > > patient must be fully
> > > recovered from this surgery and any attendant
> > > post-surgical complications.
> > >   10. Patients must be 18 years of age or older
> > >   11. Patients of childbearing potential must
> use
> > > adequate birth
> > > control measures
> > >   12. Negative serum pregnancy test for females
> of
> > > childbearing potential.
> > >
> > > Exclusion Criteria:
> > >
> > >    1. Weight < 135 kg
> > >    2. Chronic renal failure requiring
> hemodialysis
> > > or peritoneal dialysis
> > >    3. Tumor lesion that is not accessible to
> > > percutaneous drainage.
> > >    4. Any single contiguous lesion greater than
> >
> > > 12.5 cm.
> > >    5. The sum of the largest cross-sectional
> > > diameters from any number
> > > of non-contiguous lesions > 2 cm cannot be > 25
> cm.
> > >    6. Use of any investigational drug within 30
> days
> > > prior to
> > > screening or within 5 half-lives of the agent,
> > > whichever is longer.
> > >    7. Any documented evidence of primary brain
> > > malignancy or brain
> > > metastases
> > >    8. Patients with any clinically significant
> > > ascites or
> > > portosystemic hypertension, chronic jaundice or
> > > cirrhosis.
> > >    9. Patients with indwelling intrahepatic
> arterial
> > > pumps
> > >   10. Patients with prosthetic joints,
> prosthetic
> > > valves, pacemakers
> > > or any other implanted foreign materials.
> > >   11. Patients with any clinically significant
> > > pleural effusions
> > >   12. Patients with any evidence of hemodynamic
> > > compromise from a
> > > pericardial effusion.
> > >   13. Documented cirrhosis of the liver by
> clinical
> > > scenarios
> > > encompassing radiographic, clinical and
> laboratory
> > > results
> > >   14. Ongoing treatment with any
> immunosuppressive
> > > agent(s)
> > >   15. Any evidence of serious infections or
> history
> > > of chronic or
> > > recurrent infectious disease in the previous 3
> > > months.
> > >   16. Patients with opportunistic infections
> > >   17. Documented HIV infection.
> > >   18. Active or chronic Hepatitis B or Hepatitis
> C.
> > >   19. Presence of a transplanted solid organ.
> > >   20. History of an autoimmune disorder
> > >   21. History of Diabetes Mellitus (type I or
> II)
> > >   22. History of rheumatic fever, endocarditis,
> or
> > > greater than mild
> > > valvular disease.
> > >   23. Patients who depend upon COX II inhibitors
> or
> > > NSAIDS
> > >   24. History of ongoing and active arterial
> > > vasculopathy or evidence
> > > of end organ damage.
> > >   25. History of an ischemic insult in the
> previous
> > > 12 months
> > >   26. History of venous or lymphatic stasis
> > > resulting in venous stasis
> > > ulcers or greater than 2+ edema or lymphedema.
> > >   27. History of a splenectomy
> > >   28. Patients with a documented Penicillin or
> > > Metronidazole allergy
> > >   29. Patients with a documented allergy to
> > > radiology contrast dye.
> > >   30. Patient with active diverticulitis
> > >   31. Patient with active dental abscesses
> > >   32. Patients with inflammatory bowel disease
> > >   33. Patients with angiosarcoma
> > >   34. Patients with history of a positive PPD,
> past
> > > TB infection or
> > > past atypical mycobacterium infection.
> > >
> > > Location and Contact Information
> > > Please refer to this study by ClinicalTrials.gov
> > > identifier  NCT00358397
> > >
> > > Luis A Diaz, MD      443-287-6539    ldiaz1@...
> > >
> > > Maryland
> > >       Johns Hopkins Medical Institutes,
> Baltimore,
> > > Maryland,  21231,
> > >  United States; Recruiting
> > > Luis A Diaz, MD,  Principal Investigator
> > > Katherine Thornton, MD,  Sub-Investigator
> > > Bert Vogelstein, M.D.,  Sub-Investigator
> > > Ross Donehower, M.D.,  Sub-Investigator
> > > Michael Choti, M.D.,  Sub-Investigator
> > > Kenneth Kinzler, Ph.D.,  Sub-Investigator
> > >
> > > Study chairs or principal investigators
> > >
> > > Luis A Diaz, MD,  Principal Investigator,  Johns
> > > Hopkins Medicine
> > >
> > > More Information
> > >
> > > Publications
> > >
> > > Diaz LA Jr, Cheong I, Foss CA, Zhang X, Peters
> BA,
> > > Agrawal N,
> > > Bettegowda C, Karim B, Liu G, Khan K, Huang X,
> Kohli
> > > M, Dang LH, Hwang
> > > P, Vogelstein A, Garrett-Mayer E, Kobrin B,
> Pomper
> > > M, Zhou S, Kinzler
> > > KW, Vogelstein B, Huso DL. Pharmacologic and
> > > toxicologic evaluation of
> > > C. novyi-NT spores. Toxicol Sci. 2005
> > > Dec;88(2):562-75. Epub 2005 Sep 14.
> > >
> > > Folkman J. A novel anti-vascular therapy for
> cancer.
> > > Cancer Biol Ther.
> > > 2004 Mar;3(3):338-9. Epub 2004 Mar 29. No
> abstract
> > > available.
> > >
> > > Dang LH, Bettegowda C, Agrawal N, Cheong I, Huso
> D,
> > > Frost P, Loganzo
> > > F, Greenberger L, Barkoczy J, Pettit GR, Smith
> AB
> > > 3rd, Gurulingappa H,
> > > Khan S, Parmigiani G, Kinzler KW, Zhou S,
> Vogelstein
> > > B. Targeting
> > > vascular and avascular compartments of tumors
> with
> > > C. novyi-NT and
> > > anti-microtubule agents. Cancer Biol Ther. 2004
> > > Mar;3(3):326-37. Epub
> > > 2004 Mar 12.
> > >
> >
>
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=pubmed
> > >
> > > Bettegowda C, Dang LH, Abrams R, Huso DL,
> Dillehay
> > > L, Cheong I,
> > > Agrawal N, Borzillary S, McCaffery JM, Watson
> EL,
> > > Lin KS, Bunz F,
> > > Baidoo K, Pomper MG, Kinzler KW, Vogelstein B,
> Zhou
> > > S. Overcoming the
> > > hypoxic barrier to radiation therapy with
> anaerobic
> > > bacteria. Proc
> > > Natl Acad Sci U S A. 2003 Dec 9;100(25):15083-8.
> > > Epub 2003 Dec 1.
> > >
> > > Dang LH, Bettegowda C, Huso DL, Kinzler KW,
> > > Vogelstein B. Combination
> > > bacteriolytic therapy for the treatment of
> > > experimental tumors. Proc
> > > Natl Acad Sci U S A. 2001 Dec
> 18;98(26):15155-60.
> > > Epub 2001 Nov 27.
> > >
> > > Agrawal N, Bettegowda C, Cheong I, Geschwind JF,
> > > Drake CG, Hipkiss EL,
> > > Tatsumi M, Dang LH, Diaz LA Jr, Pomper M,
> Abusedera
> > > M, Wahl RL,
> > > Kinzler KW, Zhou S, Huso DL, Vogelstein B.
> > > Bacteriolytic therapy can
> > > generate a potent immune response against
> > > experimental tumors. Proc
> > > Natl Acad Sci U S A. 2004 Oct
> 19;101(42):15172-7.
> > > Epub 2004 Oct 7.
> > >
> > > Jain RK, Forbes NS. Can engineered bacteria help
> > > control cancer? Proc
> > > Natl Acad Sci U S A. 2001 Dec
> 18;98(26):14748-50. No
> > > abstract available.
> > >
> > >
> > >
> > >
> > >
> > >
> > > Yahoo! Groups Links
> > >
> > >
> >
>
http://groups.yahoo.com/group/experimentalandunconventional/
> > >
> > >
> > >
> >
>
experimentalandunconventional-unsubscribe@yahoogroups.com
> > >
> > >
> > >
> > >
> > >
> >
>
>
>
>
>
>
>
> Yahoo! Groups Links
>
>
http://groups.yahoo.com/group/experimentalandunconventional/
>
>
>
experimentalandunconventional-unsubscribe@yahoogroups.com
>
>
>
>
>

you have to check out the abstracts that are listed.  go to pubmed and
read them, let us know what you think.

--- In experimentalandunconventional@yahoogroups.com, Lars Tong
Stromberg <kokostrollet@...> wrote:
>
> sounds promising in what way. Doesn´t say nada about
> any results..
>
> --- waveresearchlab <waveresearchlab@...> skrev:
>
> > Study of Clostridium Novyi-NT Spores in Solid Tumors
> > Malignancies
> >
> http://www.clinicaltrials.gov/ct/show/NCT00358397?order=3
> >
> > This study is currently recruiting patients.
> > Verified by Sidney Kimmel Comprehensive Cancer
> > Center July 2006
> > Sponsored by:  Sidney Kimmel Comprehensive Cancer
> > Center
> > Information provided by:  Sidney Kimmel
> > Comprehensive Cancer Center
> > ClinicalTrials.gov Identifier:  NCT00358397
> >
> > Purpose
> > One time IV infusion of Clostridium novyi-NT spores
> > to treat solid
> > tumors which have not responded to standard therapy.
> > Condition  Intervention  Phase
> > Solid Tumors
> > 	 Drug: Costridium novyi-NT spores
> >  Phase I
> >
> > MedlinePlus consumer health information
> >
> > Study Type: Interventional
> > Study Design: Treatment, Non-Randomized, Open Label,
> > Uncontrolled,
> > Single Group Assignment, Safety/Efficacy Study
> >
> > Official Title: Phase I Safety Study of Clostridium
> > Novyi-NT Spores in
> > Patients With Treatment-Refractory Solid Tumor
> > Malignancies
> > Further study details as provided by Sidney Kimmel
> > Comprehensive
> > Cancer Center:
> > Primary Outcomes: To determine the safety profile,
> > dose limiting
> > toxicities (DLT), and maximum tolerated dose (MTD)
> > of C. novyi–NT in
> > humans with treatment-refractory solid tumor
> > malignancies when given
> > as a single intravenous injection.
> > Secondary Outcomes: To document preliminary evidence
> > of anti-tumor
> > activity of C. novyi-NT in humans with
> > treatment-refractory solid
> > tumor malignancies when given as a single
> > intravenous injection.; To
> > analyze the pharmacokinetics of C. novyi-NT after
> > administration to
> > humans with treatment-refractory solid tumor
> > malignancies when given
> > as a single intravenous injection.; To measure the
> > host immune and
> > inflammatory response to C. novyi-NT in humans with
> > treatment-refractory solid tumor malignancies when
> > given as a single
> > intravenous injection.
> > Expected Total Enrollment:  20
> >
> > Study start: July 2006;  Expected completion: July
> > 2008
> > Last follow-up: July 2006;  Data entry closure: July
> > 2006
> > This is a phase I dose escalation study using a
> > single dose of
> > Clostridium novyi-NT spores in patients with
> > treatment-refractory
> > solid tumor malignancies. The overall objective of
> > this study is to
> > determine the safety and document any preliminary
> > evidence of
> > anti-tumor activity in this patient population.
> >
> > Eligibility
> > Ages Eligible for Study:  18 Years and above,
> > Genders Eligible for
> > Study:  Both
> > Criteria
> >
> > Inclusion Criteria:
> >
> >    1. Documented solid tumor malignancy as proven by
> > referral CT scan
> > of the chest, abdomen and pelvis.
> >    2. Referral CT scan that demonstrates a necrotic
> > core in primary
> > target measuring at least 1 cm in diameter.
> >    3. Patients must be refractory to standard
> > chemotherapy or for whom
> > no standard treatment exists. At least four weeks
> > must have elapsed
> > since completion of any prior chemotherapy.
> >    4. Patients must have measurable disease; defined
> > as at least one
> > lesion whose longest diameter can be accurately
> > measured as >2 cm.
> >    5. ECOG performance status of 0 or 1.
> >    6. Prior locoregional therapy, including
> > cryotherapy,
> > radiofrequency ablation, or regional chemotherapy is
> > allowed if at
> > least 6 weeks have elapsed.
> >    7. Prior radiation therapy is allowed. At least 6
> > weeks must have
> > elapsed since the completion of radiation therapy
> > and the patient must
> > have recovered from side effects.
> >    8. Prior systemic radionuclide therapy is
> > allowed. At least 4 weeks
> > must have elapsed since completion of the therapy.
> >    9. Prior surgery is allowed. At least 6 weeks
> > must have elapsed
> > since the completion of major surgery and the
> > patient must be fully
> > recovered from this surgery and any attendant
> > post-surgical complications.
> >   10. Patients must be 18 years of age or older
> >   11. Patients of childbearing potential must use
> > adequate birth
> > control measures
> >   12. Negative serum pregnancy test for females of
> > childbearing potential.
> >
> > Exclusion Criteria:
> >
> >    1. Weight < 135 kg
> >    2. Chronic renal failure requiring hemodialysis
> > or peritoneal dialysis
> >    3. Tumor lesion that is not accessible to
> > percutaneous drainage.
> >    4. Any single contiguous lesion greater than >
> > 12.5 cm.
> >    5. The sum of the largest cross-sectional
> > diameters from any number
> > of non-contiguous lesions > 2 cm cannot be > 25 cm.
> >    6. Use of any investigational drug within 30 days
> > prior to
> > screening or within 5 half-lives of the agent,
> > whichever is longer.
> >    7. Any documented evidence of primary brain
> > malignancy or brain
> > metastases
> >    8. Patients with any clinically significant
> > ascites or
> > portosystemic hypertension, chronic jaundice or
> > cirrhosis.
> >    9. Patients with indwelling intrahepatic arterial
> > pumps
> >   10. Patients with prosthetic joints, prosthetic
> > valves, pacemakers
> > or any other implanted foreign materials.
> >   11. Patients with any clinically significant
> > pleural effusions
> >   12. Patients with any evidence of hemodynamic
> > compromise from a
> > pericardial effusion.
> >   13. Documented cirrhosis of the liver by clinical
> > scenarios
> > encompassing radiographic, clinical and laboratory
> > results
> >   14. Ongoing treatment with any immunosuppressive
> > agent(s)
> >   15. Any evidence of serious infections or history
> > of chronic or
> > recurrent infectious disease in the previous 3
> > months.
> >   16. Patients with opportunistic infections
> >   17. Documented HIV infection.
> >   18. Active or chronic Hepatitis B or Hepatitis C.
> >   19. Presence of a transplanted solid organ.
> >   20. History of an autoimmune disorder
> >   21. History of Diabetes Mellitus (type I or II)
> >   22. History of rheumatic fever, endocarditis, or
> > greater than mild
> > valvular disease.
> >   23. Patients who depend upon COX II inhibitors or
> > NSAIDS
> >   24. History of ongoing and active arterial
> > vasculopathy or evidence
> > of end organ damage.
> >   25. History of an ischemic insult in the previous
> > 12 months
> >   26. History of venous or lymphatic stasis
> > resulting in venous stasis
> > ulcers or greater than 2+ edema or lymphedema.
> >   27. History of a splenectomy
> >   28. Patients with a documented Penicillin or
> > Metronidazole allergy
> >   29. Patients with a documented allergy to
> > radiology contrast dye.
> >   30. Patient with active diverticulitis
> >   31. Patient with active dental abscesses
> >   32. Patients with inflammatory bowel disease
> >   33. Patients with angiosarcoma
> >   34. Patients with history of a positive PPD, past
> > TB infection or
> > past atypical mycobacterium infection.
> >
> > Location and Contact Information
> > Please refer to this study by ClinicalTrials.gov
> > identifier  NCT00358397
> >
> > Luis A Diaz, MD      443-287-6539    ldiaz1@...
> >
> > Maryland
> >       Johns Hopkins Medical Institutes, Baltimore,
> > Maryland,  21231,
> >  United States; Recruiting
> > Luis A Diaz, MD,  Principal Investigator
> > Katherine Thornton, MD,  Sub-Investigator
> > Bert Vogelstein, M.D.,  Sub-Investigator
> > Ross Donehower, M.D.,  Sub-Investigator
> > Michael Choti, M.D.,  Sub-Investigator
> > Kenneth Kinzler, Ph.D.,  Sub-Investigator
> >
> > Study chairs or principal investigators
> >
> > Luis A Diaz, MD,  Principal Investigator,  Johns
> > Hopkins Medicine
> >
> > More Information
> >
> > Publications
> >
> > Diaz LA Jr, Cheong I, Foss CA, Zhang X, Peters BA,
> > Agrawal N,
> > Bettegowda C, Karim B, Liu G, Khan K, Huang X, Kohli
> > M, Dang LH, Hwang
> > P, Vogelstein A, Garrett-Mayer E, Kobrin B, Pomper
> > M, Zhou S, Kinzler
> > KW, Vogelstein B, Huso DL. Pharmacologic and
> > toxicologic evaluation of
> > C. novyi-NT spores. Toxicol Sci. 2005
> > Dec;88(2):562-75. Epub 2005 Sep 14.
> >
> > Folkman J. A novel anti-vascular therapy for cancer.
> > Cancer Biol Ther.
> > 2004 Mar;3(3):338-9. Epub 2004 Mar 29. No abstract
> > available.
> >
> > Dang LH, Bettegowda C, Agrawal N, Cheong I, Huso D,
> > Frost P, Loganzo
> > F, Greenberger L, Barkoczy J, Pettit GR, Smith AB
> > 3rd, Gurulingappa H,
> > Khan S, Parmigiani G, Kinzler KW, Zhou S, Vogelstein
> > B. Targeting
> > vascular and avascular compartments of tumors with
> > C. novyi-NT and
> > anti-microtubule agents. Cancer Biol Ther. 2004
> > Mar;3(3):326-37. Epub
> > 2004 Mar 12.
> >
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=pubmed
> >
> > Bettegowda C, Dang LH, Abrams R, Huso DL, Dillehay
> > L, Cheong I,
> > Agrawal N, Borzillary S, McCaffery JM, Watson EL,
> > Lin KS, Bunz F,
> > Baidoo K, Pomper MG, Kinzler KW, Vogelstein B, Zhou
> > S. Overcoming the
> > hypoxic barrier to radiation therapy with anaerobic
> > bacteria. Proc
> > Natl Acad Sci U S A. 2003 Dec 9;100(25):15083-8.
> > Epub 2003 Dec 1.
> >
> > Dang LH, Bettegowda C, Huso DL, Kinzler KW,
> > Vogelstein B. Combination
> > bacteriolytic therapy for the treatment of
> > experimental tumors. Proc
> > Natl Acad Sci U S A. 2001 Dec 18;98(26):15155-60.
> > Epub 2001 Nov 27.
> >
> > Agrawal N, Bettegowda C, Cheong I, Geschwind JF,
> > Drake CG, Hipkiss EL,
> > Tatsumi M, Dang LH, Diaz LA Jr, Pomper M, Abusedera
> > M, Wahl RL,
> > Kinzler KW, Zhou S, Huso DL, Vogelstein B.
> > Bacteriolytic therapy can
> > generate a potent immune response against
> > experimental tumors. Proc
> > Natl Acad Sci U S A. 2004 Oct 19;101(42):15172-7.
> > Epub 2004 Oct 7.
> >
> > Jain RK, Forbes NS. Can engineered bacteria help
> > control cancer? Proc
> > Natl Acad Sci U S A. 2001 Dec 18;98(26):14748-50. No
> > abstract available.
> >
> >
> >
> >
> >
> >
> > Yahoo! Groups Links
> >
> >
> http://groups.yahoo.com/group/experimentalandunconventional/
> >
> >
> >
> experimentalandunconventional-unsubscribe@yahoogroups.com
> >
> >
> >
> >
> >
>

sounds promising in what way. Doesn´t say nada about
any results..

--- waveresearchlab <waveresearchlab@...> skrev:

> Study of Clostridium Novyi-NT Spores in Solid Tumors
> Malignancies
>
http://www.clinicaltrials.gov/ct/show/NCT00358397?order=3
>
> This study is currently recruiting patients.
> Verified by Sidney Kimmel Comprehensive Cancer
> Center July 2006
> Sponsored by:  Sidney Kimmel Comprehensive Cancer
> Center
> Information provided by:  Sidney Kimmel
> Comprehensive Cancer Center
> ClinicalTrials.gov Identifier:  NCT00358397
>
> Purpose
> One time IV infusion of Clostridium novyi-NT spores
> to treat solid
> tumors which have not responded to standard therapy.
> Condition  Intervention  Phase
> Solid Tumors
> 	 Drug: Costridium novyi-NT spores
>  Phase I
>
> MedlinePlus consumer health information
>
> Study Type: Interventional
> Study Design: Treatment, Non-Randomized, Open Label,
> Uncontrolled,
> Single Group Assignment, Safety/Efficacy Study
>
> Official Title: Phase I Safety Study of Clostridium
> Novyi-NT Spores in
> Patients With Treatment-Refractory Solid Tumor
> Malignancies
> Further study details as provided by Sidney Kimmel
> Comprehensive
> Cancer Center:
> Primary Outcomes: To determine the safety profile,
> dose limiting
> toxicities (DLT), and maximum tolerated dose (MTD)
> of C. novyi–NT in
> humans with treatment-refractory solid tumor
> malignancies when given
> as a single intravenous injection.
> Secondary Outcomes: To document preliminary evidence
> of anti-tumor
> activity of C. novyi-NT in humans with
> treatment-refractory solid
> tumor malignancies when given as a single
> intravenous injection.; To
> analyze the pharmacokinetics of C. novyi-NT after
> administration to
> humans with treatment-refractory solid tumor
> malignancies when given
> as a single intravenous injection.; To measure the
> host immune and
> inflammatory response to C. novyi-NT in humans with
> treatment-refractory solid tumor malignancies when
> given as a single
> intravenous injection.
> Expected Total Enrollment:  20
>
> Study start: July 2006;  Expected completion: July
> 2008
> Last follow-up: July 2006;  Data entry closure: July
> 2006
> This is a phase I dose escalation study using a
> single dose of
> Clostridium novyi-NT spores in patients with
> treatment-refractory
> solid tumor malignancies. The overall objective of
> this study is to
> determine the safety and document any preliminary
> evidence of
> anti-tumor activity in this patient population.
>
> Eligibility
> Ages Eligible for Study:  18 Years and above,
> Genders Eligible for
> Study:  Both
> Criteria
>
> Inclusion Criteria:
>
>    1. Documented solid tumor malignancy as proven by
> referral CT scan
> of the chest, abdomen and pelvis.
>    2. Referral CT scan that demonstrates a necrotic
> core in primary
> target measuring at least 1 cm in diameter.
>    3. Patients must be refractory to standard
> chemotherapy or for whom
> no standard treatment exists. At least four weeks
> must have elapsed
> since completion of any prior chemotherapy.
>    4. Patients must have measurable disease; defined
> as at least one
> lesion whose longest diameter can be accurately
> measured as >2 cm.
>    5. ECOG performance status of 0 or 1.
>    6. Prior locoregional therapy, including
> cryotherapy,
> radiofrequency ablation, or regional chemotherapy is
> allowed if at
> least 6 weeks have elapsed.
>    7. Prior radiation therapy is allowed. At least 6
> weeks must have
> elapsed since the completion of radiation therapy
> and the patient must
> have recovered from side effects.
>    8. Prior systemic radionuclide therapy is
> allowed. At least 4 weeks
> must have elapsed since completion of the therapy.
>    9. Prior surgery is allowed. At least 6 weeks
> must have elapsed
> since the completion of major surgery and the
> patient must be fully
> recovered from this surgery and any attendant
> post-surgical complications.
>   10. Patients must be 18 years of age or older
>   11. Patients of childbearing potential must use
> adequate birth
> control measures
>   12. Negative serum pregnancy test for females of
> childbearing potential.
>
> Exclusion Criteria:
>
>    1. Weight < 135 kg
>    2. Chronic renal failure requiring hemodialysis
> or peritoneal dialysis
>    3. Tumor lesion that is not accessible to
> percutaneous drainage.
>    4. Any single contiguous lesion greater than >
> 12.5 cm.
>    5. The sum of the largest cross-sectional
> diameters from any number
> of non-contiguous lesions > 2 cm cannot be > 25 cm.
>    6. Use of any investigational drug within 30 days
> prior to
> screening or within 5 half-lives of the agent,
> whichever is longer.
>    7. Any documented evidence of primary brain
> malignancy or brain
> metastases
>    8. Patients with any clinically significant
> ascites or
> portosystemic hypertension, chronic jaundice or
> cirrhosis.
>    9. Patients with indwelling intrahepatic arterial
> pumps
>   10. Patients with prosthetic joints, prosthetic
> valves, pacemakers
> or any other implanted foreign materials.
>   11. Patients with any clinically significant
> pleural effusions
>   12. Patients with any evidence of hemodynamic
> compromise from a
> pericardial effusion.
>   13. Documented cirrhosis of the liver by clinical
> scenarios
> encompassing radiographic, clinical and laboratory
> results
>   14. Ongoing treatment with any immunosuppressive
> agent(s)
>   15. Any evidence of serious infections or history
> of chronic or
> recurrent infectious disease in the previous 3
> months.
>   16. Patients with opportunistic infections
>   17. Documented HIV infection.
>   18. Active or chronic Hepatitis B or Hepatitis C.
>   19. Presence of a transplanted solid organ.
>   20. History of an autoimmune disorder
>   21. History of Diabetes Mellitus (type I or II)
>   22. History of rheumatic fever, endocarditis, or
> greater than mild
> valvular disease.
>   23. Patients who depend upon COX II inhibitors or
> NSAIDS
>   24. History of ongoing and active arterial
> vasculopathy or evidence
> of end organ damage.
>   25. History of an ischemic insult in the previous
> 12 months
>   26. History of venous or lymphatic stasis
> resulting in venous stasis
> ulcers or greater than 2+ edema or lymphedema.
>   27. History of a splenectomy
>   28. Patients with a documented Penicillin or
> Metronidazole allergy
>   29. Patients with a documented allergy to
> radiology contrast dye.
>   30. Patient with active diverticulitis
>   31. Patient with active dental abscesses
>   32. Patients with inflammatory bowel disease
>   33. Patients with angiosarcoma
>   34. Patients with history of a positive PPD, past
> TB infection or
> past atypical mycobacterium infection.
>
> Location and Contact Information
> Please refer to this study by ClinicalTrials.gov
> identifier  NCT00358397
>
> Luis A Diaz, MD      443-287-6539    ldiaz1@...
>
> Maryland
>       Johns Hopkins Medical Institutes, Baltimore,
> Maryland,  21231,
>  United States; Recruiting
> Luis A Diaz, MD,  Principal Investigator
> Katherine Thornton, MD,  Sub-Investigator
> Bert Vogelstein, M.D.,  Sub-Investigator
> Ross Donehower, M.D.,  Sub-Investigator
> Michael Choti, M.D.,  Sub-Investigator
> Kenneth Kinzler, Ph.D.,  Sub-Investigator
>
> Study chairs or principal investigators
>
> Luis A Diaz, MD,  Principal Investigator,  Johns
> Hopkins Medicine
>
> More Information
>
> Publications
>
> Diaz LA Jr, Cheong I, Foss CA, Zhang X, Peters BA,
> Agrawal N,
> Bettegowda C, Karim B, Liu G, Khan K, Huang X, Kohli
> M, Dang LH, Hwang
> P, Vogelstein A, Garrett-Mayer E, Kobrin B, Pomper
> M, Zhou S, Kinzler
> KW, Vogelstein B, Huso DL. Pharmacologic and
> toxicologic evaluation of
> C. novyi-NT spores. Toxicol Sci. 2005
> Dec;88(2):562-75. Epub 2005 Sep 14.
>
> Folkman J. A novel anti-vascular therapy for cancer.
> Cancer Biol Ther.
> 2004 Mar;3(3):338-9. Epub 2004 Mar 29. No abstract
> available.
>
> Dang LH, Bettegowda C, Agrawal N, Cheong I, Huso D,
> Frost P, Loganzo
> F, Greenberger L, Barkoczy J, Pettit GR, Smith AB
> 3rd, Gurulingappa H,
> Khan S, Parmigiani G, Kinzler KW, Zhou S, Vogelstein
> B. Targeting
> vascular and avascular compartments of tumors with
> C. novyi-NT and
> anti-microtubule agents. Cancer Biol Ther. 2004
> Mar;3(3):326-37. Epub
> 2004 Mar 12.
>
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=pubmed
>
> Bettegowda C, Dang LH, Abrams R, Huso DL, Dillehay
> L, Cheong I,
> Agrawal N, Borzillary S, McCaffery JM, Watson EL,
> Lin KS, Bunz F,
> Baidoo K, Pomper MG, Kinzler KW, Vogelstein B, Zhou
> S. Overcoming the
> hypoxic barrier to radiation therapy with anaerobic
> bacteria. Proc
> Natl Acad Sci U S A. 2003 Dec 9;100(25):15083-8.
> Epub 2003 Dec 1.
>
> Dang LH, Bettegowda C, Huso DL, Kinzler KW,
> Vogelstein B. Combination
> bacteriolytic therapy for the treatment of
> experimental tumors. Proc
> Natl Acad Sci U S A. 2001 Dec 18;98(26):15155-60.
> Epub 2001 Nov 27.
>
> Agrawal N, Bettegowda C, Cheong I, Geschwind JF,
> Drake CG, Hipkiss EL,
> Tatsumi M, Dang LH, Diaz LA Jr, Pomper M, Abusedera
> M, Wahl RL,
> Kinzler KW, Zhou S, Huso DL, Vogelstein B.
> Bacteriolytic therapy can
> generate a potent immune response against
> experimental tumors. Proc
> Natl Acad Sci U S A. 2004 Oct 19;101(42):15172-7.
> Epub 2004 Oct 7.
>
> Jain RK, Forbes NS. Can engineered bacteria help
> control cancer? Proc
> Natl Acad Sci U S A. 2001 Dec 18;98(26):14748-50. No
> abstract available.
>
>
>
>
>
>
> Yahoo! Groups Links
>
>
http://groups.yahoo.com/group/experimentalandunconventional/
>
>
>
experimentalandunconventional-unsubscribe@yahoogroups.com
>
>
>
>
>

Study of Clostridium Novyi-NT Spores in Solid Tumors Malignancies
http://www.clinicaltrials.gov/ct/show/NCT00358397?order=3

This study is currently recruiting patients.
Verified by Sidney Kimmel Comprehensive Cancer Center July 2006
Sponsored by:  Sidney Kimmel Comprehensive Cancer Center
Information provided by:  Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:  NCT00358397

Purpose
One time IV infusion of Clostridium novyi-NT spores to treat solid
tumors which have not responded to standard therapy.
Condition  Intervention  Phase
Solid Tumors
	  Drug: Costridium novyi-NT spores
	 Phase I

MedlinePlus consumer health information

Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled,
Single Group Assignment, Safety/Efficacy Study

Official Title: Phase I Safety Study of Clostridium Novyi-NT Spores in
Patients With Treatment-Refractory Solid Tumor Malignancies
Further study details as provided by Sidney Kimmel Comprehensive
Cancer Center:
Primary Outcomes: To determine the safety profile, dose limiting
toxicities (DLT), and maximum tolerated dose (MTD) of C. novyi–NT in
humans with treatment-refractory solid tumor malignancies when given
as a single intravenous injection.
Secondary Outcomes: To document preliminary evidence of anti-tumor
activity of C. novyi-NT in humans with treatment-refractory solid
tumor malignancies when given as a single intravenous injection.; To
analyze the pharmacokinetics of C. novyi-NT after administration to
humans with treatment-refractory solid tumor malignancies when given
as a single intravenous injection.; To measure the host immune and
inflammatory response to C. novyi-NT in humans with
treatment-refractory solid tumor malignancies when given as a single
intravenous injection.
Expected Total Enrollment:  20

Study start: July 2006;  Expected completion: July 2008
Last follow-up: July 2006;  Data entry closure: July 2006
This is a phase I dose escalation study using a single dose of
Clostridium novyi-NT spores in patients with treatment-refractory
solid tumor malignancies. The overall objective of this study is to
determine the safety and document any preliminary evidence of
anti-tumor activity in this patient population.

Eligibility
Ages Eligible for Study:  18 Years and above,  Genders Eligible for
Study:  Both
Criteria

Inclusion Criteria:

    1. Documented solid tumor malignancy as proven by referral CT scan
of the chest, abdomen and pelvis.
    2. Referral CT scan that demonstrates a necrotic core in primary
target measuring at least 1 cm in diameter.
    3. Patients must be refractory to standard chemotherapy or for whom
no standard treatment exists. At least four weeks must have elapsed
since completion of any prior chemotherapy.
    4. Patients must have measurable disease; defined as at least one
lesion whose longest diameter can be accurately measured as >2 cm.
    5. ECOG performance status of 0 or 1.
    6. Prior locoregional therapy, including cryotherapy,
radiofrequency ablation, or regional chemotherapy is allowed if at
least 6 weeks have elapsed.
    7. Prior radiation therapy is allowed. At least 6 weeks must have
elapsed since the completion of radiation therapy and the patient must
have recovered from side effects.
    8. Prior systemic radionuclide therapy is allowed. At least 4 weeks
must have elapsed since completion of the therapy.
    9. Prior surgery is allowed. At least 6 weeks must have elapsed
since the completion of major surgery and the patient must be fully
recovered from this surgery and any attendant post-surgical complications.
   10. Patients must be 18 years of age or older
   11. Patients of childbearing potential must use adequate birth
control measures
   12. Negative serum pregnancy test for females of childbearing potential.

Exclusion Criteria:

    1. Weight < 135 kg
    2. Chronic renal failure requiring hemodialysis or peritoneal dialysis
    3. Tumor lesion that is not accessible to percutaneous drainage.
    4. Any single contiguous lesion greater than > 12.5 cm.
    5. The sum of the largest cross-sectional diameters from any number
of non-contiguous lesions > 2 cm cannot be > 25 cm.
    6. Use of any investigational drug within 30 days prior to
screening or within 5 half-lives of the agent, whichever is longer.
    7. Any documented evidence of primary brain malignancy or brain
metastases
    8. Patients with any clinically significant ascites or
portosystemic hypertension, chronic jaundice or cirrhosis.
    9. Patients with indwelling intrahepatic arterial pumps
   10. Patients with prosthetic joints, prosthetic valves, pacemakers
or any other implanted foreign materials.
   11. Patients with any clinically significant pleural effusions
   12. Patients with any evidence of hemodynamic compromise from a
pericardial effusion.
   13. Documented cirrhosis of the liver by clinical scenarios
encompassing radiographic, clinical and laboratory results
   14. Ongoing treatment with any immunosuppressive agent(s)
   15. Any evidence of serious infections or history of chronic or
recurrent infectious disease in the previous 3 months.
   16. Patients with opportunistic infections
   17. Documented HIV infection.
   18. Active or chronic Hepatitis B or Hepatitis C.
   19. Presence of a transplanted solid organ.
   20. History of an autoimmune disorder
   21. History of Diabetes Mellitus (type I or II)
   22. History of rheumatic fever, endocarditis, or greater than mild
valvular disease.
   23. Patients who depend upon COX II inhibitors or NSAIDS
   24. History of ongoing and active arterial vasculopathy or evidence
of end organ damage.
   25. History of an ischemic insult in the previous 12 months
   26. History of venous or lymphatic stasis resulting in venous stasis
ulcers or greater than 2+ edema or lymphedema.
   27. History of a splenectomy
   28. Patients with a documented Penicillin or Metronidazole allergy
   29. Patients with a documented allergy to radiology contrast dye.
   30. Patient with active diverticulitis
   31. Patient with active dental abscesses
   32. Patients with inflammatory bowel disease
   33. Patients with angiosarcoma
   34. Patients with history of a positive PPD, past TB infection or
past atypical mycobacterium infection.

Location and Contact Information
Please refer to this study by ClinicalTrials.gov identifier  NCT00358397

Luis A Diaz, MD      443-287-6539    ldiaz1@...

Maryland
       Johns Hopkins Medical Institutes, Baltimore,  Maryland,  21231,
  United States; Recruiting
Luis A Diaz, MD,  Principal Investigator
Katherine Thornton, MD,  Sub-Investigator
Bert Vogelstein, M.D.,  Sub-Investigator
Ross Donehower, M.D.,  Sub-Investigator
Michael Choti, M.D.,  Sub-Investigator
Kenneth Kinzler, Ph.D.,  Sub-Investigator

Study chairs or principal investigators

Luis A Diaz, MD,  Principal Investigator,  Johns Hopkins Medicine

More Information

Publications

Diaz LA Jr, Cheong I, Foss CA, Zhang X, Peters BA, Agrawal N,
Bettegowda C, Karim B, Liu G, Khan K, Huang X, Kohli M, Dang LH, Hwang
P, Vogelstein A, Garrett-Mayer E, Kobrin B, Pomper M, Zhou S, Kinzler
KW, Vogelstein B, Huso DL. Pharmacologic and toxicologic evaluation of
C. novyi-NT spores. Toxicol Sci. 2005 Dec;88(2):562-75. Epub 2005 Sep 14.

Folkman J. A novel anti-vascular therapy for cancer. Cancer Biol Ther.
2004 Mar;3(3):338-9. Epub 2004 Mar 29. No abstract available.

Dang LH, Bettegowda C, Agrawal N, Cheong I, Huso D, Frost P, Loganzo
F, Greenberger L, Barkoczy J, Pettit GR, Smith AB 3rd, Gurulingappa H,
Khan S, Parmigiani G, Kinzler KW, Zhou S, Vogelstein B. Targeting
vascular and avascular compartments of tumors with C. novyi-NT and
anti-microtubule agents. Cancer Biol Ther. 2004 Mar;3(3):326-37. Epub
2004 Mar 12.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=pubmed

Bettegowda C, Dang LH, Abrams R, Huso DL, Dillehay L, Cheong I,
Agrawal N, Borzillary S, McCaffery JM, Watson EL, Lin KS, Bunz F,
Baidoo K, Pomper MG, Kinzler KW, Vogelstein B, Zhou S. Overcoming the
hypoxic barrier to radiation therapy with anaerobic bacteria. Proc
Natl Acad Sci U S A. 2003 Dec 9;100(25):15083-8. Epub 2003 Dec 1.

Dang LH, Bettegowda C, Huso DL, Kinzler KW, Vogelstein B. Combination
bacteriolytic therapy for the treatment of experimental tumors. Proc
Natl Acad Sci U S A. 2001 Dec 18;98(26):15155-60. Epub 2001 Nov 27.

Agrawal N, Bettegowda C, Cheong I, Geschwind JF, Drake CG, Hipkiss EL,
Tatsumi M, Dang LH, Diaz LA Jr, Pomper M, Abusedera M, Wahl RL,
Kinzler KW, Zhou S, Huso DL, Vogelstein B. Bacteriolytic therapy can
generate a potent immune response against experimental tumors. Proc
Natl Acad Sci U S A. 2004 Oct 19;101(42):15172-7. Epub 2004 Oct 7.

Jain RK, Forbes NS. Can engineered bacteria help control cancer? Proc
Natl Acad Sci U S A. 2001 Dec 18;98(26):14748-50. No abstract available.

From Medscape Hematology-Oncology

Expert Interview
Evolution of EGFR Inhibition for Metastatic Colon Cancer: An Expert
Interview With Dr. Neal Meropol
Posted 07/31/2006


Editor's Note:

Approximately 150,000 Americans are diagnosed with colorectal cancer
(CRC) each year, with half a million cases reported worldwide. After
several decades of incremental improvements in chemotherapy, 2 new
targeted monoclonal antibodies were approved by the US Food and Drug
Administration in February 2004 for treatment of patients with
metastatic colorectal cancer. Cetuximab, which targets the epidermal
growth factor receptor (EGFR), and bevacizumab, which targets the
vascular endothelial growth factor (VEGF) receptor, have been shown
to improve the outcome of patients with metastatic colorectal cancer.
At this juncture, researchers are eager to evaluate the potential
value of these targeted agents earlier in disease, and clinical
trials in the adjuvant setting are ongoing. The challenge moving
forward in the metastatic setting is to determine optimal sequencing
and combinations, as well as ways to identify patients for whom
treatment may be curative. At the 2006 annual meeting of the American
Society of Clinical Oncology, there were a number of studies
demonstrating some intriguing and promising early results. On behalf
of Medscape, Sally Church, PhD, interviewed Neal J. Meropol, MD,
Director of the Gastrointestinal Cancer Program and Director of the
Gastrointestinal Tumor Risk Assessment Program at Fox Chase Cancer
Center in Philadelphia to discuss how treatment regimens for patients
with metastatic CRC have evolved and to review newly reported data.

Medscape: We have heard much about the role of VEGF inhibition in
CRC, but what is the significance of blocking EGFR? Is there a role
for it in treating front-line CRC, in addition to its current use in
later lines of therapy?

Dr. Meropol: It has been known for decades that the EGFR is
associated with neoplastic transformation. Many different types of
human tumors express EGFR on the surfaces of cancer cells. Once this
discovery was made, a variety of experiments were conducted in the
laboratory, showing that interruption of signaling from these
receptors on the cell surface could result in either the death of
cancer cells -- apoptosis -- or a reduction in their proliferation.
Based on these preclinical findings, reagents were developed to try
to target the EGFR pathway in humans.

When signaling takes place through growth factor receptors, a cascade
of events brings a signal from the surface of the cell to the nucleus
that results, ultimately, in the production of proteins leading to
proliferation, metastatic potential, and a decrease in apoptosis --
all of which are hallmarks of cancer. So, the hope was that by
interrupting the signaling of growth factor receptors -- in this
case, EGFR -- these processes would be reduced, and the virulence of
cancer cells in humans would be attenuated. The first proof of
principle of this hypothesis is represented by cetuximab, a chimeric
monoclonal antibody directed against the EGFR. This antibody
interferes with the usual interaction of this receptor with its
ligand or ligands in the extracellular matrix and also perturbs the
signaling of the receptor.

Additionally, other reagents, which are not antibodies but are small
molecules that interact with the tyrosine kinase domain of the EGFR,
have also shown activity in human cancer, particularly in non-small-
cell lung cancer and pancreatic cancer. These drugs include gefitinib
and erlotinib. VEGF as a target has received a lot of press recently
because of the success of clinical trials using bevacizumab in a
variety of different types of cancer, but there is also a significant
buzz with regard to EGF blockade.

Medscape: What is the significance of potentially blocking VEGF and
EGFR simultaneously? Is this a feasible strategy? Might it be more
effective than blocking these targets individually?

Dr. Meropol: Cetuximab and panitumumab -- an investigational
monoclonal antibody against EGFR that is far along in clinical
development -- were both initially developed as second- or third-line
agents to be used after failure of initial chemotherapy. Cetuximab
was evaluated as a single agent as well as in combination with
irinotecan chemotherapy, initially. Notably, the response rate with
cetuximab in combination with irinotecan was twice as high as with
cetuximab by itself, which validated findings of preclinical
experiments. One of the most interesting observations from this study
was that this doubling of response rate occurred in patients who had
previously failed therapy with irinotecan, so somehow there is a
cooperation between cetuximab and irinotecan that overcomes
irinotecan resistance or perhaps, in some patients, overcomes
cetuximab resistance. After it became evident that both cetuximab and
panitumumab had activity in second- or third-line treatment of
metastatic colorectal cancer, there was a natural effort to try to
move them into earlier lines of treatment. These clinical trials
addressing the earlier use of the EGFR monoclonal antibodies in colon
cancer are currently ongoing. Of note, although the monoclonal
antibodies against EGFR have shown activity against CRC, the small-
molecule inhibitors of EGFR have not.

At this year's ASCO meeting, Alan Venook from UCSF described
preliminary results from a clinical trial[1] with EGFR inhibitors as
first-line treatment. Patients with previously untreated metastatic
CRC were given chemotherapy alone or chemotherapy in combination with
cetuximab. The choice of the chemotherapy was left up to the
discretion of the treating physician and could be FOLFOX or FOLFIRI.
The study was originally designed to include more than 1000 patients,
but because of changes in the CRC treatment landscape, notably the
introduction of bevacizumab into front-line therapy, the study was
discontinued because of poor accrual. Nevertheless, preliminary
results with approximately 60 patients in each of the 4 treatment
groups showed that those who received cetuximab in combination with
either oxaliplatin or irinotecan had a higher response rate than
those patients who did not receive cetuximab. At this point, the
impact of those higher response rates on overall survival or
progression-free survival cannot be determined because of the small
sample size. Furthermore, it is not clear at this time whether there
is greater cooperation of cetuximab with a particular chemotherapy
regimen, that is to say whether it works better with FOLFIRI or with
FOLFOX.

The study that Dr. Venook reported has been replaced by a new
intergroup study in which patients are randomly assigned to 1 of 3
treatment approaches as initial management of metastatic CRC. The
first is chemotherapy with cetuximab; the second is chemotherapy with
bevacizumab, which has now become standard; and the third arm is
chemotherapy with both cetuximab and bevacizumab. This study is
currently accruing patients. As in the previous study, the choice of
chemotherapy backbone (ie, FOLFOX or FOLFIRI) is left up to the
discretion of the treating physician.

The other new drug in development is panitumumab, which is not yet
approved by the FDA for marketing in the United States but has been
associated with an improvement in progression-free survival compared
with best supportive care in a European study of patients with
refractory CRC. An ongoing study in North America is comparing
chemotherapy plus bevacizumab vs chemotherapy with bevacizumab plus
panitumumab. One of the distinguishing features of panitumumab
compared with cetuximab is the structure of the antibody. Whereas
cetuximab is a chimeric monoclonal antibody (meaning that it has
about 30% of a mouse murine component to it), panitumumab is a fully
human antibody. For this reason, panitumumab appears to be associated
with a significantly lower chance of allergic reactions. At this
point, the comparative efficacy of these 2 antibodies is uncertain.

The concept of using both EGFR and VEGF inhibitors in colorectal
cancer is currently being explored. The reason that there is so much
interest in this type of combination is that it has been known for
some time that one of the downstream effects of EGFR stimulation is
an increase in production of VEGF. This led to the hypothesis that
blocking both ends of this sequence of events might produce a more
potent antitumor effect. There has been an early signal that this
might, in fact, be the case in a small randomized phase 2 study[2]
reported at the ASCO meeting in 2005 by Leonard Saltz. Patients who
had failed therapy with irinotecan but had never received bevacizumab
were randomly assigned to receive either cetuximab plus bevacizumab
or cetuximab, bevacizumab, and irinotecan. The 35% response rate in
the group of patients that received both antibodies with irinotecan
appeared to be in excess of what one would expect. In contrast, the
group that received bevacizumab plus cetuximab without irinotecan had
a response rate of about 20%. These were intriguing and provocative
results, but there were only about 40 patients in each arm, so it was
quite preliminary. The current ongoing front-line studies will
clearly define the role of dual blockade of EGFR and VEGF in
metastatic CRC.

Medscape: Were there any other presentations of interest with regard
to EGFR inhibition in metastatic CRC?

Dr. Meropol: Jose Baselga reported on a phase 1 study[3] combining 2
classes of EGFR inhibitors, that is to say a monoclonal antibody,
cetuximab, along with a tyrosine kinase inhibitor, gefitinib. This
phase 1 dose-finding study concluded that it was safe to administer
full doses of both drugs. One of the most provocative findings from
this study was that of 9 CRC patients who were treated with both
drugs, 5 experienced a partial response. This is a very small number
of patients in a very early study, so it is premature to conclude
that a response rate in excess of 50% should be expected with this
combination. Nevertheless, the data certainly support further
exploration of dual inhibition of the EGFR signaling pathway in
patients with CRC.

Other EGFR-related reports included 2 small studies from Randolph
Hecht[4] and Jordan Berlin[5] that looked at the use of an every-
other-week schedule of panitumumab administration. Cetuximab is
currently administered weekly, but because of the pharmacokinetic
properties of panitumumab, it may be possible to administer that
agent on an every-other-week schedule. In these 2 small preliminary
studies, a response rate of approximately 10% confirmed the activity
of panitumumab administered as a single agent on an every-other-week
schedule in patients who had previously received oxaliplatin,
irinotecan, and 5-fluorouracil for metastatic CRC.

Medscape: How do you see future regimens for patients with CRC
evolving?

Dr. Meropol: Right now, there are 2 major directions for research.
One is in refinement of new therapeutic approaches that have come to
the clinic in the past few years. The large studies going on in CRC
are geared toward helping us optimize use of the available agents.
Questions about the optimal use of therapy include not only whether
more is better, but also how to determine which patients are most
likely to benefit from a particular treatment so that we can better
match our treatments to individual patients. Also, a major focus is
the identification of those patients with metastatic CRC who are
potentially curable. Unlike most other solid tumors, metastatic CRC
is curable if the metastases are surgically resectable. Some patients
whose disease is not resectable at time of diagnosis can be treated
with effective systemic treatment, which shrinks the tumor to the
point where the patient can then undergo surgery with curative
intent. The challenge for us is to identify those patients who might
ultimately be surgically curable and provide them the greatest
opportunity for long-term survival by initiating the most aggressive
treatment available as their initial therapy. In essence, we are
learning how to stratify patients with metastatic CRC into 2 groups:
those for whom metastatic disease will be a chronic process with on-
again, off-again treatment over a course of years, and those who
might be cured with more intensive initial therapy followed by
surgical resection.

The second major ongoing research direction is a vigorous effort to
identify novel agents with new mechanisms of action that might be
added to our armamentarium against CRC. Inhibitors of other growth
factor receptor pathways, such as the insulin-like growth factor
receptor pathway, are being tested in a number of different tumor
types.[6,7] In addition, there are molecular targets that have not
been previously explored and are not affected by current treatments,
such as the TRAIL receptor pathway,[8] which is a proapoptotic
pathway. These new directions hold promise for additional benefit,
and trials to investigate safety and efficacy are underway.

References
Venook A, Niedzwiecki D, Hollis D, et al. Phase III study of
irinotecan/5FU/LV (FOLFIRI) or oxaliplatin/5FU/LV (FOLFOX) {±}
cetuximab for patients (pts) with untreated metastatic adenocarcinoma
of the colon or rectum (MCRC): CALGB 80203 preliminary results. Proc
Am Soc Clin Oncol. 2006;24:148s. Abstract 3509.
Saltz LB, Lenz HJ, Hochster H, et al. Randomized phase II trial of
cetuximab/bevacizumab/irinotecan (CBI) versus cetuximab/bevacizumab
(CB) in irinotecan-refractory colorectal cancer. Proc Am Soc Clin
Oncol. 2005;23:248s. Abstract 3508.
Baselga J, Schoffski P, Rojo F, et al. A phase I pharmacokinetic (PK)
and molecular pharmacodynamic (PD) study of the combination of two
anti-EGFR therapies, the monoclonal antibody (MAb) cetuximab (C) and
the tyrosine kinase inhibitor (TKI) gefitinib (G), in patients (pts)
with advanced colorectal (CRC), head and neck (HNC) and non-small
cell lung cancer (NSCLC). Proc Am Soc Clin Oncol. 2006;24:122s.
Abstract 3006.
Hecht J, Mitchell E, Baranda J, et al. Panitumumab antitumor activity
in patients (pts) with metastatic colorectal cancer (mCRC) expressing
low (1-9%) or negative (<1%) levels of epidermal growth factor
receptor (EGFr). Proc Am Soc Clin Oncol. 2006;24:157s. Abstract 3547.
Berlin J, Neubauer M, Swanson P, et al. Panitumumab antitumor
activity in patients (pts) with metastatic colorectal cancer (mCRC)
expressing &#8805; 10% epidermal growth factor receptor (EGFr). Proc Am Soc
Clin Oncol. 2006;24:158s. Abstract 3548.
Attard G, Fong PC, Molife R, et al. Phase I trial involving the
pharmacodynamic (PD) study of circulating tumour cells, of CP-751,871
(C), a monoclonal antibody against the insulin-like growth factor 1
receptor (IGF-1R), with docetaxel (D) in patients (p) with advanced
cancer. Proc Am Soc Clin Oncol. 2006;24:126s. Abstract 3023.
Morgillo F, Hong WK, Lee H. Insulin-like growth factor-1
receptor/epidermal growth factor receptor (EGFR) heterodimerization
and resistance to epidermal growth factor receptor tyrosine kinase
inhibitors in non-small-cell lung cancer. Proc Am Soc Clin Oncol.
2006;24:604s. Abstract 13032.
Herbst RS, Mendolson DS, Ebbinghaus S, et al. A phase I safety and
pharmacokinetic (PK) study of recombinant Apo2L/TRAIL, an apoptosis-
inducing protein in patients with advanced cancer. Proc Am Soc Clin
Oncol. 2006;24:124s. Abstract 3013.


Related Links
Resource Centers
Colorectal Cancer


Funding Information

Supported by an independent educational grant from Bristol-Myers
Squibb/Imclone.




Interviewee Affiliation: Neal J. Meropol, MD, Director,
Gastrointestinal Cancer Program, Fox Chase Cancer Center,
Philadelphia, Pennsylvania


Disclosure for Interviewer: Sally Church, PhD, has disclosed that she
has served as a consultant for sanofi-aventis and NeoRx.

Disclosure for Interviewee: Neal J. Meropol, MD, has disclosed that
he has received grants for clinical research from Bristol-Myers
Squibb and Pfizer. Dr. Meropol has also disclosed that he has served
as an advisor or consultant to Genentech, Bristol-Myers Squibb,
Amgen, and Pfizer.


Medscape Hematology-Oncology.  2006;9(2) ©2006 Medscape

Cancer information and help.

Possible information that may help you or someone you know.

http://wadesterscancerinfo.blogspot.com

An Open Letter and Petition
   From Americans
   Who Want Colon Cancer Stopped Now


   Send to:
   Colorectal Cancer Network
   PO box 182 Kensington MD 20895
   www.colorectal-cancer.net
   301-879-1500


   We the undersigned, Citizens, Voters, Families, Friends, Americans, having
endured the loss of 56,000 fellow Americans year upon year, decade after decade,
now demand that action be taken.   From the moment of the discovery that polyps
turn into colon cancer, and their removal prevents it, we had the ability to
nearly end this cancer 100%.

   We ask that you mandate that all insurance companies cover colonoscopies along
with other appropriate screening tools for everyone 18-20 and older.  56,000
lives will be lost this year, and every year until you do.  135,000+ Americans
will be diagnosed with colon cancer every year devastating their financial
resources and often tearing their families apart.


     PRINT NAME / ADDRESS / CITY / STATE / ZIP
     SIGNATURE
       1


       2


       3


       4


       5


       6


       7


       8


       9


       10


       11


       12


       13


       14


       15






   Instructions for Petition Volunteers:



   1) Make copies of this petition form before collecting signatures.



   2) Collect signatures.  We need name, Address, City, State, Zip.
     We will keep a running tally of the number and locations of signatures.
     When this reaches a critical number we will begin posting it on the
ProjectMARCH webpage:
     http://www.colorectal-cancer.net/projectmarch.htm




   DEADLINE!!   All petitions must be back by July 31, 2006.





















Narice May,
Project March PA State Coordinator
Erie, PA
END COLON CANCER!!
Colonoscpies for ALL PA Adults
Not just those over 50
pm_pastatecoordinator@...
__________________________________________________
Do You Yahoo!?
Tired of spam?  Yahoo! Mail has the best spam protection around
http://mail.yahoo.com

[Non-text portions of this message have been removed]



130-150,000 people will be diagnosed with colorectal cancer this
year. Many at stages 3 and 4.
The low end cost for treatment is $80,000/year. New treatments look
to push this figure well over $100,000.
Our goal is to gather 1000+ people touched by Colon Cancer before
age 50
We will meet In Washington DC and MARCH on Capital Hill on March 26
at 10 AM to demand screening for ALL ADULTS not just those over 50.

Because with a few more screenings
NO ONE would have to get this cancer
  Initial Colonoscopy for MEN & WOMEN  at age 18-21
     Colon Cancer doesn't wait for us to turn 50!!
Screen every 5 years or less FOR LIFE not stopping at 75. Prevention
shouldn't end because you reach a certain age!!

It's that simple It's that necessary!
No one should be dying of this cancer when prevention is this simple.
We CAN  END THIS CANCER! NOW!
BUT………………………
If you don't speak up Who WILL??
The END IS IN SIGHT BUT ONLY
IF WE  WILL STAND UP AND BE HEARD
To volunteer in Pennsylvania contact:  Narice May
                                     PA State Coordinator

pm_pastatecoordinator@...
National Coordinators
Priscilla Savary  psavary@...

                   Louise Bates  lbates@...

  Website:     http://health.groups.yahoo.com/group/ProjectMARCH/

Computer Industry Workers May Face Cancer Risks

   http://www.studyandjobs.com/Comp_worker_cancer.html

   or visit
   http://www.studyandjobs.com/Cancer.html

   Regards

   StudyAndJobs

__________________________________________________
Do You Yahoo!?
Tired of spam?  Yahoo! Mail has the best spam protection around
http://mail.yahoo.com

[Non-text portions of this message have been removed]

My name is Narice May and I am writing you to ask your consideration
of guidelines aimed at eliminating colon cancer by mandating
colonoscopy screening for all adults in the Commonwealth beginning
at age 18 NOT 50.

On December 5,2005 I lost my husband Phillip to colorectal cancer.
Phil was only 46. He NEVER was offered a colonoscopy despite the
fact his mother and grandmother died of Pancreatic and Uterine
cancer. These cancers are said to have some link to HEREDITARY colon
cancer. Even with this history Phil had no symptoms of cancer. He
was young, fit and appeared healthy so why would anyone even THINK
to test him?

    BUT the same could be said about my 32 year old friend Amy Carter
who died of
Breast Cancer and had no history. The difference is that today Amy
and her
daughter would be checked for BREAST & CERVICAL cancer regardless of
age. Why
don't we do the same for colon cancer?

    A colonoscopy can detect polyps and eradicate them BEFORE cancer
develops.
There is NO OTHER CANCER that has that claim. We have the ability to
PREVENT
and possibly totally ELIMINATE colon cancer and yet 50,000 plus
people will DIE
of this brutal disease this year.

    A Colonoscopy is paid for IF an adult is 50 and over but 50
didn't save my
husband. You see, a good number of individuals are 40, 30, yes even
20 something,
when they are diagnosed with stage 4 cancer. Most are inoperable at
that point
meaning there is no cure just treatment to prolong life.
Treatment that costs hundreds of thousands of tax and/or state
insurance dollars.
Pennsylvania is paying out far too much in survivor benefits,
welfare, Medicaid and Disability.

    Why? Because we have not demanded and mandated that we change the
guidelines
so that ALL adults can be tested every 3-5 years beginning at age
18. We spend
about 5-6,000 dollars every 3-5 years and we save taxpayers hundreds
of
thousands of dollars in lost wages, insurance, health care costs,
and priceless
loss of friends and family to this heartless killer.

Project March is a grassroots organization under the auspices of The
Colorectal  Cancer Network  an organization comprised of those whose
lives have been forever changed by this disease.
You can find their guidelines and suggestions at:

http://www.colorectal-cancer.net/projectmarch.htm

I urge you to read these guidelines and consider that the answer is
so very simple.
Screen everyone and no one should get colon cancer and the tiny
percent that is not caught can be easily treated.

Don't go with the flow on this one. You have the chance to be the
person or group who took the time to take a stand and make a
difference.
Those of you who work in Oncology, Surgery, and GI practices have
seen the devastation up close. Now's the time. Here is your chance
to make a difference!
Won't you please join me in ending Colon Cancer?

Thank you for your time and concern
Sincerely,






Narice May,
Project March PA State Coordinator
Erie, PA
END COLON CANCER!!
Colonoscpies for ALL PA Adults
Not just those over 50
pm_pastatecoordinator@...

---------------------------------------------------------------------
-----------