COXIB Potential for Slowing Cancer Progression
A few days before the Vioxx recall, Raj Pruthi, MD, FACS, assistant professor
of surgery, University of North Carolina, presented results of a small
one-year study of Celebrex at the annual Clinical Congress of the American
College of Surgeons. Pruthi said, "This is the first report of a Cox-2
inhibitor having a therapeutic effect in prostate cancer at any stage of the
disease." He had shown that in 22 out of 24 men with biochemical recurrence of
prostate cancer, 400 to 800 mg of Celebrex a day slowed the rise of prostate
specific antigen (PSA), which, following primary treatment, is a marker of
recurrent disease.

Pruthi's study of Celebrex ran for only 12 months (with Vioxx, cardiovascular
problems appeared in patients who took the drug for 18 months or more).

The National Cancer Institute (NCI) is running scores of small studies and
full scale clinical trials like Dr. Pruthi's. NCI is concerned about the
impact of the Vioxx recall on its research into this entire class of drugs,
including Celebrex. In order for these studies to go forward with confidence,
more, not less, openness and accountability will be required. Not just two
drugs but generations of even more promising knock-offs are at stake.

The FDA approved Celebrex (celecoxib) in 1999 at the same time as Vioxx
(rofecoxib). As the Lancet explains, "their debut was announced in 2000 in the
medical literature with two landmark trials: VIGOR for rofecoxib, and CLASS
for celecoxib. Subsequently, a number of second generation COX-2 inhibitors
have been developed. These include valdecoxib, parecoxib, etoricoxib, and
lumiracoxib. The indications for their use have remained largely unchanged and
more 'me-too' COX-2 inhibitors are on the horizon."

Third generation versions are being tested. Last month Ohio researchers
announced that a drug labeled OSU03012, which they describe as "a bioavailable
third generation celecoxib derivative . . . that potently induces apoptosis in
prostate cancer cell lines and is being developed as an anti-cancer therapy in
the NCI Rapid Access to Interventional Therapy (RAID)," is cytotoxic against a
type of leukemia (CLL) and type B lymphoma.

Celecoxib (Celebrex) May Foil Recurrent Prostate Cancer: Presented at ACS
By Mike Fillon

NEW ORLEANS, LA -- October 13, 2004 – Celecoxib (Celebrex), a commonly
prescribed anti-inflammatory drug, might slow progression of recurrent
prostate cancer, according to results of a study presented here on October
10th at the American College of Surgeons 90th Annual Clinical Congress.

The researchers say this is the first time a cyclooxygenase 2 (COX-2)
inhibitor, in this case, celecoxib, has been shown to have a therapeutic
effect in prostate cancer at any stage of the disease.

"The potential for anti-inflammatory medicines to have an antitumor effect has
been observed for some time. We're just at the beginning of understanding the
possibilities," said Raj Pruthi, MD, Assistant Professor of Surgery/Urology,
University of North Carolina, Chapel Hill.

Dr. Pruthi presented the results on behalf of the research team, led by J.
Eric Derksen, MD, also of University of North Carolina at Chapel Hill, during
the Forum on Fundamental Surgical Problems focusing on Urological/Reproductive
Surgery.

Results of the study showed that levels of prostate specific antigen (PSA)
stabilized, were maintained, or declined in 92% of 24 men who took celecoxib
twice a day for a year. Dr Pruthi said the COX-2 enzyme is involved in
prostaglandin synthesis, cell proliferation, and angiogenesis in a variety of
disease processes.

Although 71% of the men in the study had a moderate or high increase in PSA
levels before treatment, after 3 months of treatment with celecoxib 400 mg or
800 mg twice a day 92% of men had a slow rate of increase, maintained their
levels or had a decrease in their levels. At the end of a year of therapy, one
man (4%) had a high rate of increase of PSA, and three (13%) had a moderate
rise in PSA. The remaining 83% of men had slow rate of increase, stable
levels, or decreased levels.

Other investigators are studying the use of COX-2 inhibitors as antitumor
medications for a variety of cancers. According to Dr. Pruthi, the National
Cancer Institute sponsored 13 studies on the use of COX-2 inhibitors for
colon, prostate, and breast cancer in 2003 and 34 in 2004 on cancers of the
head and neck, lung, and bladder.

Interest in COX-2 inhibitors as a potential cancer treatment is increasing
because of their ability to interfere with the body's repair mechanism, which
is out of control in the presence of cancer. "The COX-2 enzyme is not normally
expressed in the body," said Dr. Pruthi. "But if there is illness or injury,
the body begins to produce COX-2 to increase blood flow, create inflammation,
and promote epithelial cell growth that will help it heal."

Dr. Pruthi added that the same processes occur in tumor development --
excessive cell growth, angiogenesis (blood vessel generation), and excessive
inflammation with cellular mediators and growth factors. "Drugs that inhibit
COX-2 appear to work to prevent angiogenesis and to promote apoptosis (natural
programmed cell death)."

Dr. Pruthi said the potential role of COX-2 inhibitors in men with prostate
cancer is supported by large-scale epidemiological investigations as well as
animal studies. Population studies have shown that men who take
anti-inflammatory drugs have less than half the risk of developing prostate
cancer than men who don't take these drugs. In animal experiments, prostate
tumors have shrunk in size by a factor of 10 after being exposed to a COX-2
inhibitor.

Dr. Pruthi said his team is testing celecoxib in other groups of men with
prostate cancer. He is planning a study of the drug as adjuvant therapy in men
with advanced disease as well as those at high risk for recurrence immediately
after surgery.

"The studies haven't been done yet, but it is interesting to think about
giving a COX-2 inhibitor to men with advanced disease who were not
successfully treated with hormonal therapy. Those are the worst of the worst
cases of prostate cancer patients," said Dr. Pruthi. "Even more exciting is to
contemplate using the drug as a chemopreventive agent, before a man even gets
prostate cancer."

Pfizer Inc. provided the drug used in this study.

[Presentation title: "A Phase II Trial of Celecoxib in PSA Recurrent Prostate
Cancer After Definitive Radiation Therapy (XRT) or Radical Prostatectomy
(RP)." Session code SF-UR]

Celebrex Provides A Two Pronged Attack Against Prostate Cancer
PHILADELPHIA -- Celecoxib, a selective COX-2 inhibitor with promising
anti-cancer properties, has now been found to attack prostate cancer cells in
a second way that differs from Vioxx (rofecoxib), another anti-inflammatory
drug that also inhibits COX-2.

In studies published in the March 1 issue of the journal Clinical Cancer
Research, scientists at the Weill Medical College of Cornell University
revealed that celecoxib, marketed under the name Celebrex, not only targets
COX-2, but also reduces levels of a key protein, cyclin D1, that's critical
for cell replication.

"It is well established that COX-2 is a significant and rational target for
anti-cancer therapy," said Andrew Dannenberg, M.D., director of cancer
prevention at the Weill Medical College of Cornell University and senior
author of the paper.

"These studies suggest that celecoxib exerts a second mode of action
independent of its known anti-inflammatory mechanism that imposes further
restrictions on the proliferation of prostate cancer cells. The results
provide potentially important insights into our understanding of the overall
anti-tumor activity of selective COX-2 inhibitors."

Dannenberg and a team of investigators discovered this new mechanism by
applying celecoxib to prostate cancer cells that failed to express COX-2.
Here, the scientists observed that the celecoxib-treated cancer cells did not
replicate as rapidly as untreated cells. After further analysis, they found
the drug worked by suppressing amounts of cyclin D1, a protein that's
essential if cells are to grow, divide and spread.

The scientists also attempted to replicate the experiment with Vioxx
substituting for celecoxib. In this case, the prostate cancer cells continued
to flourish.

"These results support the notion of a unique action by celecoxib that is
independent of COX-2, and that's different from Vioxx," said Dannenberg.

"These beneficial effects were observed at concentrations of celecoxib that
occur in humans," added Dannenberg. "This increases the likelihood that our
findings are clinically relevant."

Dannenberg and his colleagues then demonstrated that celecoxib worked in
animals that served as hosts for human prostate tumors. In this animal model,
celecoxib not only was shown to reduce proliferation of cancer cells, but also
reduced the growth of blood vessels at the tumor sites. As a result, tumor
mass and blood vessel density in the treated animals was about half that
observed in the untreated animals.

Contributing to the studies, along with Dannenberg, were Kotha Subbaramaiah,
Baoheng Du and Mindy Chang from Weill Medical College of Cornell University,
New York, N.Y.; Manish Patel, Carlos Cardon-Cardo, and Howard Thaler, Memorial
Sloan-Kettering Cancer Center, New York, N.Y.; and Peiying Yang and Robert
Newman, UT M.D. Anderson Cancer Center, Houston, Texas.

###

Founded in 1907, the American Association for Cancer Research is a
professional society of more than 24,000 laboratory, translational, and
clinical scientists engaged in all areas of cancer research in the United
States and in more than 60 other countries. AACR's mission is to accelerate
the prevention and cure of cancer through research, education, communication,
and advocacy. Its principal activities include the publication of five major
peer-reviewed scientific journals: Cancer Research; Clinical Cancer Research;
Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer
Epidemiology, Biomarkers & Prevention. AACR's Annual Meeting attracts more
than 15,000 participants who share new and significant discoveries in the
cancer field. Specialty meetings, held throughout the year, focus on the
latest developments in all areas of cancer research.

.

Celebrex Bests Vioxx as Potential Cancer Fighter
Despite cardiovascular risks, painkiller appears to block key protein for
cancer cell replication

By Steven Reinberg
HealthDay Reporter

TUESDAY, March 1 (HealthDayNews) -- Celebrex, one of the cox-2 painkillers
under fire for increasing heart attack and stroke risk, may actually slow
certain cancers in a way that its cousin, Vioxx, does not, according to new
preliminary research.

Both drugs, known as cox-2 inhibitors, have already been shown to inhibit the
growth of tumors that depend on the cox-2 enzyme, as happens with some
prostate and breast cancers.

 

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But a new study finds that Celebrex (celecoxib) appears to fight prostate
cancer on another front, by blocking a key protein that is essential to the
replication of cancer cells. This latest report appears in the March 1 issue
of Clinical Cancer Research.

"Celecoxib can mediate anti-tumor effects by mechanisms in addition to
targeting cox-2, which is its known target," said lead researcher Dr. Andrew
Dannenberg, director of cancer prevention at the Weill Medical College of
Cornell University in New York City. "This suggests that the agent's overall
anticancer activity may reflect cox-2 inhibition and other properties."

In their study, Dannenberg's team treated human prostate cancer cells that did
not have the cox-2 enzyme with Celebrex. The researchers found that cells
treated with the drug did not reproduce as quickly as similar untreated cells.
Further research determined that Celebrex was blocking cyclin D1.

"We were able to demonstrate that at clinically achievable concentrations of
the drug in cells that don't express cox-2, the drug still has activity,"
Dannenberg said. "Based on these results, it's conceivable it will have
effects in human tumors that do or do not express cox-2," he added.

However, when the researchers tried the same experiment using Vioxx, they
found the cancer cells continued to reproduce.

"This makes the point that all cox-2 inhibitors are not created equal,"
Dannenberg said.

They were, however, given equal treatment two weeks ago, when a U.S. Food and
Drug Administration advisory panel voted to recommend that Celebrex, Vioxx and
Bextra stay on the market, while acknowledging the cardiovascular dangers of
the drugs.

On Tuesday, the Louisiana health department announced it will impose
additional safeguards, which will go into effect on March 15. Those safeguards
will require doctors to supply a diagnosis code for every prescription for
both Celebrex and Bextra, telling the pharmacist why the patient needs the
medication.

Vioxx is not affected because it was removed from pharmacy shelves last fall
by its manufacturer after trials revealed the heart risks.

Despite the concerns about the cardiac risk of cox-2 inhibitors, Dannenberg
believes that when it comes to cancer, the considerations of these drugs'
ability to fight tumors should be the first priority.

"Cox-2 inhibitors have been shown to have a small increase in risk of
cardiovascular complications when taken long term," Dannenberg noted.
"However, it is extremely important in the oncology world to recognize that
efficacy is of greater concern. This new study makes the observation that
celecoxib can act by more than a single mechanism to inhibit tumor growth."

Dannenberg noted that his work is not a clinical study, and that the use of
Celebrex in fighting cancer needs to wait for the outcome of several ongoing
clinical trials.

"Decision-making on clinical use should be based on the results of these
clinical trials," he said.

Another expert thinks that much more needs to be done before Celebrex can find
a role in fighting cancer.

"It is surprising to me that the authors did not try to see what would happen
to these cells when treated with aspirin or one of the inhibitors which block
cox-1 specifically, since these cells did express cox-1," said Dr. Raymond N.
DuBois, the director of the Vanderbilt-Ingram Comprehensive Cancer Center at
Vanderbilt University.

"We have found that some ovarian cancer cells are very dependent on cox-1
expression, and respond very well to cox-1 inhibitors," DuBois added.

DuBois noted that in the study, higher doses of Celebrex seemed to be more
effective.

"Unfortunately, these higher doses in humans seem to be associated with
adverse cardiovascular effects," he added. "Thus, these selective inhibitors
may have some role in treatment of prostate cancer, but their long-term use
for prevention at these higher doses may not be well-tolerated."

One heart expert said he thought that the use of cox-2 inhibitors to fight
cancer was a tricky matter.

"We currently do use many drugs for cancer treatment that are themselves toxic
to the heart," said Dr. Scott D. Solomon, director of noninvasive cardiology
at Brigham and Women's Hospital, in Boston. "Ultimately, I believe we will
need large clinical trials to sort this out, with longer follow-up times,
since a large enough trial should provide the 'net' between efficacy and
safety."

Moreover, Solomon is concerned with the ultimate benefit to patients.

"Another thing to remember, though, is whether a reduction in cancer cell
proliferation as suggested here will result in net benefit to the patient,
such as longer life," he said. "This will be necessary to offset any potential
increased cardiovascular risk. In short, this is simply more information to
fill out our current knowledge of the possible benefits of cox-2 inhibitors."

More information

The American Cancer Society can tell you more about new cancer treatments (
www.cancer.org target =_new).

 

SOURCES: Andrew Dannenberg, M.D., director, cancer prevention, Weill Medical
College of Cornell University, New York City; Raymond N. DuBois, M.D., Ph.D.,
director, Vanderbilt-Ingram Comprehensive Cancer Center, B.F. Byrd Jr.,
professor, molecular oncology, medicine, cancer biology and cell-developmental
biology, Vanderbilt University Medical Center, Nashville, Tenn.; Scott D.
Solomon, M.D., director, noninvasive cardiology, Brigham and Women's Hospital,
and associate professor, medicine, Harvard Medical School, Boston; March 1,
2005, Clinical Cancer Research

Copyright © 2005 ScoutNews LLC. All rights reserved.
Last updated 3/1/2005

Popular Painkiller May Slow Prostate Cancer

Cox-2 Inhibitors -- Such as Celebrex -- May Delay, Prevent Cancer Progression
By Jeanie Lerche Davis
WebMD Medical News  Reviewed By Michael Smith, MD
on Friday, June 11, 2004  


June 11, 2004 -- The commonly prescribed painkiller Celebrex may slow prostate
cancer growth, new research shows.

Drugs known as Cox-2 inhibitors, including Celebrex, have been shown to have
anti-tumor effects on a variety of different cancer tissues, including colon,
breast, lung, and prostate cancers, explains researcher J. Eric Derksen, MD, a
urologist with the University of North Carolina at Chapel Hill.

Cox-2 inhibitors (commonly used to treat arthritis) relieve pain,
inflammation, and swelling by blocking the body's production of an enzyme
called Cox-2. These drugs, which also include Bextra and Vioxx, are less
irritating on the stomach lining than earlier versions of anti-inflammatory
drugs, like ibuprofen.

Recent research involving men treated for prostate cancer has shown especially
promising results, says Derksen, who presented his findings at the American
Society of Clinical Oncology's annual meeting this week in New Orleans.

In his study, Derksen enrolled 24 men who had rising PSA (prostate-specific
antigen) levels, a marker for prostate cancer growth, despite treatment with
radiation therapy or prostate removal surgery. The men took either 400
milligrams or 800 milligrams of Celebrex for one year. Their PSAs were checked
at several points during that year.

Celebrex had a positive effect on nearly all (92%) of the men after three
months, reports Derksen. Overall, PSA declined in eight of the men and
remained the same in three. The rise in PSA levels slowed in 11 men,
indicating that their prostate cancer was growing more slowly. The two
remaining men had no improvement at three months but the rise in their PSA
levels slowed by one year.

It's a hopeful finding: The other option involves shutting down production of
male sex hormones -- usually with medication -- which has not proven
successful in slowing prostate cancer or improving a man's chances of
survival. Also men in the early stages of prostate cancer recurrence, such as
the men in this study with rising PSA levels, usually have no symptoms.
Therefore, shutting down production of male sex hormones could unnecessarily
expose them to side effects, say the researchers.

"These results show that Cox-2 inhibitors may help delay or prevent [prostate
cancer] progression in these patients," he writes.

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

SOURCES: American Society of Clinical Oncology 2004 annual meeting, New
Orleans, June 5-8, 2004. News release, University of North Carolina School of
Medicine.

NSAID's Statin Drugs and Prostate Cancer

Frequently the PSA may be high because of an a prostate infection called
"Prostatitis". This infection can be cause by a bacteria or other non-bacteria
causes. For a bacteria caused prostatitis the antibiotic drug Cipro is
frequently prescribed by a doctor. According to many doctors, this should be
prescribed for 5 to 6 weeks and then another PSA would be taken. We have seen
a PSA drop from 60 down to 7 after Cipro treatment. In addition is my own case
as I was recovering from the "bump" following my SI/EBRT, I treated myself
with a NSAID (Ibuprofen) only and had my PSA drop from 1.23 to 0.7 - a drop of
43% in two weeks. The following is a discussion of NSAID's and there positive
effects on prostate cancer in general. You can see the report of my experiment
at The PSA bounce following Brachytherapy

It is thought that these drugs may help reduce prostate cancer incident in a
study done in New Zealand, (Int J Cancer 1998 Aug 12;77(4):511-5) in which
they said: "a trend toward reduced risks of advanced prostate cancer
associated with regular use of total NSAIDs (RR = 0.73; 95% CI 0.50-1.07) and
total aspirin (RR = 0.71; 95% CI 0.47-1.08). However, these associations
failed to reach statistical significance at the usually accepted levels. "
Note that they think there may be a reduced risk of advance prostate cancer
associated with the regular use of NSAIDs.

In another study (Oncol Rep 2000 Jan-Feb;7(1):169-70 ) they said: "We examined
the association of prostate cancer and non-steroidal anti-inflammatory drugs
(NSAIDs) in a case control study of 417 prostate cancer patients and 420
group-matched control subjects. Regular daily use of over the counter NSAIDs,
ibuprofen or aspirin, was associated with a 66% reduction in prostate cancer
risk (odds ratio = 0.34, 95% confidence interval = 0.23-0.58, p<0.01). The
risk of prostate cancer was also significantly reduced in men who reported
taking prescription NSAIDs (odds ratio = 0.35, 95% confidence interval =
0.15-0.84, p<0.05). These results suggest that NSAIDs may have value in the
chemoprevention of prostate cancer"

And yet in another study ( Clin Cancer Res 1998 Mar;4(3):763-71) they found:
"Recent clinical observations indicate that ibuprofen may alleviate the
radiation-induced dysuria that almost invariably occurs during radiation
therapy for prostate cancer. Because the use of ibuprofen could consequently
become common during radiation therapy for prostate cancer, we have been
interested in the potential interactions between ibuprofen and ionizing
radiation on prostate tumor cells. The effects of gamma-irradiation and/or
ibuprofen on PC3 and DU-145 human prostate carcinoma cells were evaluated in
vitro using three model systems. Clonogenic survival was determined by plating
cells 24 h after treatment of nearly confluent monolayers. Analysis of cell
growth, cell detachment, and apoptotic cell death was carried out over a
period of up to 9 days after treatment of PC3 and DU-145 monolayers. The
effect of ibuprofen and/or radiation was also probed by observing the
inhibition of growth of established PC3 and DU-145 colonies that were treated
on the 14th day of colony growth. Ibuprofen enhanced the radiation response of
prostate cancer cells in all three in vitro models. Both the cytotoxic and
radiosensitizing effects of ibuprofen seem to require concentrations that are
higher than those reported to inhibit prostaglandin synthesis, suggesting that
other molecular mechanisms may be responsible for ibuprofen cytotoxicity."

The NSAID's hold some fascination for me, since they appear to be at least
somewhat antiangiogenesis. I have read and thought about there action during
radiation. I have confirmed, by my reduced PSA during the bump, there effect
on inflammation, etc. see http://www.prostate-help.org/c abounc.htm. I have
had other men report a similar reaction. It has jokeingly been referred to as
the "Cooley Protocol".

A popular arthritis drug, Celebrex, recently was approved by the U.S. Food and
Drug Administration for the prevention of precancerous polyps that lead to an
inherited form of colon cancer. This is in that class. It has been know that
these NSAID drugs inhibit both COX-1 and COX-2 and derive their toxicity from
COX-1 inhibition. However it is my understanding that Celebrex is a very
strong in its inhibiting of COX-2 a good thing.

"The molecular identification of a second is a form of cyclooxygenase-2
(COX-2) led to a major investment by several pharmaceutical companies in the
development of selective inhibitors. The central tenets of the rationale for
developing selective COX-2 inhibitors are that prostaglandins that contribute
to inflammation are derived from COX-2, whereas prostaglandins that are
involved in normal physiological processes are derived from the constitutively
expressed isoform COX-1. There is now considerable evidence that COX-2 is
actually expressed constitutively in many tissues and performs important
physiological functions. Thus, suppression of COX-2 with selective inhibitors
should not be expected to be without some adverse consequences. Moreover,
there is strong evidence that COX-1 contributes to inflammation and pain, so
selective inhibition of COX-2 will not necessarily produce the same degree of
efficacy that is seen with mixed inhibitors of COX-1 and COX-2." (Am J Med
1999 Dec 13;107(6A):11S-16S; discussion 16S-17S)

ANOTHER PRESS RELEASE

Arthritis Drugs Inhibit Breast Tumors, Ohio Study Reports Prostate Tests
Expected

August 16, 2000. COLUMBUS, Ohio - A COX-2 inhibitor drug called Celebrex and
to lesser extent the over-the-counter NSAID ibuprofen, both commonly used to
treat the symptoms of arthritis, reduce the number and the size of cancerous
breast tumors in animals.

Celebrex and other NSAIDs have positive activity against colon cancer polyps,
previous studies have shown. Celebrex may also have some activity against lung
tunors. Tests for prostate and other cancers are expected to follow.

NSAIDs do not have "direct cytotoxic effect," according to studies in dogs.
They are thought to slow and diminish new tumor growth by disrupting formation
of new tumor blood supplies (angiogenesis).

The latest study in rats examined the effectiveness of Celebrex (chemical name
celecoxib) in fighting breast cancer. When compared with a control group, rats
who were fed celecoxib had a 68 percent decrease in tumor incidence and an 81
percent decrease in average tumor size.

The researchers describe the effects of Celebrex as "striking." Ibuprofen,
they add, "also produced significant effects, but of lesser magnitude."

While the drug's anti-tumor effects have yet to be tested in humans in a
clinical trial, researchers at Ohio State University say celecoxib shows great
promise as a tool that someday may help treat and even prevent breast cancer.
Celecoxib belongs to the family of nonsteroidal anti-inflammatory drugs
(NSAIDs), which include the pain-reducers aspirin and ibuprofen.

The research appears in a recent issue of the journal Cancer Research.

"Across the board, regular intake of NSAIDs lowers the risk of breast cancer,"
said Randall Harris, co-author of the study and a professor of epidemiology at
Ohio State. "NSAIDs inhibit an enzyme that is produced by a gene that is
normally silent in breast tissue. Too much of this enzyme in breast tissue
leads to the initiation and promotion of breast cancer."

The culprit enzyme, cyclooxygenase-2 (COX-2), is normally triggered only
during the body's response to foreign invaders, such as viruses and bacteria.
But for reasons unknown to researchers, there is a proliferation of COX-2 in
the breast tissue of patients with breast cancer, Harris said. This abundance
causes a "prostaglandin cascade" - a flow of biochemicals that fights
invaders. Prostaglandins are hormone-like compounds in the body that initiate
the body's immune response.

NSAIDs turn off the prostaglandin cascade, Harris said. "There is something
about COX-2 and the ensuing cascade that encourages carcinogenesis, and
celecoxib seems to turn it around."

Harris and his colleagues separated 120 female rats into three treatment
groups. Forty received 1,500 mg of celecoxib for every kilogram of food in
their diet; 40 received an equivalent amount of ibuprofen per kilogram of
their diet; and 40 served as the control group, receiving only a powdered
diet. The drug dosages given to rats in this study were comparable to the
average daily therapeutic dose of either drug for a human - about 100 to 200
mg.

After seven days on the respective diets, each rat was injected with DMBA, a
carcinogen which causes breast tumors. The diets were continued for 105 more
days.

At 28 days after the DMBA injection, the researchers examined the rats for
tumors. "It takes at least four to five weeks for the tumors to become large
enough to detect by palpation," Harris said. At the end of the experiment, all
animals were sacrificed and the tumors extracted and measured.

The researchers found that 13 of the 40 rats given celecoxib had developed
malignant tumors, while 24 of the 40 rats in the ibuprofen group developed
cancerous tumors. Each of the 40 rats in the control group had developed
malignant tumors; many animals in this group had also developed multiple
tumors.

Researchers detected the majority of tumors in the celecoxib group much later
than they did in the control group (95 vs. 58 days). In the ibuprofen group,
most of the tumors were detected at 86 or more days after DMBA injection.

Harris also noted that the rats that had received celecoxib experienced no
toxic side effects sometimes associated with NSAIDs, such as weight loss,
ulcers or bleeding.

"Ten to 20 percent of women aged 50 and older use NSAIDs on a regular basis,"
Harris said. "Not only are these drugs potentially important for breast cancer
prevention and control, they may also have significant value in the prevention
and therapy of other cancers, too, such as cancers of the colon, lung and
prostate."

This research was supported in part by Searle Research and Development, St.
Louis, the manufacturer of celecoxib, and in part by Ohio State. (the Center
of Molecular Epidemiology and Environmental Health, the Comprehensive Cancer
Center, the School of Public Health and the Department of Surgery.)

1. Harris conducted the research with Galal Alshafie, a graduate student in
the School of Public Health at Ohio State; Hussein Abou-Issa, an associate
professor of surgery at Ohio State; and Karen Seibert, director of COX-2
research at Searle Monsanto Research and Development.
2. Links Harris RE, Alshafie GA, Abou-Issa H, Seibert K. Chemoprevention of
breast cancer in rats by celecoxib, a cyclooxygenase 2 inhibitor. Cancer Res.
2000 Apr 15;60(8):2101-3.
3. Reddy BS, et al. Chemoprevention of colon cancer by specific
cyclooxygenase-2 inhibitor, celecoxib, administered during different stages of
carcinogenesis. Cancer Res. 2000 Jan 15;60(2):293-7.
4. Masferrer JL, et al. Antiangiogenic and antitumor activities of
cyclooxygenase-2 inhibitors. Cancer Res. 2000 Mar 1;60(5):1306-11. 5. Genetic
alterations in human prostate cancer: a review of current literature. Ozen M,
Pathak S Department of Cancer Biology, University of Texas M. D. Anderson
Cancer Center, Houston 77030, USA.
6. Alshafie GA, Harris RE, et al. Comparative chemopreventive activity of
ibuprofen and N-(4-hydroxyphenyl) retinamide against the development and
growth of rat mammary adenocarcinomas. Anticancer Res. 1999
Jul-Aug;19(4B):3031-6.

Celebrex provides a two pronged attack against prostate cancer
PHILADELPHIA--Celecoxib, a selective COX-2 inhibitor with promising
anti-cancer properties, has now been found to attack prostate cancer cells in
a second way that differs from Vioxx (rofecoxib), another anti-inflammatory
drug that also inhibits COX-2.
In studies published in the March 1 issue of the journal Clinical Cancer
Research, scientists at the Weill Medical College of Cornell University
revealed that celecoxib, marketed under the name Celebrex, not only targets
COX-2, but also reduces levels of a key protein, cyclin D1, that's critical
for cell replication.

"It is well established that COX-2 is a significant and rational target for
anti-cancer therapy," said Andrew Dannenberg, M.D., director of cancer
prevention at the Weill Medical College of Cornell University and senior
author of the paper.

"These studies suggest that celecoxib exerts a second mode of action
independent of its known anti-inflammatory mechanism that imposes further
restrictions on the proliferation of prostate cancer cells. The results
provide potentially important insights into our understanding of the overall
anti-tumor activity of selective COX-2 inhibitors."

Dannenberg and a team of investigators discovered this new mechanism by
applying celecoxib to prostate cancer cells that failed to express COX-2.
Here, the scientists observed that the celecoxib-treated cancer cells did not
replicate as rapidly as untreated cells. After further analysis, they found
the drug worked by suppressing amounts of cyclin D1, a protein that's
essential if cells are to grow, divide and spread.

The scientists also attempted to replicate the experiment with Vioxx
substituting for celecoxib. In this case, the prostate cancer cells continued
to flourish.

"These results support the notion of a unique action by celecoxib that is
independent of COX-2, and that's different from Vioxx," said Dannenberg.

"These beneficial effects were observed at concentrations of celecoxib that
occur in humans," added Dannenberg. "This increases the likelihood that our
findings are clinically relevant."

Dannenberg and his colleagues then demonstrated that celecoxib worked in
animals that served as hosts for human prostate tumors. In this animal model,
celecoxib not only was shown to reduce proliferation of cancer cells, but also
reduced the growth of blood vessels at the tumor sites. As a result, tumor
mass and blood vessel density in the treated animals was about half that
observed in the untreated animals.

Contributing to the studies, along with Dannenberg, were Kotha Subbaramaiah,
Baoheng Du and Mindy Chang from Weill Medical College of Cornell University,
New York, N.Y.; Manish Patel, Carlos Cardon-Cardo, and Howard Thaler, Memorial
Sloan-Kettering Cancer Center, New York, N.Y.; and Peiying Yang and Robert
Newman, UT M.D. Anderson Cancer Center, Houston, Texas.

Celebrex Bests Vioxx as Potential Cancer Fighter
Despite cardiovascular risks, painkiller appears to block key protein for
cancer cell replication

By Steven Reinberg
HealthDay Reporter

TUESDAY, March 1 (HealthDayNews) -- Celebrex, one of the cox-2 painkillers
under fire for increasing heart attack and stroke risk, may actually slow
certain cancers in a way that its cousin, Vioxx, does not, according to new
preliminary research.

Both drugs, known as cox-2 inhibitors, have already been shown to inhibit the
growth of tumors that depend on the cox-2 enzyme, as happens with some
prostate and breast cancers.


But a new study finds that Celebrex (Celecoxib) appears to fight prostate
cancer on another front, by blocking a key protein that is essential to the
replication of cancer cells. This latest report appears in the March 1 issue
of Clinical Cancer Research.

"Celecoxib can mediate anti-tumor effects by mechanisms in addition to
targeting cox-2, which is its known target," said lead researcher Dr. Andrew
Dannenberg, director of cancer prevention at the Weill Medical College of
Cornell University in New York City. "This suggests that the agent's overall
anticancer activity may reflect cox-2 inhibition and other properties."

In their study, Dannenberg's team treated human prostate cancer cells that did
not have the cox-2 enzyme with Celebrex. The researchers found that cells
treated with the drug did not reproduce as quickly as similar untreated cells.
Further research determined that Celebrex was blocking cyclin D1.

"We were able to demonstrate that at clinically achievable concentrations of
the drug in cells that don't express cox-2, the drug still has activity,"
Dannenberg said. "Based on these results, it's conceivable it will have
effects in human tumors that do or do not express cox-2," he added.

However, when the researchers tried the same experiment using Vioxx, they
found the cancer cells continued to reproduce.

http://www.prostateforum.com/backissues.htm

Volume 8 Number 11, Updates On RP; The Celebrex Controversy: Radical
Prostatectomy Revisited - One of the therapies that has been examined more
closely this past year is radical prostatectomy (RP). In fact, researchers
have spent so much time studying RP that they have more information on it than
any other treatment option for newly diagnosed patients. So it’s now possible
for us to have a much more accurate discussion of the strengths and limits.

Volume 8 Number 10, Vitamin E - Vioxx, Bextra & Celebrex. Grape Juice: Recent
news about vitamin E has forced us to revisit the benefits of this supplement
and chime in on the current evidence about the safe and effective dosage for
men with prostate cancer as well as for their loved ones.

Volume 6 Number 12, Slowing Prostate Cancer Growth: December 2001 (Published
October 2002) Proscar delays prostate cance reappearance after intermittent
hormonal therapy. High doses of calcitriol may significantly increase the
effectiveness of selected chemotherapy drugs. Dostinex reduces prostate
cancer's growth rate without causing any significant side effects. Celebrex
kills cancer cells (particularly prostate cancer cells) in the laboratory by
blocking the action of IGF-1, a factor needed for cancer cell survival. In the
laboratory, the major fat in fish oil kills prostate cancer cells. Thalidomide
slows the progression of prostate cancer, but has serious side effects.

Celebrex has second anti-cancer property

Philadelphia, PA, Mar. 1 (UPI) -- New York researchers say Celecoxib, a
selective COX-2 inhibitor also known as Celebrex, attacks prostate cancer
cells in two distinct ways.


A Cornell University team, in a study published in the March 1 issue of the
journal Clinical Cancer Research, found that Celecoxib attacks prostate cancer
cells a second way that differs from Vioxx, another anti-inflammatory drug
that also inhibits COX-2.

Besides targeting COX-1, Celecoxib also reduces levels of a key protein,
cyclin D1, that's critical for cell replication.

"It is well established that COX-2 is a significant and rational target for
anti-cancer therapy," said Andrew Dannenberg, M.D., director of cancer
prevention at the Weill Medical College of Cornell University.

"These studies suggest that Celecoxib exerts a second mode of action
independent of its known anti-inflammatory mechanism that imposes further
restrictions on the proliferation of prostate cancer cells. The results
provide potentially important insights into our understanding of the overall
anti-tumor activity of selective COX-2 inhibitors."

A Food and Drug Administration committee studying the link between COX-2 drugs
and the risk of heart attack and stroke recommended the drugs remain on the
market.

A more promising approach is to identify drugs that work directly on Akt or on
PI3 kinase, the protein that activates Akt. The drugs wortmannin and LY294002
are widely used in the laboratory to block activation of Akt by inhibiting PI3
kinase. These drugs are very effective in triggering the suicide program in
prostate cancer cells. I am aware of several major pharmaceutical firms who
are developing Akt inhibitors with the hope of finding a useful anticancer
agent. One drug already on the market, Celebrex®, has been reported to block
Akt function and cause the death of human prostate cancer cell lines.
Celebrex® is widely used (and is FDA-approved) for treating arthritis; it is
also much less toxic than most anticancer agents.

http://www.prostate-cancer.org/education/andeprv/Myers_AndrogenResistance2.
html

Celebrex Alters Gene Activity in the Colon

The drug celecoxib (Celebrex), a COX-2 inhibitor, produces a distinct pattern
of gene activity in the normal colons of patients at risk for an inherited
form of colon cancer, according to results of a study reported at the AACR
annual meeting.

The researchers identified a genetic "signature" based on 173 genes whose
activity was altered by the drug, including many genes involved in the immune
system and inflammatory response. Overall, celecoxib led to changes in more
than 1,400 genes in the colon, according to Dr. Oleg Glebov, an NCI research
fellow.

The signature may be the first indicator of whether the drug has effects in
the colon. The researchers note that increasing the dose was associated with
larger changes in gene activity, suggesting a dose-response effect.

"We can distinguish individuals who take celecoxib on a routine basis from
those who do not," says Dr. Ilan Kirsch, Genetics Branch chief in NCI's Center
for Cancer Research, who led the study. "The distinct pattern of gene activity
implies that there could be a direct or indirect action of the drug on
pathways of immune responsiveness, inflammation, and proliferation within the
colon."

The researchers tested celecoxib in patients at risk for hereditary
nonpoly-posis colon cancer. Also known as Lynch Syndrome, the disorder
increases the risk of colorectal, ovarian, and endometrial cancers, among
others.

DLC-1 Gene Implicated in Prostate Cancer

The tumor suppressor gene DLC-1 (deleted in liver cancer-1) is often silenced
in both prostate cancer and benign prostatic hyperplasia (BPH), according to a
study presented at the AACR annual meeting. Dr. Nicholas Popescu and
colleagues in NCI's CCR found that the DLC-1 promoter region was
hypermethylated in a high number of prostate tumor and BPH samples, thus
keeping the gene turned off and resulting in abnormal cell growth.

Loss of DLC-1 expression has been associated with liver, breast, and ovarian
cancer, among others. Because the chromosome region that contains DLC-1 is
often deleted in prostate tumors, DLC-1 might be associated with prostate
cancer as well. DNA methylation is one way to keep genes turned off, and Dr.
Popescu's lab identified DLC-1 hypermethylation in 11 of 20 prostate
adenocarcinomas and 15 of 21 BPHs. In studies with two prostate cancer cell
lines, the researchers found that histone deacetylation can also result in
loss of DLC-1 expression. Increased DLC-1 methylation in BPH samples also
correlated with increased levels of prostate-specific antigen in the blood.

"Because abnormal methylation is one of the earliest alterations in tumor
development, the detection of DLC-1 promoter hypermethylation may have
clinical application for early detection of prostate cancer," noted Dr.
Popescu.

VITAMIN D, NSAIDS PROVIDE DOUBLE WHAMMY AGAINST PROSTATE CANCER, STANFORD
STUDY FINDS
STANFORD, Calif. – The growth of prostate cancer cells can be halted by
combining a form of vitamin D, available only by prescription, with low doses
of an over-the-counter painkiller, researchers at the Stanford University
School of Medicine have found. The combination reduced prostate cancer cell
growth in a laboratory dish by up to 70 percent, according to the findings,
published in the Sept. 1 issue of Cancer Research.

The study’s senior author, David Feldman, MD, professor of medicine, who has
been studying vitamin D for 25 years, had shown in previous studies that a
form of the vitamin, known as calcitriol, limits the growth of prostate cancer
cells. Calcitriol, the active form of vitamin D, is the metabolite that is
created in the body after consumption of vitamin D-containing food or exposure
to the sun.

Feldman wanted to see if he could boost calcitrol’s effects and lower the dose
by using it in conjunction with another drug. He and his colleagues, including
professor of urology Donna Peehl, PhD, who specializes in developing models of
prostate cancer in cultured cells, found that by using calcitriol with
nonsteroidal anti-inflammatory drugs, or NSAIDs, they could suppresses
prostate cancer growth in vitro even more—and with smaller doses—than using
either drug alone.

“There is great enhancement when the drugs are given together, using what we
think is a safe dose in humans,” said Feldman. “It’s hard to make an exact
comparison, as we are talking about cells in a dish and not a person.” Still,
based on the findings, he and his colleagues have already begun a clinical
trial in men who have a post-treatment recurrence of prostate cancer. Both
calcitriol and nonselective NSAIDs have been used in humans for years, and the
safety and risks of these drugs are well known.

According to the Centers for Disease Control and Prevention, nearly 30,000 men
die annually in the United States from prostate cancer. Among cancers, only
lung cancer kills more men. Although prostate cancer is often a slow-growing,
noninvasive type of cancer, there are some cases where a deadly migration of
cancer cells invades other parts of the body. The standard treatment for such
cases is hormone therapy, but that treatment ultimately does not work for most
patients. Slowing the growth of the prostate cancer cells could buy time for
patients before beginning this last-ditch therapy.

Over the course of Feldman’s years of vitamin D research, he and others had
determined that the vitamin has several actions that make it useful in cancer
therapy. While a great deal is now known about these effects, there is still
much to be learned about how the vitamin stymies tumor growth.

To get an idea of what calcitriol does on a genetic level to halt tumor
growth, the researchers used a cDNA microarray, a tool that provides an
overview of the genetic changes that occur when prostate cancer cells react to
calcitriol. The researchers discovered that two of the affected genes are
critical in the production and breakdown of prostaglandins—hormones that cause
a range of physiological effects, including inflammation. Inflammation, in
turn, is also associated with cancer growth.

Like calcitriol, NSAIDs also block prostaglandin production. Thus, it seemed
logical to test calcitriol in various combinations with NSAIDs to see if the
double whammy could knock out prostate cancer better than either drug alone,
explained study leader Jacqueline Moreno, PhD, a postdoctoral scholar in
Feldman’s lab.

When the researchers began the study, which was done on cells in culture, they
were using selective NSAIDs, such as Vioxx and Celebrex. These drugs
specifically target the prostaglandin pathway, reducing the gastrointestinal
side effects of the nonselective NSAIDs. But after Vioxx was pulled from the
market last year due to cardiovascular risks, the researchers switched to
using two nonselective NSAIDs, ibuprofen and naproxen, so that the controversy
over selective NSAIDs wouldn’t cast a shadow over their work.

The group saw a 25 percent reduction in prostate cell growth using only
calcitriol, and approximately the same reduction using only ibuprofen and
naproxen. But when they combined calcitriol and an NSAID, they saw up to a 70
percent reduction. This result was obtained using from one-half to one-tenth
the concentration required for either of the drugs used alone.

The group’s findings are the basis of a new clinical trial Feldman has begun
with oncologist Sandy Srinivas, MD, assistant professor of medicine. Men who
have been treated for prostate cancer, but who are experiencing a recurrence,
take naproxen twice a day combined with a high, once-weekly dose of calcitrol.
Weekly administration of calcitriol avoids a pitfall of earlier studies that
used daily dosing: too much calcium in the blood, a condition called
hypercalcemia, which can lead to kidney stones.

Feldman’s group uses calcitriol for both the cell culture studies and the
clinical trial to ensure that enough of the active form of vitamin D is in the
patients to be effective. Feldman emphasized that calcitriol is available by
prescription only. “We don't want the patient to think that if they take
over-the-counter vitamin D, it will work in the same way,” he said.

Staff research scientist Aruna Krishnan, PhD, research associate Srilatha
Swami, PhD, and urology postdoctoral scholar Larisa Nonn, PhD, also
contributed to this work, which was funded by grants from the National
Institutes of Health and the Department of Defense.

ancer than either treatment on its own.  This trial finished recruiting
patients in August 2005, so we are now waiting for the results.

There is also research into different ways of giving radiotherapy.  In
conformal radiotherapy a computer is used to 'shape' the radiotherapy beams to
a more exact shape of your prostate.  The idea is to cut down on the amount of
healthy body tissue that receives radiation.  

In September 2002 NICE issued guidelines for the treatment of prostate cancer
that said conformal radiotherapy was the best way to give radiotherapy for
prostate cancer and should be available to patients.  It can lower the number
of men who have long term side effects of straining and bleeding from the back
passage (proctitis) after radiotherapy for prostate cancer.  We have included
it here because conformal radiotherapy is still being investigated in clinical
trials.  

Although doctors know conformal radiotherapy can reduce side effects, we don't
know yet whether it could be better at controlling prostate cancer.  Doctors
may be able to give higher doses of radiation to the prostate because the
treatment is better targeted.  The hope is that this will give a higher chance
of cure.  A Medical Research Council trial of high dose conformal radiotherapy
finished recruiting in December 2001.  The researchers are now monitoring the
men that took part in this trial.  It will be another few years before we know
whether the high dose treatment was better at stopping the cancer from coming
back.  

Studies are taking place in the UK of a type of conformal radiotherapy called
intensity modulated radiotherapy (IMRT).  Like conformal radiotherapy, IMRT
shapes the radiation beams to closely fit the area where the cancer is. But it
also alters the dose of radiotherapy depending on the thickness of the body
tissue. So the whole area treated  receives the same dose. Researchers want to
find out how IMRT compares to standard radiotherapy.

Researchers are also looking at different ways of giving the total dose of
radiotherapy for men with prostate cancer.  A trial is underway that aims to
find out if giving a higher dose of radiotherapy per fraction, but fewer
fractions works as well as standard radiotherapy.  The researchers also want
to find out what the side effects are.  All men on this trial will have IMRT.  
There is information about this trial on the CancerHelp UK trials database.  
You can find it by clicking on the clinical trials button to the left of your
screen and picking 'prostate' from the drop down menu of cancer types.

Hormone therapy
Cancer of the prostate depends on the male hormone testosterone its growth.  
If the amount of testosterone in the body is reduced, it is possible to slow
down or shrink the tumour. Sometimes the cancer symptoms disappear completely.
There is information here about

New hormone therapies                  
Timing of hormone therapy  
Hormone therapy in combination with other treatments
New hormone therapies
Doctors are continuously looking for new hormone therapies to treat prostate
cancer.  Many of the current hormone drugs cause a rise in testosterone when
they are first taken. So prostate cancer symptoms tend to get worse before
they improve. A drug called abarelix does not seem to do this. Research so
far, shows that abarelix works more quickly on prostate cancer and does not
seem to cause the initial rise in testosterone levels that other standard
hormone drugs do. There are other similar agents also being tested such as
degarelix, ganirelix and cetrorelix.

In 2003 a small pilot study looked at HRT patches to treat men with advanced
prostate cancer. The researchers reported that all the men in the study who
were treated with HRT patches felt that they had an improvement in their
quality of life. But this was only one small study so  larger, randomised,
controlled clinical trials are needed before we know more about the side
effects men get when on hormone patches. Researchers are planning one such
trial which will compare an oestrogen patch with standard hormone treatment.

Hormone therapy timing
There are clinical trials looking into the timing of hormone therapy.  Some
doctors believe that intermittent hormone therapy is better at controlling
prostate cancer than continuous hormone therapy.  This means having hormone
therapy for 6 months, then having a break for a while and then having it for
another 6 months.  A trial looking at intermittent hormone therapy for
localised prostate cancer finished recruiting in February 2006.  Another, for
advanced prostate cancer is still open and recruiting patients.  There is more
information about this trial (called EORTC 30985) on the CancerHelp UK
clinical trials database.  You can find this and other prostate cancer trials
by clicking on the clinical trials button to the left of your screen and
picking 'prostate' from the drop down menu of cancer types.

A trial in the UK is looking at using the hormone therapy diethylstilbestrol
with steroids and aspirin for prostate cancer that has spread.  The
researchers are particularly looking at when to give the hormone therapy – at
the start of treatment or at a later stage.  This trial is also listed on our
CancerHelp UK clinical trials database under 'prostate' trials.

Hormone therapy in combination with other treatments
Hormone treatment often works well for prostate cancer that has spread outside
the prostate gland.  But doctors think that using it with other treatments
could work better.  A trial called STAMPEDE is studying the combination of
hormone therapy with chemotherapy, bisphosphonates or celecoxib for men who
have prostate cancer that has grown outside the prostate gland, or started to
grow again after treatment with radiotherapy or surgery.  While this trial is
recruiting it will be listed on the CancerHelp UK trials database.  You can
find this and other prostate cancer trials by clicking on the clinical trials
button to the left of your screen and picking 'prostate' from the drop down
menu of cancer types.

Chemotherapy
In the past chemotherapy drugs have not been widely used to treat prostate
cancer. We thought prostate cancer didn't respond very well to chemotherapy.
But recent clinical trials using some well known drugs -  mitoxantrone
(mitozantrone) and docetaxel (Taxotere) - have proved this wrong. Chemotherapy
is most likely to be used for prostate cancer when the cancer has spread and
has stopped responding to hormone therapy.

Results of 2 phase 3 trials have been published recently. They both showed
that docetaxel was better than mitoxantrone for prostate cancer that has
continued to grow despite hormone therapy (hormone refractory prostate
cancer).  There was a small increase in survival time for the docetaxel
groups.  Docetaxel was also more likely to improve quality of life by reducing
bone pain and other cancer symptoms.  In one trial docetaxel was combined with
estramustine. In the other it was combined with prednisolone.

Docetaxel is now licensed across Europe as a treatment for prostate cancer
that is no longer responding to hormone treatment.  But it has not yet been
approved by NICE (the National Institute for Health and Clinical Excellence).  
So it is not currently available as a standard treatment on the NHS in the UK.
But do speak to your own specialist if you'd like to know more.  It may be
possible for your doctor to prescribe it for you.  NICE are due to consider
whether docetaxel use should be recommended as an NHS treatment for advanced
prostate cancer in the near future.

Doctors continue to study different combinations of chemotherapy drugs,
different doses, or different sequences in which they are given. The aim of
this type of research is to find more effective ways of treating prostate
cancer with chemotherapy.

New bisphosphonates
Bone pain and fractures can be a problem in advanced prostate cancer.  This is
because the prostate cancer has spread to the bones and the growth of the
cancer cells leads to the destruction of bone tissue.  Bisphosphonates are
mainly used to help prevent or control bone thinning (osteoporosis).  But they
may also help to

Control bone pain and in turn lower the amount of painkillers you need to take
                           
Slow down the damage caused to bone from bone secondaries                      
     
Prevent or delay damage to bone leading to fractures or pressure on your
spinal cord from damaged bones in your spine
There are clinical trials underway that are looking into the most effective
bisphosphonate to use and also when to use it.  A Cancer Research UK supported
trial is comparing treatment with bisphosphonates to radiotherapy to see which
is best at controlling pain from bone secondaries.  This is called the RIB
trial.  

Another trial is looking at the bisphosphonate drug zoledronic acid (Zometa)
in combination with chemotherapy and the internal radiotherapy strontium 89.  
This trial is called Trapeze.  The researchers want to find out how well these
treatments work together and what the side effects are.  You can find this and
other prostate cancer trials on our trials database by clicking on the
clinical trials button to the left of your screen and picking 'prostate' from
the drop down menu of cancer types.  

Cryotherapy (cryosurgery)
Cryotherapy (also called cryosurgery) is a way of killing cancer cells by
freezing them.  In the past cryotherapy was not used very much in the UK to
treat prostate cancer because research showed that cancer often came back and
it had quite severe side effects, with about 8 out of 10 men (80%) not being
able to have an erection (impotence) after treatment.  But cryosurgery is now
being used more as new techniques have improved the treatment and helped
reduce side effects.    

To have this treatment, a number of metal probes are put through the skin and
into the affected part of the prostate.  The probe contains liquid nitrogen,
which can freeze and destroy the cancer.  Local anaesthetic is usually used to
numb the prostate gland and surrounding area.  Even so, this treatment can be
painful.  You will need to have a catheter to drain your urine for a week or
so afterwards.  This treatment may be an option for men whose disease comes
back after radiotherapy treatment.

In May 2005 NICE (the National Institute for Health and Clinical Excellence)
issued guidance on cryotherapy for prostate cancer that has come back
(recurrent prostate cancer).  And in November 2005, they issued guidance for
cryotherapy for early prostate cancer, confined to the prostate gland.  They
say that it appears to be safe and effective but they don’t know if it helps
men to live longer or have a better quality of life.  So they say that your
doctor should discuss the risks and causes with you, and what other treatment
options you may have.  Doctors must also monitor  patients who have
cryotherapy so that  they can learn more about side effects and the long term
benefits or drawbacks.   You will sign a consent form to say that all these
things have been explained to you.  There is a more detailed 'question and
answer' on cryotherapy for prostate cancer in the prostate cancer question and
anwer section of CancerHelp UK.

High frequency ultrasound (HIFU)
This treatment is being investigated as a possible alternative to surgery for
localised prostate cancers.  Doctors have used it for cancer that has just
been diagnosed, or for cancer that has come back in the prostate after earlier
treatment.

When high frequency sound waves are concentrated on body tissues, they heat up
and die.  To use this as a cancer treatment, the specialist targets the area
containing the cancer.  Because the prostate is situated deep within the
pelvis, you have HIFU for prostate cancer by putting an ultrasound probe into
your back passage (rectum).  From that position, the ultrasound can direct
beams more accurately at the prostate.  Doctors call these ‘transrectal
probes’.  Results from trials so far show that HIFU may be as successful in
treating prostate cancer as treatment with radical prostatectomy or
radiotherapy.  But we also have to be sure that the long term results will be
as good as surgery or radiotherapy.  The treatment hasn't been around long
enough for us to know that yet.

In March 2005, NICE (The National Institute for Health and Clinical
Excellence) issued guidance for doctors on HIFU for prostate cancer.  They say
that this treatment is safe enough, and works well enough, for doctors to
provide it on the NHS, providing men know

What is involved in having the treatment              
That we don't know everything about side effects yet              
That we don't fully understand how long term effects of HIFU compare to other
treatments              
What other treatment options they have
Doctors must also monitor all the patients who have HIFU so that we can learn
more about side effects and long term benefits or drawbacks.  You will sign a
consent form to say that all these things have been explained to you before
you have the treatment.  NICE say HIFU can be used for early prostate cancer
or for prostate cancer that has come back in the prostate after other
treatment (this is sometimes called salvage treatment).  You can download the
advice on HIFU from NICE on this link.

There is a clinical trial looking at HIFU for early stage prostate cancer
currently running in Stockport, near Manchester. They finished recruiting
patients into a pilot study in July 2005, and we are now waiting for the
results. If the results are promising, they will go on to recruit more
patients in a phase 2 trial. They recruited patients who

Have cancer that is contained within the prostate (T1 or T2 ) and hasn't
spread to another part of the body, and                    
Are newly diagnosed with prostate cancer and cannot have radiotherapy, or      
             
Have prostate cancer that has come back after radiotherapy
Another trial for prostate cancer is open in Oxford and London, this is part
of a larger European study.  This is also recruiting men who have cancer that
is contained within the prostate. There is information about this trial on our
clinical trials database. To find the information, click the blue clinical
trials button to the left of your screen and select 'prostate' from the drop
down menu of cancer types.

Photo-dynamic therapy
This means treatment using light.  It has been tried for other types of
cancer, mostly skin cancers or cancers of the head and neck.   There is some
patient research using it for prostate cancers that have come back after
radiotherapy.  To have this treatment, you have to take a drug that makes your
body cells very sensitive to light.  Then a strong light is shone directly
onto the cancer.  The light activates the drug inside the cells and they are
killed.  This is not an easy treatment to have.  You have to stay in dim light
for days or weeks before and after you have the treatment.  So far it has only
been tried for a few patients with prostate cancer.  But it did seem to help
some of them.   About half had a decrease in PSA levels.  And about a third
had no trace of cancer when they were tested later.  These were small numbers
though and more research has to be done.

In the UK PDT is being investigated in a trial for men with untreated,
localised prostate cancer. The men on this trial have decided to have active
monitoring of their disease. Researchers want to find out how well PDT works
for these men, and what the side effects are.  There is information about this
trial on our clinical trials database. To find the information, click the blue
clinical trials button to the left of your screen and select 'prostate' from
the drop down menu of cancer types.

Vaccine therapy
Vaccines are a type of immunotherapy.  It is still early days in prostate
cancer vaccine research.  Vaccines are available only in clinical trials as
this type of treatment is still highly experimental.

Cancer vaccines are designed to try to stimulate the body's own immune system
to fight cancer.  There are different ways to make vaccines.  Some can be used
by anyone with prostate cancer, while others are made specifically for each
patient.  The personalised vaccines are made by taking cells called dendritic
cells out of a patient's blood and mixing them with their own prostate cancer
cells.  The idea is that the dendritic cells in the vaccine will stimulate
other cells in the immune system to recognise and attack the prostate cancer
cells in the body.

Other types of prostate cancer vaccines in trial use viruses that have been
modified in the laboratory to contain prostate specific antigen (PSA).  When
the virus injection is given, the immune system reacts to the virus.  It
becomes sensitive to PSA and kills the prostate cancer cells that contain it.

There are several centres working on prostate vaccines. You should ask your
specialist if you are interested in finding out whether you can have vaccine
treatment within a clinical trial.  While it is still recruiting, there is DNA
vaccine trial for prostate cancer on the CancerHelp UK trials database.  You
can find this and other prostate cancer trials by following the link or
clicking on the clinical trials button to the left of your screen and picking
'prostate' from the drop down menu of cancer types.  

This is still all early stage research – phase 1 and 2 trials.  That means
that the research is looking at the safety of these new types of treatment or
testing whether they are likely to work against prostate cancer.  Early phase
trials tend to be quite short running – weeks or months.  So if you are
interested in vaccine trials, it may be worth checking the trials database
from time to time to see what if any new trials have opened.  

Gene therapy
This is one of the newer approaches to cancer treatment and is in the very
early stages of clinical trials.  Cancer cells carry abnormal genes.  If
researchers can get copies of the normal genes inside the cells to replace the
abnormal genes, they may be able to use this to treat the cancer.  

One gene that is often abnormal in cancer cells is the P53 gene.  This gene
usually tells cells that are old and damaged to self destruct.  Scientists
call this self destruction 'apoptosis'.  Cancer cells don't self destruct
because they have an abnormal p53 gene.  This is one reason why they can go on
reproducing even with damaged genes.  

Gene therapy is in the very early research stages and we don't know if it will
work yet.  A UK trial looking at gene therapy for early stage prostate cancer
closed in October 2004. Another for more advanced prostate cancer closed in
September 2005. We are now waiting for the results of both these trials. Like
other gene therapy research, this study is investigating how to get the new
genes inside the cancer cells.  

Endothelin blockers
These are new drugs that may block the growth of cancer cells.  They work by
blocking growth receptors called endothelin receptors.  You may hear these
drugs called endothelin blockers or endothelin receptor agonists.  

There have been some early results from trials showing that endothelin
blockers may be able to slow down the growth of cancer in the bone and delay
the symptoms of secondary bone cancer when given to patients with advanced
prostate cancer.  Researchers have been studying several endothelin blockers.
Trials of drugs called Atrasentan and YM598 have now finished recruiting
patients.  And it will be some years before we know the full results.

Another new endothelin blocker is a drug called ZD4054. It is being studied in
a trial for men whose cancer has spread to their bones. There is more
information about this trial on our clinical trials database . Either follow
the link or click on the blue button to the left of your screen. Then choose
prostate from the drop down menu of cancer types.

Blood supply and prostate cancer
'Angiogenesis' means the growth of new blood vessels. Cancers need to grow
their own blood vessels as they get bigger.  Without its own blood supply, a
cancer cannot continue to grow.  There is information here about thalidomide
and COX-2 inhibitors.

Thalidomide
Thalidomide is an anti-angiogenic drug.  This is a drug that blocks the
development of new blood vessels. Trials are testing thalidomide as a prostate
cancer treatment.  Trials in the UK have now recruited all the patients they
need and the researchers will be following the progress of those who took part
for the next few years.  Early results show that the thalidomide did lower PSA
in a few patients.  But there were side effects that were severe enough to
make people stop the treatment.  Thalidomide can cause constipation,
drowsiness, dizziness, rash and pins and needles and numbness in fingers and
toes.

COX-2 (COX-II) inhibitors  
COX-2 inhibitors are from the group of drugs called non steroidal
anti-inflammatory drugs (NSAIDs). COX-2 inhibitors are already used for other
medical conditions such as arthritis, and for the prevention of bowel cancer  
for certain people at 'high risk' of developing it. They stop an enzyme called
cyclo-oxygenase working. The enzyme COX-2 stimulates the production of a
growth factor called vascular endothelial growth factor, or VEGF. VEGF helps
cancers make their own blood vessels so they have a good enough blood supply
to keep growing.

Researchers think a COX-2 inhibitor called celecoxib (Celebrex) may be useful
in the future for treating prostate cancer. If celecoxib can reduce the amount
of VEGF in prostate cancer cells it will mean that the cancer will not be able
to grow. Doctors think COX-2 could also have a role in the prevention of
prostate cancer. But more research is need before this can be known for sure.  
A recent trial in the UK looked at celecoxib before surgery for prostate
cancer. The researchers wanted to see what effect it has on normal cells and
prostate cancer cells. It has only recently closed so we don't know what the
results are yet.

These articles haven't made me want to rush out for
a prescription for Celebrex, but they have reinforced
my intention to continue taking ibuprofen, which has at
least some of the same effects as the pure Cox-2
inhibitors.

I have been taking small doses of ibuprofen every day
because of its apparent ability to slow the onset of
Alzheimer's Disease - which I think I fear even more than
cancer.  It's nice to know that I'm may also be getting
some anti-cancer benefit from it.

   Alan

My positive biop came just over two years ago.
Doctor wanted to do a radical
My psa was 5.6
Nothing on a digital
12 needle bio showed one core with 5 pct.
No parinoia or fear at all.
I went off testosterone injections and started taking zinc and was already on
celebrex for herniated disks.
cut way back on animal fats.
i was put on watch and wait.
just finished year two biop...12 small needles.
doctor powsang from moffett called and left a msg that he has good news.
do not have details yet.
suspect no pca found this time but needle could have missed the spot
so I cant go back on testosterone and must stay watchful waiting.
.have had digital every 4 months and never had any thing felt.
this biop was small needle as i am on blood thinners plavix for heart problems
and cant go off it.  last psa was 7.2 so careful watch is appropriate.

will report biop findings in a week or so.
hope noting found.
wish me luck.

the celebrex reduces inflamation and theory is that it can affect the growth
of prostate and other cancers... see reorts attached.  interesting to say the
least.  does anyone else have a similar story?

rgds, lyman