Phenoxodiol shows very interesting activity in a number of tumortypes when
combined with standard chemotherapy for that tumor. It does not seem to
influence toxicity of those drugs. The synergy with hormonal therapy in
prostate cancer is also promising. It is going to be tested in earlier
stages and probably also in combination with Taxanes in prostate cancer.
Phenoxodiol Delays Progression in Hormone Refractory Prostate Cancer,

No side-effects, study says
"Designed to end after 24 weeks of treatment, the trial has been
extended to 90 weeks so far because of the unexpected extended survival
in some patients. Patients have been able to remain on phenoxodiol for
this extended time without any evidence of drug-related toxicity."

November 17, 2005. - Phenoxodiol is an oral drug designed to treat
late-stage, chemo-resistant prostate, ovarian and renal cancers.
Marshall Edwards, Inc., the company that makes phenoxodiol, has called
it a synthetic analog (i.e. mimic) of genistein, which is a chemical
found in soy.

Phenoxodiol is in clinical trials in the US and Australia to see if it
has potential on its own (as a monotherapy) and in combination with
standard anti-cancer drugs. For patients who are responding to a
chemotherapy, the aim is to boost the overall response. For patients
whose cancer has stopped responding to chemotherapies, the aim is to
restore sensitivity to those drugs.

A study reported today at a conference in Philadelphia says the drug has
benefit for patients with advanced hormone refractory prostate cancer
and has no side-effects.

The anti-tumor effect in this Phase Ib/IIa trial was dose-dependent --
only patients receiving higher doses showed a good response.

The trial was designed to end after 24 weeks of treatment, but was
extended to the current 90 weeks because of the unexpected extended
survival in some patients. Patients have been able to remain on
phenoxodiol for this extended time without any evidence of drug-related
toxicity.

There were 4 serious adverse events during the trial, but according to
the company none of these were connected with phenoxodiol. (One of the
hazards of early stage clinical trials is that "non-drug related adverse
events" may arise if patients are assigned to what turns out to be a
weak or ineffective dose, leaving them in effect in a treatment gap that
allows worsening of their cancer.)

At higher doses, 7 out of 10 patients got more than 6 months benefit

In this trial men with metastatic, hormone-refractory prostate cancer
received various doses (20, 80, 200 and 400 mg) of phenoxodiol to
establish what level of anti-cancer effect the oral dosage form of this
drug would provide and whether there was a dose-dependent effect.

The men took phenoxodiol in monthly treatment cycles with 3 doses daily
for 21 consecutive days followed by 7 days without treatment. The
original plan was to treat patients for a maximum of 6 treatment cycles.
Except for anti-androgen therapy being continued in those who were
receiving it pre-trial, phenoxodiol was the only treatment. The age of
the 26 subjects studied ranged from 55 to 85, the Gleason score was mean
8.04 (range 6-9), and the mean baseline PSA level was 56.3 pg/ml.

Response to therapy in these patients was measured by
PSA response (a decline in PSA level compared to baseline of at least 50
percent)
PSA doubling time (time for the baseline PSA level to double)
and time to progression (length of time that patients remained on
phenoxodiol based on PSA levels and clinical assessment).

How it works

Cells, like water softeners, use ion exchange pumps. Phenoxodiol aims to
bring about cancer cell suicide (apoptosis) and necrosis (decay) by
targeting the tumor cell's cation (positive ion) excretion pump. If it
works, this disrupts the cancer cells' redox potential by slowing
signals along the sphingosine-1-phosphate and Akt signalimg pathways.
Sphingosine 1-phosphate (S1P) is a cell signaling molecule that helps
cells, including cancer cells, to grow.

Phenoxodial aims to tame tumor growth by disrupting signals from S1P and
related molecule, Akt.

For a demo of the AKt signaling pathway visit BioCarta.

"The two highest dosages of phenoxodiol provided a significant
anti-tumor response in a disease that is normally unresponsive to
treatment in its late stages," says Robert Davies, MD, lead investigator
of the study and urologist at Sir Charles Gairdner Hospital in Perth,
Australia. "We found that the PSA level, an indicator of the level of
cancer, decreased. We also saw a clinical response that was prolonged in
some patients."

Combining the data from the two lowest dosages (12 patients) and the two
highest dosages (14 patients), the number of patients still on therapy
after 6 months increased from 1 out of 12 (8.5 percent) to 10 out of 14
(71.4 percent), and the mean time to progression (length of time
patients were deemed to be deriving a benefit from therapy) increased
from 15 weeks to 47 weeks. This latter figure does not take into account
four patients who remain on therapy after 42, 74, 82 and 90 weeks.

In terms of PSA levels, there were no PSA responses in the two lowest
dosage groups, but 3 of the 14 in the two highest dosage groups
experienced a PSA level reduction of 50 percent or greater from
baseline.

The PSA doubling time increased from a mean 18 weeks to 43 weeks, not
including the 3 of 14 patients who remain on phenoxodiol therapy and
whose PSA levels have yet to double. While it was not possible to
measure tumor size in this study, an increase in PSA doubling time is
generally regarded as reflecting a tumor response.

"The long-term anti-tumor effects and safety demonstrated in this study
are very encouraging developments," said Graham Kelly, Ph.D, Chairman of
Marshall Edwards, Inc., the company which makes this drug.

A Californian oncologist who referred two patients to the trial agrees
that the results are good news, and may impact the way prostate cancer
is treated.

"Phenoxodiol represents a unique new class drugs for men with prostate
cancer," says Steven Tucker, MD, Director of Prostate and Genitourinary
Oncology at The Angeles Clinic & Research Institute in Los Angeles.

"If the clinical benefit seen in these refractory patients can be
extended into an earlier disease state, we may be looking at a paradigm
shift in the management of advanced prostate cancer," says Dr. Tucker,
who is also an Assistant Clinical Professor of Medicine at the UCLA
School of Medicine.

Professor Kelly said that the next stage of development of phenoxodiol
for prostate cancer would be to try it on patients who have failed to
respond to both hormone therapy and docetaxel (Taxotere) therapy.
"On the basis of this data, we would expect that phenoxodiol alone would
offer these patients a significant survival benefit, but we also will be
interested in testing the ability of phenoxodiol to restore sensitivity
to docetaxel in these end-stage patients," Professor Kelly added.

This next study will be conducted in the U.S. and is planned to commence
enrollment in 2006.

These study results were presented November 17, 2005 in a poster session
(.pdf download) at the International Conference on Molecular Targets and
Cancer Therapeutics in Philadelphia. The meeting is sponsored by the
American Association of Cancer Researchers (AACR), the National Cancer
Institute (NCI), and the European Organization for Research and
Treatment of Cancer (EORTC).

Phenoxodiol is an investigational drug and, as such, is not marketed in
the US.
More information about phenoxodiol can be found at
http://www.phenoxodiol.com
by J. Strax November 17, 2005.

knowledge is power - growing old is mandatory - growing wise is optional
"Many more men die with prostate cancer than of it. Growing old is
invariably fatal. Prostate cancer is only sometimes so."
http://community.webtv.net/PALMER_ENT/doc

Phenoxodiol Delays Progression in Hormone Refractory Prostate Cancer,

***********

It seems that they have already obtained from fda, fast track status for its
intended use in patients with hormone-refractory prostate cancer.
http://www.novogen.com/news/news0501.cfm?mainsection=05&subsection=01&newsid=171
Regards