Phenoxodiol Increases the Effectiveness of Docetaxel by at Least 100 Times
January 24 2005 - 8:44AM
PR Newswire (US)
Phenoxodiol Increases the Effectiveness of Docetaxel by at Least
100 Times Phenoxodiol Reverses Chemo-Resistance to Docetaxel in
Human Ovarian Cancer Cells WASHINGTON, Jan. 24
/PRNewswire-FirstCall/ -- The investigational anti- cancer drug,
phenoxodiol, considerably enhances the ability of the drug,
docetaxel (Taxotere(R), Sanofi-Aventis), to kill human ovarian
cancer cells in the laboratory. The findings are reported in the
current issue of Oncology Research (Vol. 14, pp. 567-578
http://tinyurl.com/49nvm). Phenoxodiol is being developed as a
chemo-sensitizer for standard chemotherapy agents such as taxanes
and platinums in ovarian cancer, and has been granted fast-track
status by the U.S. Food and Drug Administration based in part on
tumor measurements from radiographic examinations of women with
recurrent ovarian cancer who are participating in an ongoing
multi-center phase Ib/IIa study. Researchers from Yale University
School of Medicine used cancer cell lines established from patients
who had failed to respond to standard anti-cancer drugs. In the
laboratory, these cells are highly resistant to anti-cancer drugs,
including docetaxel. Phenoxodiol was able to restore sensitivity to
docetaxel in these resistant cells. The researchers also found that
the synergistic effect of phenoxodiol was so great that, when added
to the treatment mix, phenoxodiol allowed 1/100th of the amount of
docetaxel to be used as effectively as docetaxel alone on cells
previously found to be resistant to docetaxel. "These findings
offer two potential clinical outcomes. Either, phenoxodiol could be
used to considerably increase the response rate of patients to
docetaxel after they have become unresponsive to other standard
chemotherapies, or, phenoxodiol could lead to a dramatically
reduced amount of chemotherapy needed to achieve a clinical
response, which means that patients would be less likely to
experience the harmful side effects of chemotherapy," said Gil Mor,
M.D., Ph. D., associate professor, department of obstetrics,
gynecology and reproductive sciences, Yale University School of
Medicine. About Ovarian cancer Ovarian cancer is the most lethal
gynecological malignancy, and the fifth leading cause of cancer
related death in women in the United States. The American Cancer
Society estimates that there will be about 22,220 new cases of
ovarian cancer in this country in 2005. About 16,210 women will die
of the disease. One in 70 women will develop ovarian cancer and one
out of 100 women will die from this disease. This high mortality is
due mainly to the inability to detect early disease, with
approximately 80% of patients being diagnosed in advanced-staged
disease. However, even in those patients diagnosed with early-stage
disease, the five-year survival rate ranges from 60 to 90%
depending on the degree of tumor differentiation. The standard
first-line treatment of ovarian cancer is a platinum drug
(cisplatin or carboplatin) or a taxane (paclitaxel) or a mixture of
both. The response rate to these therapies in patients with
advanced disease generally is high, with 80%-90% of tumors
responding in the first instance. However, less than 10 - 15% of
these patients will remain in remission, with the remainder showing
re-growth of the tumor generally within 18-24 months. Most of these
relapsed cases are chemo-resistant and show only limited response
to second- and third-line agents such as docetaxel, gemcitabine,
doxorubicin and topotecan. The inherent resistance of 10-20% of
cases to first-line chemotherapy, and the development of resistance
in most cases of relapsed to subsequent therapy, represents the
major hurdle to effective management of late-stage ovarian cancer.
About Docetaxel Docetaxel is a taxane that is approved by the FDA
(i) for the treatment of women with early stage breast cancer,
locally advanced or metastatic breast cancer after failure of prior
platinum-based chemotherapy, (ii) for locally advanced or
metastatic breast cancer after anthracyline-based therapy, (iii) as
a first-line therapy for non-small cell lung cancer, (iv) as a
second-line therapy for non-small cell lung cancer following prior
treatment with cisplatin, and (v) for hormone-refractory prostate
cancer in combination with prednisone. Docetaxel is under
development as a chemotherapy for ovarian cancer. As a retrieval
therapy in patients with recurrent or persistent advanced ovarian
cancer, docetaxel faces a high level of drug resistance following
previous therapy with taxanes and other agents. About Phenoxodiol
Phenoxodiol was granted fast-track status by the FDA in November
2004 after receiving clinical data, including tumor measurements
based on radiographic examination, from the current Phase Ib/IIa
study. The study is being conducted at two sites (Yale-New Haven
Hospital, and Royal Women's Hospital, Melbourne, Australia) in
women with recurrent ovarian cancer which is either resistant or
refractory to taxane- and/or platinum-based drugs. Phenoxodiol is
an investigational drug that regulates signal transduction pathways
in cancer cells resulting in the break down of the intra-cellular
proteins -- XIAP (X-linked Inhibitor of Apoptosis Protein) and FLIP
(Fas Ligand Inhibitory Protein), which block the ability of the
cancer cell to undergo apoptosis via the death receptor
mechanism.(1) While these proteins play a vital role in preventing
unintentional cell death in healthy cells, they are over-expressed
in many forms of cancer, as well as being associated with the
development of resistance to anti-cancer drugs.(2) Phenoxodiol
works selectively on tumor cells because of its interaction with
the tumor-specific NADH oxidase, which is restricted to cancer
cells. Clinical trials to date have revealed no significant drug
related adverse side effects. Phenoxodiol is an investigational
drug and, as such, is not approved for marketing in the United
States. About Novogen Limited and Marshall Edwards, Inc.
Phenoxodiol has been developed by Novogen Limited (NASDAQ:NVGN), an
Australian biopharmaceutical company that is specializing in the
development of therapeutics based on the isoflavonoid ring
structure. Novogen, based in Sydney, Australia, is developing a
range of therapeutics across the fields of oncology, cardiovascular
disease and inflammatory diseases. Marshall Edwards, Inc.
(NASDAQ:MSHL) (LSE-AIM: MSH) has licensed from Novogen Limited the
rights to bring phenoxodiol to the global market. More information
on phenoxodiol and on the Novogen group of companies can be found
at http://www.marshalledwardsinc.com/ and http://www.novogen.com/.
Under U.S. law, a new drug cannot be marketed until it has been
investigated in clinical trials and approved by the FDA as being
safe and effective for the intended use. Statements included in
this press release that are not historical in nature are
"forward-looking statements" within the meaning of the "safe
harbor" provisions of the Private Securities Litigation Reform Act
of 1995. You should be aware that our actual results could differ
materially from those contained in the forward-looking statements,
which are based on management's current expectations and are
subject to a number of risks and uncertainties, including, but not
limited to, our failure to successfully commercialize our product
candidates; costs and delays in the development and/or FDA
approval, or the failure to obtain such approval, of our product
candidates; uncertainties in clinical trial results; our inability
to maintain or enter into, and the risks resulting from our
dependence upon, collaboration or contractual arrangements
necessary for the development, manufacture, commercialization,
marketing, sales and distribution of any products; competitive
factors; our inability to protect our patents or proprietary rights
and obtain necessary rights to third party patents and intellectual
property to operate our business; our inability to operate our
business without infringing the patents and proprietary rights of
others; general economic conditions; the failure of any products to
gain market acceptance; our inability to obtain any additional
required financing; technological changes; government regulation;
changes in industry practice; and one-time events. We do not intend
to update any of these factors or to publicly announce the results
of any revisions to these forward-looking statements. (1) Kamsteeg
M et al. Ibid. (2) Cheng JQ et al., 2002. Drug Resist Update 5,
131. DATASOURCE: Marshall Edwards, Inc. CONTACT: USA: David Sheon,
+1-202-518-6384, for Marshall Edwards, Inc.; or Australia: Dr.
Graham Kelly, Chairman of Marshall Edwards, Inc., +011 61 2 9878
0088 Web site: http://www.marshalledwardsinc.com/
http://www.novogen.com/ http://tinyurl.com/49nvm
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