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Phenoxodiol - What Is It? ....Somebody Is Bound To Ask You.
(July 2005)
ANSWER: Phenoxodiol is an isoflavone, a more stable
synthetic derivative of its cousin genistein, the ingredient of interest
in soy products, much studied for its beneficial effect on prostate
cancer.
The interest in phenoxodiol results from the November 2004
presentation at the American Association of Cancer Research conference on
Translational and Clinical Advances in Prostate Cancer of an Australian
Phase Ib/IIa study of this agent in 19 men with late stage, metastatic
prostate cancer. At doses of 200 mg and 400 mg q 8 hrs 2 of 4 and 3 of 4
men, respectively, showed no evidence of disease progression at 6 months,
and the PSA values in 5 of 6 were below baseline at 6 months. This very
encouraging result raised the possibility that phenoxodiol could slow the
progression of prostate cancer - and accomplish this with little or no
toxicity.
Considerable investigation has been directed at
understanding the phenoxodial’s mechanism of action, and these findings
have provided a sound basic science foundation supporting the expectation
that this drug will be clinically useful. In Cancer Research, April 2005,
Aguero et al. reported that phenoxodiol induced an inhibitor of cell cycle
progression, p21, and achieved its antiproliferative effect by promoting
cell cycle arrest at the G1-S phase checkpoint. Other researches have also
identified an anti-proliferative effect resulting from interference with a
vital cancer cell membrane enzyme and thereby promoting apoptoses. And a
report at ASCO 2005 found that phenoxodiol induced increased intracellular
levels of ceremide, also a promoter of apopotosis. These researchers
concluded “The cytotoxicity of PXD [phenoxodiol] in highly drug-resistant
tumor cells suggests its clinical utility in patients with advanced,
chemorefractory cancer”.
Researchers at Yale have conducted basic science studies in
ovarian cancer and determined that phenoxodiol is a potent chemosensitizer
of docetaxel and can restore drug sensitivity to doxetaxel-resistant
cells. One application of this finding would allow a doxetaxel dose
reduction when combined with phenoxodiol. Phenoxodiol is currently under
active clinical investigation in ovarian cancer.
Although the drug is not currently available, on the basis
of the November report, the FDA has granted the Marshall Edwards
Corporation fast track status for wider investigations of phenoxodial in
clinical studies of patients with hormone refractory prostate cancer.
A Phase IIB/IIIA multi-center international, clinical trial
of phenoxodiol at 400mg q 8 hrs for men with HRPC is planned titled
“COMPACT”, Comparison of Phenoxodiol Against Conventional Therapy. A
company spokesman has indicated that “the COMPACT study is being
formulated with a view to commencing later in 2005. It will be conducted
in patients with hormone-refractory, doxetaxel-refractory patients, with
phenoxodiol being assessed for its ability to reverse chemo-resistance to
doxetaxel.”
Bottom Line:
Encouraging early results suggest clinical usefulness for the newly
developed drug, phenoxodiol.
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