Phenoxodiol Delays Tumor Progression in Advanced Prostate Cancer

 Press Release | 11.17.2005

A new study presented today at the International Conference on Molecular Targets and Cancer Therapeutics in Philadelphia shows that phenoxodiol significantly delays tumor progression in men suffering from late-stage hormone refractory prostate cancer. 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).

The anti-tumor effect in this Phase Ib/IIa trial was dose-dependent. The trial was designed to end after 24 weeks of treatment, but had to be 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 toxicity.

Researchers administered various doses (20, 80, 200 and 400 mg) of phenoxodiol to men with metastatic, hormone-refractory prostate cancer 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 phenoxodiol was administered in monthly treatment cycles comprised of 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 determined on the basis of 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).

"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. Professor Kelly presented the data on behalf of the investigators in the 12:30 - 2:30 pm poster session on Thursday, November 17, at the AACR-NCI-EORTC meeting.

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 use it in patients who have failed to respond to both hormone therapy and docetaxel 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.