Yale Cancer Centre announced that their researchers have begun recruiting 60 men for a clinical trial investigating an experimental new drug, oral phenoxodiol, as a potential first line therapy for prostate cancer. The study is funded by Yale Cancer Centre.

The clinical trial will be conducted at two sites, Yale Cancer Centre and the West Haven (Conn.) Veterans Administration Hospital. Yale Cancer Centre, a National Cancer Institute designated comprehensive cancer centre for over 30 years, is one of only 39 Centres in the nation and the only comprehensive centre in Southern New England.

"Promising data on phenoxodiol in prostate cancer piqued our interest," said Wm. Kevin Kelly, D.O., principle investigator for the trial, Associate Professor of Medicine and Associate Director of Clinical Investigations, Yale Cancer Centre. "This trial builds on the success of the previous prostate cancer trial with phenoxodiol. We will compare results from two types of prostate cancer patients - those with androgen independent disease and those with androgen dependent disease."

"If successful, development of phenoxodiol has the potential to provide a significant advancement in the treatment of prostate cancer," said Dr. Kelly.

All patients in the trial will receive 400 mg of oral phenoxodiol every 8 hours daily for 28 consecutive days (1 cycle). Treatment outcome will be evaluated after three cycles (12 weeks) of drug administration. Patients with progression of disease will be taken off study. Responding and stable disease patients will remain on study until disease progression or for a maximum of 12 cycles (approximately 12 months).

The primary endpoint of the trial is to determine the proportion of patients given phenoxodiol that have a 50 percent post-therapy prostate specific antigen (PSA) decline at 12 weeks in patients with: a) Androgen independent disease who are chemotherapy naïve (Group A); and b) Rising PSA after radical prostatectomy or radiotherapy that are androgen dependent (Group B)

The study will also evaluate safety of phenoxodiol in these patient populations. PSA is a protein produced by the cells of the prostate gland. PSA is present in small quantities in the serum of normal men, and is often elevated in the presence of prostate cancer and in other prostate disorders, a press release said.

A phase II clinical research study demonstrated a dose dependent anti-tumour effect by phenoxodiol in men with hormone refractory prostate cancer. The trial was designed to end after 24 weeks of treatment, but was extended to 90 weeks because of the unexpected prolongation of time to progression in some patients. No phenoxodiol-associated toxicities were reported in the study.

Researchers administered oral phenoxodiol to 26 patients at one of four dose levels, two subtherapeutic levels (20 mg and 80 mg three times daily) and two therapeutic levels (200 mg and 400 mg three times daily). Response to therapy was determined on the basis of PSA response, PSA doubling time, and time to progression.

While all 12 patients on the two lower dose levels of phenoxodiol showed disease progression within 6 months, nine (9) of the 14 patients on the higher doses of phenoxodiol remained progression-free on phenoxodiol after 6 months, indicating that disease progression occurred far more frequently in the lower subtherapeutic dose treatment group. In terms of PSA levels, the 12 patients in the two lower dose groups saw no improvement, while 3 of the 14 patients in the higher dose groups experienced a PSA level reduction of 50 percent or greater from baseline. The PSA doubling time increased from a mean of 18 weeks to 43 weeks, not including the 3 of 14 patients who remained on phenoxodiol beyond the term of the study.

According to the National Cancer Institute, prostate cancer is the second most common type of cancer among men in this country and the second leading cause of cancer death among men in the US. Only lung cancer is more common and kills more men. Prostate cancer will be diagnosed in more than 230,000 men each year, and approximately 28,000 men will die of the disease. At least forty percent of all men diagnosed with prostate cancer will at some point experience recurrent disease after definitive local therapy with radiation or prostatectomy. Most commonly, recurrence is manifested as a rising PSA and/or the development of metastatic disease.

Treatment options for early stage prostate cancer in androgen dependent pre-metastatic disease are limited. Patient options typically include "watchful waiting" or anti-androgen treatment, a form of chemical castration that is particularly unattractive for men who at this stage of disease are otherwise healthy.

Phenoxodiol is being developed by Marshall Edwards, Inc. as a therapy for late-stage, chemoresistant ovarian cancer and for prostate and cervical cancers. It is a novel-acting drug that inhibits key pro-survival signaling pathways operating via sphingosine-1-phosphate and Akt. Inhibition of these pathways leads to prevention of phosphorylation of key anti-apoptotic proteins such as XIAP. Loss of activity of these proteins induces cell death by apoptosis and restores the sensitivity of chemoresistant tumour cells to other chemotherapy drugs. The putative molecular target for phenoxodiol is a cancer-specific protein, accounting for the highly selective nature of the drug.

Phenoxodiol has received Fast Track status from the FDA to facilitate development as a therapy for recurrent ovarian and prostate cancers. Phenoxodiol is an investigational drug and, as such, is not commercially available. Under US law, a new drug cannot be marketed until it has been investigated in clinical trials and approved by FDA as being safe and effective for the intended use.

Phenoxodiol in combination with carboplatin is currently being studied in a multi-national phase III clinical trial called the OVATURE (OVArian Tumour REsponse) Trial, following positive findings of previous trials conducted in Australia and at Yale-New Haven Hospital. The OVATURE trial is taking place at up to 60 clinical sites in the United States, Europe, and Australia. Preliminary results from the trial are expected within 18 months.

Marshall Edwards, Inc. is majority owned by Novogen, an Australian biotechnology company that is specialising in the development of therapeutics based on a flavonoid technology platform. Novogen, based in Sydney, Australia, is developing a range of therapeutics across the fields of oncology, cardiovascular disease and inflammatory diseases.