Researchers from Yale University’s School of Medicine reported today a further update on results from a clinical study in women with early-stage cancer of the cervix and vagina. The data were presented today at the international conference on molecular targets and cancer therapeutics 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 data, presented by Yale researchers Drs. Masoud Azodi, Peter Schwartz, Michael Kelly, Thomas Rutherford and Gil Mor at a meeting of the American Association for Cancer Research in Philadelphia, indicates continuing confidence that the experimental drug phenoxodiol has the potential to change management options for this highly aggressive gynecological cancer.
The study has so far recruited 16 women with squamous cell carcinoma of the cervix, vagina or vulva.
Phenoxodiol was administered 8-hourly for 21 to 28 days between their first diagnosis and surgical resection, the current first line strategy to manage this disease. To date 14 patients have been evaluated of whom 6 received 50 mg phenoxodiol per dose and 8 received 200 mg per dose. The tumor responses were assessed for change in size by the RECIST method.
In the 50 mg dose 5 of 6 patients had stable disease at the time of surgical resection whereas in the 200 mg dose group all 8 patients had stable disease at the time of resection.
Analysis of the resected tumor specimens indicated that the drug was concentrated in tumor tissues in levels which were greater than the levels in the blood of these patients and further that the drug was converted to a more active form by deconjugation within the tumor. The researchers observed that cervical cancer tissue may contain the necessary deconjugating enzymes (glucuronidase, sulfatase) that convert the conjugated form of the drug (the principal form of the drug in the blood) to the bio-active free form, and that the free form of phenoxodiol then accumulates in the tumor tissue. This suggests phenoxodiol is uniquely suited to treatment of this type of cancer.
No toxicity was observed in any patients even in the 200 mg dose stratum, indicating the high safety profile of the drug.
�This response rate of 92.8 percent in the low dose group and 100 percent in the high dose group, compared to an expectation of otherwise progressive disease, represents an outstanding result considering the relatively short time frame over which phenoxodiol could be administered in this study,� said Professor Graham Kelly, Phenoxodiol Program Manager for Marshall Edwards, Inc.
�The 28-day period of treatment in this study is a relatively short time to expect to see a change in tumor progression in these patients,� Professor Kelly said �These data with cervical cancer provide evidence that orally-administered phenoxodiol has a significant anti-tumor effect, particularly in the case of squamous cell carcinomas, which are relatively insensitive to standard anti-cancer drugs.�
One of the Yale researchers, Dr. Mor, said �We are confident that these results indicate that phenoxodiol demonstrates a promising new opportunity in the management of this serious cancer experienced by many women.�
The study will continue to recruit additional patients to enable an evaluation of phenoxodiol at the higher dose stratum of 400 mg. per dose, and further studies will be performed on all resected tumor tissues to measure changes in cell proliferation activity at the microscopic level.
Phenoxodiol is an investigational drug and, as such, is not marketed in the United States. Phenoxodiol targets the plasma membrane sphingomyelin pathway, inhibiting the production of the pro-survival secondary messenger, sphingosine-1-phosphate (S-1-P), and in turn preventing the phosphorylation of the Akt signalling cascade and the formation of anti-apoptotic proteins.
Phenoxodiol is highly selective, with no detectable effect on the sphingomyelin pathway of non-tumor cells, accounting for the fact that phenoxodiol has no augmenting effect on the toxic effects of chemotoxic drugs on normal tissues.
Marshall Edwards, Inc., has licensed rights to bring phenoxodiol to market globally from its parent company, Novogen Limited. (ASX: NRT - Nasdaq: NVGN). Novogen is developing a range of therapeutics across the fields of oncology, cardiovascular disease and inflammatory diseases based on its phenolic drug technology platform.
More information about phenoxodiol can be found at http://www.phenoxodiol.com.
Revision date: July 7, 2011
Last revised: by Jorge P. Ribeiro, MD