>>Yale Researchers Find Phenoxodiol Restores Sensitivity to Chemotherapy in Some Women With Ovarian, Fallopian Tube or Primary Peritoneal Cancer, in Interim Report on a Phase II Study
Wednesday March 29, 8:28 am ET
WASHINGTON and SYDNEY, Australia, March 29 /PRNewswire-FirstCall/ -- Phenoxodiol, an investigational anti-cancer drug that is being studied by leading researchers at Yale, has been found to be active and to restore platinum drug sensitivity to some patients who have shown prior resistance to platinum-based chemotherapy agents. The data were presented at the Annual Meeting on Women's Cancer organized by the Society of Gynecologic Oncology.
The study is designed to test the ability of phenoxodiol to reverse the resistance that develops in most ovarian cancers to standard chemotherapy. The study was conducted at Yale - New Haven Hospital, Conn., USA, as well as at the Royal Women's Hospital, Melbourne, Australia.
"Phenoxodiol was developed to overcome this chemical resistance within tumor cells, thereby allowing standard anti-cancer drugs such as cisplatin, carboplatin and paclitaxel to continue to work in this aggressive form of cancer," said Michael Kelly, MD, Fellow at Yale University School of Medicine. "What we are seeing with phenoxodiol is an encouragingly high proportion of tumors either shrinking or stabilizing with standard drugs, when we know that the tumor is unlikely to respond to those standard drugs alone."
Patients with tumor shrinkage or stabilized tumors are collectively known as having controlled disease. The particular relevance of this outcome is that the FDA's current draft guidance document suggests that prolonged survival of patients is a more appropriate clinical endpoint than tumor response alone. That is, the length of time that the tumor fails to grow, may be more meaningful in terms of patient survival than the incidence of tumor response on its own.
The Yale researchers reported that 74 percent of patients with late-stage, platinum-resistant tumors who received the phenoxodiol and cisplatin combination showed evidence of a change in tumor growth by way of either tumor shrinkage or no increase in tumor size.
The ability of phenoxodiol to effect patient survival and progression-free survival is to be tested in a pivotal study known as the OVATURE study, in which phenoxodiol will be used in combination with carboplatin in patients with tumors that are refractory or resistant to platinum therapy.
About ovarian cancer
Ovarian cancer is the gynecologic cancer most likely to lead to death among women in the U.S., due in part to the eventual development of resistance of the tumor to chemotherapy. In approximately 10 to 15 percent of patients, the tumors show a high level of resistance to initial, standard therapy. In the remaining 85 to 90 percent of initial responders, the tumors eventually re-grow in most of these patients due to the selection of chemo-resistant tumor cells. Ultimately these tumors become completely resistant to standard drugs.
The research was conducted at Yale in collaboration with co-authors Gil Mor, M.D., Lisa Baker, Jessica McAlpine, Masoud Azodi, Peter Schwartz, M.D., and Thomas Rutherford, M.D. Participants were also recruited from the Royal Women's Hospital, Melbourne, Australia. Additional research was conducted at Royal Women's Hospital, Melbourne, Australia; Marshall Edwards, Inc., Sydney, Australia; and at Ohio State University, Columbus, Ohio.
About phenoxodiol
Phenoxodiol is an investigational drug and, as such, is not marketed in the United States. Phenoxodiol was granted fast-track status by the FDA in November 2004 for its intended use in women with ovarian cancer.
Phenoxodiol is a novel acting drug that inhibits key pro-survival signaling pathways generated by the sphingomyelin pathway. These pathways (eg. sphingosine-1-phosphate) are over-active in tumor cells, and their inhibition by phenoxodiol leads to the prevention of production of key pro- survival proteins such as XIAP. XIAP, an anti-apoptotic protein, prevents cell death by blocking signals coming from the death receptors on the cell surface. Removal of such anti-apoptotic proteins restores the ability of tumor cells to undergo apoptosis in response to chemotherapy.
The putative primary molecular target of phenoxodiol is a family of proteins expressed on the surface of tumor cells, but not on non-tumor cells. The restriction of expression of that family of proteins to tumor cells is thought to account for the high specificity of phenoxodiol.
Phenoxodiol is able to kill ovarian cancer cells that are highly resistant to standard anti-cancer drugs, as well as being able to restore sensitivity in these cells to standard anti-cancer drugs such as taxanes. These findings have been borne out in recent clinical results showing that some women who have stopped responding to taxane and platinum drugs had disease regression when phenoxodiol was given in combination with their chemotherapy.<<
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