Articles about new Ovarian Cancer drugs, treatment methods, research etc.

Ovarian Cancer Responds To Aspirin Derivative To Make Recurrent Cancer Cells Less Resistant To The Chemotherapy

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19 Feb 2006

A new study using ovarian cancer cell lines shows promise in treating the deadly disease by combining the chemotherapy drug cisplatin with an aspirin-like compound to make recurrent cancer cells less resistant to the chemotherapy.

The study appears online in the Proceedings of the National Academy of Sciences.

As a first course of treatment, ovarian cancer typically is treated with surgery followed by a regimen of the chemotherapy drug cisplatin. However, cisplatin is not an effective treatment when the ovarian cancer inevitably returns, says Periannan Kuppusamy, a professor of internal medicine at the Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute.

"Somehow the ovarian cancer cells adapt and become resistant to this drug," said Kuppusamy, lead author of the study. "Once treated with cisplatin, the ovarian cancer cells develop an abundance of thiols, which are a kind of cellular antioxidants that protect the cancer from the chemotherapy."

Kuppusamy wondered whether the abundance of thiols could somehow be used against the ovarian cancer cells. The study found that the nitric oxide released from the aspirin derivative NCX-4016 reacts with the cellular thiols, which causes the cancer cells to stop proliferating. In addition, the nitric oxide depletes the thiols, making the cancer cells more susceptible to the chemotherapy.

"The nitric oxide-releasing ability of the aspirin derivative NCX-4016 is enhanced by thiols, so I thought this type of treatment might work better in a tumor cancer cell that is rich in thiols, such as a resistant ovarian cancer," Kuppusamy said.

Kuppusamy plans to continue this research in animal models.

He collaborated with Dr. Louis Ignarro of the University of California School of Medicine in Los Angeles, who along with two colleagues won the 1998 Nobel Prize for Physiology or Medicine for their work in discovering the biologic role of nitric oxide.

Other Ohio State researchers involved in the study are Anna Bratasz, post-doctoral researcher and Nathan M. Weir, research assistant, both in the Davis Heart and Lung Research Institute; Narasimham L. Parinandi, assistant professor of pulmonary/critical care medicine and pharmacology; and Jay L. Zweier, director of the Davis Heart and Lung Research Institute
http://www.medilexicon.com/medicalnews.php?newsid=37870∞

Regular Paracetamol (acetaminophen) Reduces Ovarian Cancer Risk Significantly

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06 Jul 2006

The regular use of paracetamol (acetaminophen) can reduce a woman's risk of developing ovarian cancer by 30%, according to researchers from Athens University, Greece, who looked at eight studies covering more than three-quarters of a million women.

However, long-term use of paracetamol also raises the risk of kidney and liver failure. The researchers said more long term studies are needed to look into the effects. They also said that women should not start taking paracetamol because of the findings of this study.

About 1 in every 60 women develops ovarian cancer. For those that do develop it, survival rates are low. Under one third of ovarian cancer patients live longer than five years after diagnosis. The main reason for its high death rate is that diagnosis usually happens when the cancer is well advanced.

You can read about this study in the British Journal of Clinical Pharmacology.

The researchers looked at data from the UK, USA and Denmark, dating from 1996 to 2004. Of the 746,000 women, 4,405 had ovarian cancer. They found a significant link between ovarian cancer protection and ?regular' use of paracetamol. ?Regular', in this study, meant 30 tablets per month or more.

The researchers stressed that they do not know whether the cancer-protecting benefits outweigh the increased risk of liver and kidney failure. As a cancer-protective link has been identified, they said, further research should be carried out.
http://www.medilexicon.com/medicalnews.php?newsid=46669∞

Addition Of Topotecan To Standard Treatment Is Not Recommended For Ovarian Cancer Patients

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04 Aug 2006

The drug topotecan does not increase survival for ovarian cancer patients when used with standard chemotherapy in first-line treatment and is not recommended for future use, according to a phase III study in the August issue of the Journal of the National Cancer Institute.

Standard treatment for advanced ovarian cancer involves a combination of carboplatin and paclitaxel. Past studies have shown that this treatment is effective and has low toxicity. However, cancer recurrence and death rates remain high.

Jacobus Pfisterer, M.D., of the Universtitatsklinikum Schleswig-Holstein in Kiel, Germany, and colleagues randomly assigned 1,308 patients with untreated ovarian cancer to receive paclitaxel and carboplatin followed by either topotecan or surveillance. The researchers wanted to know how the drug regimen affected overall survival, progression-free survival, and quality of life.

Topotecan followed by treatment with carboplatin and paclitaxel did not improve patients' length of survival or survival without cancer recurrence. Topotecan treatment increased the frequency of blood-related toxicities and infections, which require extra medical care. The authors suggest that topotecan should not be used as part of first-line treatment in ovarian cancer patients.

The authors write, "Carboplatin-paclitaxel remains the standard of care for patients with advanced ovarian cancer."

In an accompanying editorial, William P. McGuire, M.D., of the Weinberg Cancer Institute in Baltimore, Md., discusses problems with chemotherapy trials for ovarian cancer, and suggests targeted therapies, such as angiogenesis inhibitors should be considered for future trials. He writes, "It seems that we are at a turning point in the design of clinical trials for ovarian cancer. We can continue to ask easier and, in my opinion, less important questions [...] Or we can 'bite the bullet' and use all of our valuable patient resources to evaluate whether ovarian cancer responds to the targeted therapies as other solid tumors have."
http://www.medilexicon.com/medicalnews.php?newsid=48589∞

Ovarian Cancer Tumors Shrink In Preclinical Trial By Fatty Spheres Loaded With SiRNA

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18 Aug 2006

A molecular "off" switch packaged in a tiny sphere penetrates deeply into ovarian cancer tumor cells, stifling a troublesome protein and drastically reducing the size of tumors, researchers at The University of Texas M. D. Anderson Cancer Center report in the Aug. 15 edition of Clinical Cancer Research.

The mouse model experiment, featured on the cover of the journal, demonstrates a potent delivery system for short interfering RNA (siRNA) to attack cancer, says senior author Anil Sood, M.D., associate professor in the Departments of Gynecologic Oncology and Cancer Biology at M. D. Anderson.

"Short interfering RNA is a great technology we can use to silence genes, shutting down production of harmful proteins," Sood says. "It works well in the lab, but the question has been how to get it into tumors." Short pieces of RNA don't make it to a tumor without being injected directly, and injection methods used in the lab are not practical for clinical use.

The research team took siRNA that targets a protein that helps ovarian cancer cells survive and spread and rolled it into a liposome -- a lipid ball so small that its dimensions are measured in nanometers (billionths of a meter).

Getting the siRNA inside tumor cells is important, Sood said, because the targeted protein, focal adhesion kinase (FAK), is inside the cell, rather than on the cell surface where most proteins targeted by cancer drugs are found. "Targets like FAK, which are difficult to target with a drug, can be attacked with this liposomal siRNA approach, which penetrates deeply into the tumor," Sood said.

Mice infected with three human ovarian cancer cell lines derived from women with advanced cancer were treated for 3-5 weeks. They received liposomes that contained either the FAK siRNA, a control siRNA, or were empty. Some mice received siRNA liposomes plus the chemotherapy docetaxel.

Mice receiving the FAK-silencing liposome had reductions in mean tumor weight ranging from 44 to 72 percent compared with mice in the control groups. Combining the FAK-silencing liposome with docetaxel boosted tumor weight reduction to the 94-98 percent range.

These results also held up in experiments with ovarian cancer cell lines resistant to docetaxel and to the chemotherapy drug cisplatin.

The FAK-silencing liposome and the liposome with chemotherapy also reduced the incidence of cancer by between 20 and 50 percent in all tested cancer lines.

In addition to its anti-tumor effect, the researchers found that the therapeutic liposome attacked the tumor's blood supply, especially when combined with chemotherapy. By inducing cell suicide (apoptosis) among blood vessel cells, the treatment steeply reduced the number of small blood vessels feeding the tumor, cut the percentage of proliferating tumor cells and increased cell suicide among cancer cells.

Sood and Professor of Molecular Therapeutics Gabriel Lopez-Berestein, M.D., an expert in liposomal therapeutics, cite at least two factors for the success of the anti-FAK liposome.

"This particle is so small, it has no problem getting through the tumor's vasculature and into the tumor," Lopez-Berestein says. The FAK-targeting liposome ranges between 65 and 125 nanometers in diameter. Blood vessels that serve tumors are more porous than normal blood vessels, with pores of 100 to 780 nanometers wide. Normal blood vessel pores are 2 nanometers or less in diameter.

Second, the liposome -- a commercially available version known as DOPC -- has no electrical charge. Its neutrality provides an advantage over positively or negatively charged liposomes when it comes to binding with and penetrating cells.

The next step for the FAK siRNA-DOPC liposome is toxicity testing. "So far it appears to be very well-tolerated," Sood says. "We hope to develop this approach for clinical use in the future."

In addition to ovarian cancer, FAK is overexpressed in colon, breast, thyroid, and head and neck cancers.
http://www.medilexicon.com/medicalnews.php?newsid=49781∞

New Approach To Early Detection Of Ovarian Cancer

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23 Aug 2006

Despite advances in surgery and chemotherapy, ovarian cancer is still the most lethal form of gynecologic cancer and the fourth leading cause of cancer death among women in the United States; claiming 16,210 lives in 2005.

Survival rates for ovarian cancer have remained stubbornly low because symptoms are often vague and mimic other conditions, and the lack of a cost-effective, reliable test to diagnose this ?silent killer? early, when it is most curable. A test is urgently needed that would rival the positive impact on survival that the Pap smear and mammography have had on cancers of the cervix and breast, respectively.

The statistics tell the story. Currently, three of every four women have advanced stage ovarian cancer when they are diagnosed, and only 25 percent of these women survive for five years. In contrast, the one woman in four diagnosed with early stage disease has a five-year survival rate exceeding 90 percent.

Now, innovative research at Roswell Park Cancer Institute and the University at Buffalo has produced compelling evidence that a simple blood test for early ovarian cancer screening might be developed sooner rather than later.

Scientists at these institutions have used sophisticated computer-modeling programs to interpret data from nuclear magnetic resonance (NMR) analyses of blood samples and produce cellular profiles that show the identities, structures and proportions of metabolites (metabonomics).

This NMR-based metabonomics approach has identified characteristics, known as biomarkers, in blood samples that can leave a ?biomolecular signature? that distinguishes women with early stage ovarian cancer from healthy women. Scientists believe that these biomarkers could be developed into a screening test for ovarian cancer.

However, before this simple blood test can be developed, researchers will use the same approach to hone in on the specific metabolite (or metabolites) responsible for differences between healthy women and cancer patients, and make early diagnosis of ovarian cancer possible. These metabolites also could be targets for therapy.

Scientists believe that this NMR-based metabonomics approach will not only benefit thousands of women each year, but have practical implications in other types of cancer as well.
http://www.medilexicon.com/medicalnews.php?newsid=50262∞

First Patient Treated In Phase III Ovarian Cancer Trial

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28 Nov 2006

Marshall Edwards, Inc. today announced that the first patient had commenced treatment in the Phase III "OVATURE" clinical trial at The Royal Women's Hospital in Melbourne, Australia.

Royal Women's is one of 60 hospitals that will be participating in this multi-center multi-national ovarian cancer study to confirm the effectiveness of phenoxodiol in resensitizing patients to chemotherapy.

Thirty of these hospitals will be in the U.S., 25 in Europe and 5 in Australia.

The total number of patients to be treated in this pivotal study is 470, with half to be on a treatment regime of phenoxodiol and the chemotherapeutic drug carboplatin, and half on a placebo and carboplatin.

The primary outcome of the trial is the assessment of the relative time it takes for the ovarian cancer to progress. An analysis of interim results will be possible after 95 patients have progressed with their disease.

The trial is being run under arrangements approved by the U.S. Food and Drug Administration (FDA) known as a Special Protocol Assessment (SPA). This provides for the interim analysis of the data, which if significant can be used to support a request for grant of marketing approval.

Professor Michael Quinn of Royal Women's Hospital in Melbourne said the Royal Women's Hospital along with the Yale University Medical School had already conducted a Phase II study, where phenoxodiol was shown to have a chemosensitizing effect on ovarian cancer when chemotherapy had previously failed.

"We are now hopeful that a positive outcome of this multi-center study will be a significant medical advance for thousands of women with late stage ovarian cancer whose tumors have become insensitive to the existing chemotherapeutic drugs," Professor Quinn said.

The Chief Executive Officer of Marshall Edwards, Inc., Mr. Christopher Naughton, said the Phase III Ovature study was a significant milestone for the Company.

"Over the next 12 to 18 months we expect the interim results from this multi-national clinical trial which may lead to the first approval for phenoxodiol," Mr. Naughton said.

Mr. Naughton said there are also other cancer types for which phenoxodiol has shown promise and the Company would be proceeding in the year ahead with a strategy to expand the drug's utility into those other cancers as both a chemosensitizer and as a monotherapy.

Ovarian cancer is the most lethal gynecological malignancy and the fifth leading cause of cancer-related death in women in the United States. The high mortality rate is due mainly to the inability to detect early disease with approximately 80 per cent of patients being diagnosed in advanced stage of disease.

About phenoxodiol:

Phenoxodiol is an investigational drug and, as such, is not commercially available. Phenoxodiol 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 restores the ability of chemoresistant tumor cells to undergo apoptosis in response to chemotherapy. The putative molecular target for phenoxodiol is a tumor-specific protein, accounting for the highly selective nature of the drug.
http://www.medilexicon.com/medicalnews.php?newsid=57557∞

New Kinds Of Cancer-Fighting Antibodies Analyzed By Researchers From The University Of Navarra

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11 Mar 2007

Two researchers from the University Hospital and the Center for Applied Medical Research (CIMA) from the University of Navarra have published an article in Nature Cancer Reviews, one of the leading scientific journals in the area of cancer studies. The article, written by Ignacio Melero and Sandra Hervas-Stubbs, together with other scientists from the United States and Great Britain, addresses the use of a new pharmaceutical family with practical applications in cancer and chronic viral illnesses.

Specifically, the article discusses using monoclonal antibodies in order to stimulate the immune system. In this therapy the antibodies are directed to the immune system cells in order to provoke a stronger reaction against cancer. This has the advantage of exploiting a mechanism with an action distinct from the other strategies currently being used to treat cancer, and is capable of interacting with the current treatments so as to make both forms of treatment more powerful.

Currently this treatment is being tested in patients with melanoma, kidney and ovarian cancer because there are more ways of measuring the response of the immune system, but he expects to be able to expand this to include other forms of cancer.

Five cancer-fighting agents being tested

The first cancer-fighting agent of this kind, anti-CTLA-4, began to be tested in patients in 1999. In melanoma treatment, between 15 and 20% of clinical objectives have been reached (reduction or disappearance of the tumor), which the researchers see as a positive sign to continue with the research.

Currently, the researchers study its benefits in cancer survivors through two clinical tests in the third phase. In two years we will test its use as the sole means of treatment, and we will need more time in order to know if its effects in treatment combinations are as positive as the results on test animals predict.

Aside from this, there are another four members of this monoclonal antibiotic family, which stimulate the immune system, currently being developed. Their use in patients began a year and a half ago, and to date no conclusions as to their effectiveness has been published.
http://www.medilexicon.com/medicalnews.php?newsid=64703∞

Potential For Diagnosis, Imaging, Treatment And Prognosis In Ovarian Cancer

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13 Mar 2007

Researchers have identified markers unique to the cells of blood vessels running through ovarian tumors. The finding, while preliminary, could one day improve screening, diagnosis and treatment for this disease.

The team of researchers from the University of Michigan, University of Pennsylvania, and universities in Greece and Italy, used a laser technique to isolate blood vessel cells from 21 ovarian tumors and four normal ovarian tissue samples. From there, they were able to determine which genes the vascular cells expressed.

The results identified more than 70 markers that were present in large amounts in the blood vessels of cancer tissue but not in the vessels of normal tissues. The researchers went on to study in detail 12 markers that had not previously been linked to tumor blood vessels. The study appears in the March 1 issue of the Journal of Clinical Oncology.

"Some of these genes, depending on how highly expressed they were in the tumor vasculature, were also prognostic of a patient's survival. We suspect when these genes are highly expressed it may be a sign of a tumor that's able to grow blood vessels more efficiently, and therefore is more aggressive. This may help us down the road in treatment decisions," says lead study author Ronald Buckanovich, M.D., Ph.D., assistant professor of internal medicine and obstetrics and gynecology at the University of Michigan Medical School. Buckanovich was at the University of Pennsylvania when he conducted this research.

The study analyzed the largest number of samples to date in tumor vasculature, or blood vessel, profiling. While many of the genes identified in this analysis have been shown previously to be involved in tumor vasculatures for other cancer types, several of the markers appear to be new.

In addition, the researchers were able to determine that some of the markers present in large amounts in ovarian tumors were not expressed by normal ovaries or other healthy organs. The researchers also found these markers were not present in normal reproductive tissues that experience blood vessel growth, such as the placenta or endometrium. This suggests that the markers are specific to tumors and would not be mistaken for normal blood vessel growth in women of reproductive age.

If the markers do prove to be specific to ovarian tumors, researchers believe that could be a new avenue to develop drugs that would target the blood vessels and strangle the tumor.

Biomarkers are also seen in other cancer types as a potential screening tool. A new way of detecting ovarian cancer could make a significant dent in this disease, where 70 percent of patients are diagnosed after the tumor has grown large or spread. There are few or no symptoms early in the disease and no effective screening tests. Early diagnosis is crucial, marking the difference between a 95 percent survival rate for cancers found at the earliest stage and 20 percent survival among patients diagnosed with advanced disease.

"All the things we could hope for are present with this approach: It has potential for diagnosis, imaging, treatment and prognosis. It needs more work and much more confirmation, but our early results are promising," Buckanovich says.

Continued research will look at developing antibodies and methods to detect these novel proteins. "In some cases, these are genes that many people have never worked on before," Buckanovich says.
http://www.medilexicon.com/medicalnews.php?newsid=64789∞

Potential 'Smart' Therapies For Breast, Ovarian Cancer from UBC Discovery

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21 Mar 2007

New non-toxic and targeted therapies for metastatic breast and ovarian cancers may now be possible, thanks to a discovery by a team of researchers at the University of British Columbia.

In a collaboration between UBC stem cell and cancer scientists, it was found that a protein called podocalyxin - which the researchers had previously shown to be a predictor of metastatic breast cancer - changes the shape and adhesive quality of tumour cells, affecting their ability to grow and metastasize. Metastatic cancer is invasive cancer that spreads from the original site to other sites in the body.

The discovery demonstrated that the protein not only predicted the spread of breast cancer cells, it likely helped to cause it. The findings were recently published online by the Public Library of Science.

"We believe we've found a new important culprit in metastatic breast cancer, which opens up an entirely new avenue of cancer research," says Calvin Roskelley, an associate professor of cellular and physiological science who specializes in breast cancer and is co-senior principal investigator. "The culprit is hiding in plain sight on the surface of tumour cells, so we are now developing "smart" molecules to block its function. The ultimate goal is to generate new targeted, non-toxic treatments - very different from the standard 'slash and burn' chemotherapy."

The researchers found that podocalyxin significantly expands the non-adhesive face of cells, allowing individual cells to brush aside adhesion molecules situated between tumour cells. The "freed" cells then move away from the original site to form new tumours at other sites. Also, the protein causes tumour cells to sprout microvilli, or hair-like projections, that may help propel cancer cells to other sites.

In addition, when the protein expands the non-adhesive face of cells it drags along with it a second protein called NHERF-1 - a protein shown by others to be implicated in cell growth and invasion. The researchers now believe the mechanism applies to difficult-to-treat invasive breast and ovarian cancers.

"We're now tapping into what causes the characteristic cell shape changes seen in cancerous tumours and possibly how these cells grow and metastasize. It gives us a whole new target for therapy," says Assoc. Prof. of Medical Genetics and stem cell expert Kelly McNagny, co-senior principal investigator. "If we can block the protein, we may be able to stop the spread of cells."

Post-doctoral Fellow Julie Nielsen, of UBC's Biomedical Research Centre, and PhD student Marcia Graves of the Dept. of Cellular and Physical Sciences, were instrumental in designing and executing the research experiments, he adds.

Next steps involve advancing the research in animal models, designing antibodies to block the function of the protein and working with the UBC-based Centre for Drug Research and Development to identify new therapies to combat metastasizing cancer.

The researchers say information from this discovery may speed development of new therapies to within 10 years.

In 2006, more than 22,000 women were diagnosed with breast cancer and 5,300 died of it, according to estimates from the Canadian Breast Cancer Foundation. The Canadian Cancer Society estimates that approximately 2,300 new cases of ovarian cancer were diagnosed and about 1,600 women died from the disease in 2006.
http://www.medilexicon.com/medicalnews.php?newsid=65519∞

Association of Estrogen and Progestin Potency of Oral Contraceptives With Ovarian Carcinoma Risk

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20 Mar 2007

Galina Lurie of the University of Hawaii and colleagues conducted a population-based study involving 745 women living in Hawaii and Los Angeles who had been diagnosed with ovarian cancer, Reuters Health reports. The researchers also studied a comparison group of 943 women without cancer who had been matched by age and ethnicity to the 745 women to determine how levels of estrogen and progestin in oral contraceptive pills affect ovarian cancer risk. The researchers collected health information about the participants using standard questionnaires and interviewed participants using photo albums to identify the specific oral contraceptive pills participants had used. The study found that ovarian cancer risk decreased by 81% for women who took pills with low levels of estrogen and progestin, compared with 38% for women who took pills with high levels of the hormones. In addition, the study found that ovarian cancer risk decreased by 50% for women who took any type of oral contraceptive pill. "Up to 42% of ovarian cancers might have been avoided if all women used some form of combined oral contraceptive pills," Lurie said, adding, "An estimated 73% of ovarian cancers might have been avoided if all women used oral contraceptive pill formulation of low estrogen and low progestin".
http://www.medilexicon.com/medicalnews.php?newsid=65486∞

Peregrine Pharmaceuticals Completes Patient Enrollment In Bavituximab Combination Therapy Trial In Advanced Cancer Patients

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23 Mar 2007

Peregrine Pharmaceuticals, Inc. (Nasdaq: PPHM), a clinical stage biopharmaceutical company developing targeted therapeutics for the treatment of cancer and hepatitis C virus (HCV) infection, today announced that enrollment of the planned 12 evaluable patients in its Phase lb cancer trial has been completed. This trial at clinical sites in India is designed to assess the safety of bavituximab in combination with common chemotherapy agents in advanced cancer patients with metastatic disease who had failed prior therapy. Data from this study are expected to support the initiation of Phase II cancer trials later this year.

To date, the safety profile of bavituximab in combination with chemotherapy appears similar to that seen in advanced cancer patients undergoing chemotherapy treatment alone. Nine patients have completed their course of therapy and have been assessed for tumor response at the eight week scheduled MRI or CT scan. Of these, more than half of the patients achieved either disease stabilization or an objective tumor response. "Disease stabilization" is defined as less than a 20% increase in the size of the tumor up to a 30% reduction in tumor size, while "objective response" is defined as greater than a 30% reduction in tumor size. Both stable disease and objective response are considered potential signs of anti-tumor activity. Patients demonstrating either an objective tumor response or stable disease have been offered continued treatment with the combination regimen on a compassionate use basis.

"We are encouraged by the results seen to date in this first test of bavituximab in combination with common chemotherapy regimens," said Steven W. King, president and CEO of Peregrine. "Achieving stable disease and objective responses in these very ill advanced cancer patients is a promising sign, and we look forward to reporting top-line results as soon as patient follow-up and data analysis are complete. We are optimistic that these results, in combination with data from our ongoing U.S. Phase l cancer trial, will support advancing bavituximab into more extensive combination therapy cancer trials later this year."

The Phase Ib open label trial is designed to characterize the safety, tolerability and pharmacokinetics of bavituximab given in combination with standard chemotherapy regimens including docetaxel, gemcitabine and carboplatin/paclitaxel. These regimens are commonly used for treating major solid cancers, and the enrolled patients include those with breast, ovarian and lung cancers. Study patients are considered enrolled and evaluable for safety analysis after completing four of the planned eight weekly doses of bavituximab in combination with chemotherapy. The chemotherapy agent was administered for up to eight weeks on its standard prescribed administration schedule. Patients are also being evaluated for tumor response according to Response Evaluation Criteria in Solid Tumors (RECIST) parameters, receiving CT or MRI scans prior to therapy and at week eight, although this assessment is not a formal endpoint of the study.

Study participants are being followed for an additional four weeks after their last dose of bavituximab. Patients with stable or improved disease may continue with chemotherapy and bavituximab on a compassionate use basis. The trial is being conducted according to International Conference on Harmonization (ICH) and Good Clinical Practices (GCP) guidelines.

Bavituximab is a monoclonal antibody that targets and binds to a phospholipid called phosphatidylserine, which is located on the inside of normal cells but which becomes exposed on the outside of the cells that line the blood vessels of tumors, creating a specific target for anti-cancer treatments. Bavituximab is currently in clinical trials in the U.S. and India for the treatment of solid tumors and in the U.S. as a treatment for chronic hepatitis C infection. Extensive preclinical data demonstrate good anti-tumor activity in a variety of tumor types, especially when bavituximab is administered in combination with chemotherapy or radiation.
http://www.medilexicon.com/medicalnews.php?newsid=65871∞

New Research Results Show That Investigational Drug Phenoxodiol Targets Cancer Protein, Causing Cancer Cell Death

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02 May 2007

A new study further supports the unique mechanism of action of phenoxodiol, an investigational drug being studied for the treatment of ovarian cancer. The drug appears to work by targeting a certain tumor-specific protein, which triggers a series of events that selectively induce cancer cell death. Phenoxodiol is currently being studied in patients with resistant ovarian cancer, a disease that is estimated to kill more than 15,000 women this year in the U.S. alone.

In studies conducted thus far, phenoxodiol has exhibited an excellent safety profile, with few patients experiencing side effects attributed to the drug.

The new research was conducted by a team headed by Research Professor Michael Berridge Ph.D., at the Malaghan Institute of Medical Research - New Zealand's leading medical research facility focused on finding cures for cancer and other diseases.

Findings from the study, to be presented at the New Zealand Society of Oncology meeting to be held May 9-11, help explain the mechanism by which phenoxodiol induces cancer cell death. This new research supports previous findings by Professor James Morre, Ph.D. at Purdue University, which showed that phenoxodiol interacts with the tumor-specific protein, tNOX, to selectively block cancerous cells from dividing by switching off a variety of pro-survival signaling mechanisms within the cancer cell, causing it to die.

In cases of late-stage ovarian cancer, standard chemotherapy drugs often have a limited duration of use. The cancer can progressively lose its sensitivity to chemotherapy until cancer cells become unresponsive causing resistance, a major barrier to successful cancer treatment. In laboratory studies and Phase II clinical trials, phenoxodiol showed promise in restoring drug sensitivity to resistant cancer cells.

"Phenoxodiol has a unique mechanism of action not exhibited by other anticancer drugs in current use.," said Dr. Berridge. "By inhibiting plasma membrane electron transport selectively in cancer cells, phenoxodiol subjects these cells to stress that leads to cell death. This novel drug and its related analogues have the potential to enhance anticancer efficacy by a different mechanism, promising a new approach to management of solid tumors in a range of clinical settings. As the first compound to operate via this pathway, confirmatory evidence to validate the mechanism of action is very desirable."

Specific Findings Identify Specific Proteins Associated with Unlocking the Mystery for Why Cancer Cells don't Die the Way Healthy Cells Do

Evidence from this new study indicates that phenoxodiol inhibits proliferation of many cancer cell lines and some primary immune cells. Phenoxodiol induces the destruction of cancer cells by disrupting a stress pathway in the outer cell membrane, causing down regulation of the FLICE-inhibitory protein, FLIP, and resulting in caspase-dependent and independent degradation of the X-linked inhibitor of cell death, XIAP.

Phenoxodiol selectively limits plasma membrane electron transport in cancer cells, by binding to a cancer specific surface plasma membrane electron transport element on cancer cells thereby inhibiting their proliferation, whereas the compound has no such effect on normal healthy cells.

Multinational trial underway

Phenoxodiol in combination with carboplatin is currently being studied in a multi-national Phase III clinical trial called OVATURE, following positive findings of previous trials conducted at Yale-New Haven Hospital. The OVATURE trial will take place in 60 sites in the United States, Europe, and Australia. Preliminary results from the trial are expected within 18 months.

About phenoxodiol:

Phenoxodiol is being developed as a therapy for late-stage, chemo-resistant prostate, ovarian and cervical cancers. Phenoxodiol is an investigational drug and, as such, is not commercially available. 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 restores the ability of chemoresistant tumor cells to undergo apoptosis in response to chemotherapy. The putative molecular target for phenoxodiol is a tumor-specific protein, accounting for the highly selective nature of the drug.
http://www.medilexicon.com/medicalnews.php?newsid=69537∞

Combined Molecular-targeted And Hormonal Therapies Offer Promise In Treating Ovarian Cancer

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08 May 2007

A combination of molecular-targeted therapy and hormonal therapy may be the most promising area of research for those seeking an effective treatment for ovarian cancer, according to a new review in the International Journal of Gynecological Cancer.

"Several clinical trials have confirmed the role of hormone therapy in recurrent ovarian cancer treatment, especially in patients with low-grade tumors," says review author Dr. Siqing Fu, an assistant professor of oncology at the University of Texas at Houston. "However, more research is needed to determine whether combining molecular-targeted therapy with hormonal therapy would be a more effective option."

Ovarian cancer is the deadliest of gynecological cancers; approximately 70 percent of patients are diagnosed in the later stages, when the 5-year survival rate drops below 25 percent. Traditional chemotherapy has proven to be generally ineffective against recurrent ovarian cancer, which has led researchers to investigate novel treatments.

"While a cure is unlikely, the goals of treatment are to control tumor-related symptoms and to improve or maintain quality of life," says Dr. Fu. "After surveying the latest research, combined molecular-targeted and hormonal therapy offers the greatest promise in achieving these goals and therefore deserves further investigation."
http://www.medilexicon.com/medicalnews.php?newsid=70336∞

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