Yale Researchers Indicate That Novogen Compound NV-128 Induces Cell Death in Chemo-Resistant Ovarian Cancer Cells

“An abstract for an oral presentation to be given at the Annual Meeting of the American Association for Cancer Research, April 12 – 16, in San Diego, Calif., is now available (abstract number 4926) at http://www.aacr.org. The abstract, describing work undertaken by Professor Gil Mor and colleagues at the Yale University School of Medicine, indicates that the compound NV-128, developed by Novogen Limited (ASX: NRT) (NASDAQ: NVGN), may be useful for the maintenance of remission in chemo-resistant ovarian cancer.NV-128 is able to induce cell death through the inhibition of the mTOR pathway [mTOR pathway diagram] in cancer cells. NV-128 inhibition of the mTOR pathway results in caspase-independent apoptosis and autophagy. Only a few other compounds are in the mTOR antagonist class, providing an alternative to drug candidates reliant on caspase dependent cell death as their mechanism of action.

At the annual meeting of the Society for Gynecological Oncology in Tampa, earlier this month, several key speakers addressed the significance of mTOR antagonists in cancer therapeutics.

mTOR is a key intracellular kinase, integrating proliferation and survival pathways. In cancer cells, mTOR signals enhance tumour growth and may be associated with resistance to conventional therapy. Inhibition of mTOR may shut down many of these survival pathways, including the proteins protecting the mitochondria. It is believed that NV-128 affects the catalytic dynamics of mTOR in order to achieve apoptosis.

NV-128 works differently from therapies that are dependent on caspases to trigger apoptosis. Through the inhibition of mTOR, NV-128 is capable of triggering a cascade of events that leads to mitochondrial damage and cell death. Interestingly, since NV-128-induced cell death is completely caspase-independent, it could be effective on cancer cells characterised by high resistance to cell death and representative of late stage chemorefractory disease.”

Quoted Source: [ “Yale researchers to present data indicating that NV-128 uses mTOR pathway to induce cell death,” Novogen Limited News Release dated March 25, 2008.]

Comment: NV-128 represents a novel intracellular kinese inhibitor that disrupts chemo-resistant ovarian cancer cells. V-128 is an analogue of Novogen’s lead anti-cancer agents triphendiol (triphendiol), and phenoxodiol (NV-06). Phenoxodiol has demonstrated efficacy as a monotherapy and as a chemosensitizer against cancer cell lines representative of non-small cell lung carcinoma (NSCLC). Phenoxodiol is also currently being used in the OVArian TUmor REsponse (OVATURE) clinical trials for recurrent ovarian cancer being conducted in the U.S., Europe and Australia. Proof of concept xenograft studies have confirmed that orally delivered NV-128 retards NSCLC tumor proliferation. Efficacy studies are in progress in pre-clinical in vitro studies against late stage colorectal, breast, and gastric cancers and hepatocellular carcinoma, both as a monotherapy and in combination with current standard of care drugs.

The Life Saving Effect of Johanna’s Law

Johanna’s Law is named after Johanna Silver Gordon, a dynamic woman and former schoolteacher, who lost her life to ovarian cancer despite being a health conscious woman who visited the gynecologist regularly. Sadly, Johanna did not recognize the early symptoms and warning signs of ovarian cancer until AFTER being diagnosed with an advanced stage of the disease. Lack of symptom recognition contributed to a lengthy —and ultimately lethal — delay in Johanna’s diagnosis. Tragically, Johanna’s story of delayed diagnosis is all too common. Thousands of U.S. women annually are stunned not only by diagnoses of gynecologic cancer, but also learn after the fact that the symptoms experienced in the months prior to their diagnoses were common symptoms of these cancers. The problem is particularly common with respect to ovarian cancer, where a pervasive lack of knowledge regarding symptoms commonly leads to lengthy delays in disease diagnosis. Additionally, women are frequently misdiagnosed with benign conditions before the correct diagnosis is made by a health care professional.

Source: [ Johanna’s Law Alliance for Women’s Cancer Awareness, Sheryl Silver (Johanna’s sister), Founder/President].

Johanna’s Law

The Gynecologic Cancer Education and Awareness Act (P.L. 109-475) was passed by the 109th Congress and signed into law in early 2007. This law provides up to $16.5 million for awareness and education through a national public service campaign that will include written materials and public service announcements.

The passage of Johanna’s Law was required because too many women are diagnosed in later stages of gynecologic cancers; if these women were diagnosed earlier, their chances of survival would be greater. Women with ovarian cancer have a five-year relative survival rate of more than 90 percent if diagnosed in Stage I. Unfortunately, less than 20 percent of ovarian cancer cases are diagnosed in Stage I. The overall five-year relative survival rate for ovarian cancer is 45 percent. Due to the lack of an early screening test for ovarian cancer (however, see Yale Blood Test Detects Early Stage Ovarian Cancer with 99% Accuracy), women and health care providers must be aware of the signs and symptoms of gynecologic cancers to act in the best interests of women.

Legislative History

In 2004, the bill was introduced in the U.S. House of Representativies (House). In 2005, the bill was introduced in the U.S. Senate (Senate). The House held a hearing on the bill in 2006. It was passed by unanimous consent of the Senate in 2006 and signed into law by President George W. Bush in early 2007. The Ovarian Cancer National Alliance (the Alliance) worked to secure the implementation funding of Johanna’s Law through the U.S. Congressional appropriations process. The Alliance requested $9 million to implement Johanna’s Law. In the 2008 fiscal year, this program was appropriated $6.5 million by the U.S. Congress. The Alliance will request the U.S. Congress to fully fund Johanna’s Law program for $10 million in the 2009 fiscal year.

Adoption of the Ovarian Cancer Symptoms Consensus Statement

In mid-2007, a number of medical organizations and related groups agreed upon and released a Consensus Statement listing the primary symptoms of ovarian cancer. These symptoms, long recognized by patients, and scientifically documented in the medical literature, are:

* Bloating
* Pelvic or abdominal pain
* Difficulty eating or feeling full quickly
* Urinary symptoms (urgency or frequency)

A woman who experiences these symptoms persistently for several weeks should consult with her doctor, preferably a gynecologist. Prompt medical evaluation may lead to detection at the earliest possible stage of the disease. Early stage diagnosis is associated with an improved prognosis.

Often, women and health care providers mistake ovarian cancer for gastrointestinal disorders or early menopause. While symptoms may seem vague, they can be lethal without proper medical intervention. Johanna’s Law provides for an education and awareness campaign that will educate health care providers with respect to, and increase women’s awareness of, this disease.

Source: [Johanna’s Law: The Gynecologic Cancer Education and Awareness Act of 2007, Ovarian Cancer National Alliance website]

Comment: The impetus for adoption of Johanna’s Law can be traced to Sheryl Silver, Johanna’s sister. Sheryl is the founder and president of the Johanna’s Law Alliance for Women’s Cancer Awareness. The adoption of Johanna’s Law should heighten the awareness of women in the U.S. regarding the primary symptoms and warning signs associated with ovarian cancer in the earliest stages of the disease. Sheryl Silver’s perseverance on behalf of the memory of her sister led to the adoption of a law that will undoubtedly save thousands of lives in the future.

Liposomal siRNA — Genetic On/Off Switches That Target Ovarian Cancer Through the Trojan Horse Effect

Use of Liposomal siRNA to Target Ovarian Cancer Protein Known as “Interleukin-8 (IL-8)”

“A protein that stimulates blood vessel growth worsens ovarian cancer, but its production can be stifled by a tiny bit of RNA wrapped in a fatty nanoparticle, a research team led by scientists at The University of Texas M. D. Anderson Cancer Center reports in the Journal of the National Cancer Institute.

The protein IL-8 is a potential therapeutic target in ovarian cancer,’ said senior author Anil Sood, M.D., professor in the M. D. Anderson Departments of Gynecologic Oncology and Cancer Biology.

The paper demonstrates that high IL-8 expression in tumors is associated with advanced tumor stage and earlier death for ovarian cancer patients. Lab experiments and research in a mouse model show that short interfering RNA (siRNA) can cut IL-8 expression, reducing tumor size by attacking its blood supply.

‘This comprehensive analysis – with human data, animal data and lab experiments to highlight the molecular mechanisms involved – helps us develop the new targets needed for a more effective approach against ovarian cancer,’ Sood said.

Interleukin-8 is overexpressed in many types of cancer and has previously been shown to promote tumor growth, new blood vessel growth known as angiogenesis, and metastasis, the spread of cancer to other organs. ‘In the long run, this research will have applications in other cancers as well,’ Sood said.

His research focuses on ovarian cancer, for example, while senior co-author Menashe Bar-Eli, Ph.D., professor in M. D. Anderson’s Department of Cancer Biology, examines IL-8’s role in melanoma.

Impact on survival

Ovarian cancer is often detected in late stages. Initial treatment includes surgery and taxane- or platinum-based chemotherapy regimens that keep the cancer at bay for a time in most patients. Recurrence is common and often lethal.

To examine IL-8’s role in ovarian cancer, the researchers analyzed tumors from 102 patients diagnosed and treated between 1988 and 2006 at M. D. Anderson and the University of Iowa. Of those, 43 had tumors with high levels of IL-8 and 59 had low levels. The median survival of those with high IL-8 tumors was 1.62 years, compared with 3.79 years for those with low expression of the protein.

All 43 tumors with high expression of IL-8 were of high grade and 42 of 43 were advanced, either stage III or IV tumors. By comparison, 10 of 59 tumors with low IL-8 expression were early stage tumors and six were of low grade.

Shrinking tumors

Genes transcribe single strands of RNA that in turn are ‘read’ by ribosomes to produce proteins. siRNAs are short, double-stranded bits of RNA capable of halting that process. The team confirmed in a lab experiment that a specific siRNA silences IL-8 and then tested it against two lines of ovarian cancer in a mouse model.

Sood, Gabriel Lopez-Berestein, M.D., professor in M. D. Anderson’s Department of Experimental Therapeutics, and colleagues are building an arsenal of siRNAs capable of silencing genes that produce cancer-promoting proteins. They packaged siRNA that stymies IL-8 into a small ball of fat known as a liposome, a combination they developed to overcome a problem – siRNA is hard to deliver to tumors.

Tumors shrank by a median of 32 percent and 52 percent in the two cancer lines among mice that received injections of the IL-8 siRNA liposome compared to those receiving control siRNA or empty liposomes.

Mice that got both the IL-8 siRNA plus the taxane-based chemotherapy drug docetaxel [Taxotere®] had median tumor weight reduction of 90 percent and 98 percent in the two cell lines. Mice with control siRNA plus docetaxel saw reductions of 67 and 84 percent.

Finally, they tested the approach in mice with an ovarian cancer cell line known to be resistant to taxane-based drugs such as docetaxel. IL-8 siRNA alone reduced the size of these tumors by 47 percent, and when combined with docetaxel reduced tumor size by 77 percent, suggesting that the combination re-sensitizes a resistant tumor to taxanes.

The team gauged the impact of IL-8 siRNA on tumor blood supply by measuring the density of blood vessels in the tumor. The IL-8 siRNA alone reduced blood vessel density by 34 percent and 39 percent in two cancer lines.

Clinical Prospects

‘These are encouraging results. We want to move one of our siRNA agents into the clinic to test its potential for therapy,’ Sood said, ‘and then in the longer term, we’ll consider moving additional siRNA agents into the clinical arena.’

The IL-8 siRNA liposome is the third developed by Sood’s and Lopez-Berestein’s team. Two others target the oncoproteins FAK and EphA2. The EphA2 siRNA liposome is closest to Phase I clinical trial, with required toxicology studies nearly complete. A clinical trial could begin within a year.

Methods used to inject siRNA in high volumes for research purposes are impractical for human therapy. Sood and Lopez-Berestein developed the liposomal approach to ensure that the siRNA reaches the cell intact so it can silence the targeted gene. Their research has shown that the liposome penetrates deeply into cells to deliver its siRNA.

Research reported in JNCI was funded by grants from the National Cancer Institute of the National Institutes of Health, including M. D. Anderson’s Specialized Program of Research Excellence in Ovarian Cancer; the Ovarian Cancer Research Fund, Inc.; and the Zarrow Foundation.”

Quoted Source: [“Researchers Identify and Shut Down Protein that Fuels Ovarian Cancer, M. D. Anderson-led team pinpoints blood vessel promoter’s role and targets it with siRNA,” M.D Anderson News Release, dated February 26, 2008]. See also “Effect of Interleukin-8 Gene Silencing With Liposome-Encapsulated Small Interfering RNA on Ovarian Cancer Cell Growth;” Merritt,W.M., Lin,Y.G., Spannuth,W.A., Fletcher,M.S., Kamat,A.A., Han,L.Y., Landen,C.N., Jennings,M., Geest,K., Langley,R.R., Villares,G., Sanguino,A., Lutgendorf,S.K., Lopez-Berestein,G., Bar-Eli,M.M., Sood, A.K.; Journal of the National Cancer Institute 2008 100(5):359-372.

Use of Liposomal siRNA to Target Ovarian Cancer Protein Known as “Focal-Adhesion Kinase (FAK)”

Recent work reported in October 2006 by Dr. Anil Sood at M.D. Anderson involved the use of a targeted “siRNA” liposome in mice to identify and correct defective ovarian cancer cells. M. D. Anderson researchers used siRNA (which acts as a genetic “on/off” switch) to target an ovarian cancer protein known as focal-adhesion kinase (FAK), which is present in all ovarian cancer cells. FAK helps ovarian cancer cells survive and spread. The siRNA was rolled into a liposome – a ball of fat so small that its dimensions are measured in nanometers (billionths of a meter). Because of their tiny size, these liposomes have no problem traveling through the blood supply into cells that make up tumors through the so-called “Trojan Horse” effect. To test how well it worked, mice that were implanted with human ovarian tumors were given injections of the therapy for three to five weeks. The mice ovarian tumors experienced a 44% to 72% reduction in weight. Adding chemotherapy to the treatment boosted tumor weight reduction to the 94% to 98% range. The next step for the FAK siRNA liposome is testing for toxicity prior to studies in human patients.

Source: [ “Novel Therapy Shrinks Ovarian Tumors in Mice, Genetic Fragments Turn Off Cancer Growth Switch,” Cancer Newsline, October 2006, M.D. Anderson Cancer Center, University of Texas.]

Use of Liposomal siRNA to Target the Ovarian Cancer Kinase Known as “EphA2”

In an earlier in vitro studies, Anil Sood, M.D. et. al. demonstrated that when EphA2-targeting siRNA was combined with paclitaxel [Taxol®], tumor growth was dramatically reduced compared with treatment with paclitaxel and a nonsilencing siRNA. These studies show the feasibility of siRNA as a clinically applicable therapeutic modality.

Source: [“Therapeutic EphA2 Gene Targeting In vivo Using Neutral Liposomal Small Interfering RNA Delivery;” Landen,C.N., Chavez-Reyes, A., Bucana, C., Schmandt, R., T. Deavers, M., Lopez-Berestein, G. and Sood, A.K., The University of Texas M.D. Anderson Cancer Center, Houston, Texas; Cancer Research 65, 6910-6918, August 1, 2005.

Comment: The ultimate use of siRNA to treat ovarian cancer in humans holds future promise. Ovarian cancer survivors should monitor the development of this liposomal siRNA form of treatment because its use in human clinical trials could occur in the near future, assuming that pre-clinical trial toxicity tests demonstrate safety. Anil Sood, M.D. has developed the liposomal siRNA for IL-8, FAK, and EphA2. It is reported that human clinical trials with respect to the EphA2 siRNA treatment will begin within 12 months.

Bald Is Beautiful!

Periodically, the H*O*P*E* Blog will highlight a cancer survivor that makes a difference. Sharon Blynn is a prime example. In October 2000, Sharon Blynn was visiting her family in Miami when she discovered that her stomach pains were not caused by irritable bowel syndrome. Rather, the pain was caused by a rare, non-invasive form of ovarian cancer. Local doctors informed her that she would need surgery and chemotherapy.Rather than return to her home in New York, Sharon decided to seek treatment in Miami with the support of her family — the anticipated short family visit turned into a three year journey.

During her chemotherapy treatments, Sharon, who was in her 20s, recalls being the youngest ovarian cancer patient in the room. She also remembers her twin sister sleeping in the chair beside her bed and the women with cancer who would not look at themselves in the mirror because of surgery or hair loss.

Sharon was inspired by her experience and the people she met throughout her journey to start a website, baldisbeautiful.org, which is all about helping women living with cancer feel beautiful — she’s been shaving her head ever since. “Through my Bald Is Beautiful work,” she says, “I have found a new focus and purpose – a new level of joy.”

Sharon credits cancer with giving her a deeper sense of who she is and the importance of a healthy mind-body-spirit lifestyle. The disease also intensified her desire to share that message with people. “Cancer brought me closer to feeling alive in every part of my life, from how I feel about myself, to how I feel about my relationships with my family and friends, and my relationship with the whole world around me.” Source: [Bristol-Myers Squib website].

I encourage you to visit Sharon’s website and view her YouTube video — by doing so, you will truly discover her honesty, talent, and resilient human spirit.

“Courage doesn’t always roar. Sometimes courage is the quiet voice at the end of the day saying, ‘I will try again tomorrow.’”
–Mary Anne Radmacher

Who? Where? Two of the Most Important Choices When Facing An Ovarian Cancer Diagnosis.

Robert Bristow, M.D., Director of the Kelly Gynecologic Oncology Service and the Johns Hopkins Ovarian Cancer Center of Excellence, and colleagues highlight the importance of referring patients with suspected ovarian cancer to expert centers for their first surgery. By combining multiple studies of patients with stage III or IV ovarian carcinoma (6,885 patients) Bristow et al showed that consistent referral of patients with apparent advanced ovarian cancer to expert centers for primary surgery may be the best means currently available for improving overall survival. Even with the use of platinum based chemotherapy, maximal (or optimal or complete) cytoreduction was one of the most powerful determinants of cohort survival among patients with stage III or IV ovarian carcinoma. While the influence of platinum dose-intensity upon survival was not statistically significant, maximal cytoreduction was associated with a 50% increase of actuarial survival.

PubMed medical study abstract: “Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis,”Bristow, R.E., Tomacruz, R.S., Armstrong, D.K., Trimble, E.L., Montz, F.J., Kelly Gynecologic Oncology Service, Department of Gynecology and Obstetrics, Johns Hopkins Medical Institutions, Baltimore, MD 21287-1248, USA. rbristo@jhmi.edu, J. Clin. Oncol. 2002 Mar 1;20(5):1248-59.

Full Text of medical study: Journal of Clinical Oncology, Vol. 20, Issue 5 (March), 2002: pp.1248-1259.

Additional medical studies:

• “Specialized Hospital Care Associated With Better Survival in Dutch Ovarian Cancer Patients.” Liz Savage, J Natl Cancer Inst 2008 100: 375

• “Factors associated with the suboptimal treatment of women less than 55 years of age with early-stage ovarian cancer;” Chan J, Kapp D, Shin J, et al.; Gynecologic Oncology. 2008;108: 95-99.

• “In treating ovarian cancer, a little-known specialist can make a big difference” by Laurie McGinley, Health Matters, Wall Street Journal, November 17, 2007. (.PDF download)

• “Predictors of comprehensive surgical treatment in patients with ovarian cancer;” Goff B, Matthews B, Larson E, et al.; CANCER May 15, 2007 , Vol. 109, No. 10, pp. 2031=2042.

• “Access to gynecologic oncologists and its impact on survival of women with epithelial ovarian cancer;” Chan JK et al.; Gynecol Oncol. 2007;104(3): Abstract 17.

COMMENT: If you were recently diagnosed with ovarian cancer, these studies suggest that you should seek treatment from a medical institution(s) that (i) utilizes Gynecologic Oncologists as an essential part of the cancer diagnosis and treatment process, (ii) utilizes surgeons that possess high-end expertise with respect to gynecologic oncology surgical procedures such as maximum cytoreduction (e.g., gynecologic oncology surgeons), and (iii) conducts a high volume of gynecologic oncology surgeries and procedures resulting in best outcome. Refer to the resources below.

• List of NCI-designated Cancer Centers.

• List of National Comprehensive Cancer Network Members.

• 2007 U.S. News & World List of Best U.S. Hospitals (click on each hospital to determine its gynecological sub-specialty rating).

Advanced-stage Ovarian Cancer Patients With BRCA Live Longer, May Respond Better To Standard Treatment

“Two abstracts underscoring the importance of testing for BRCA1/2 mutations in women with ovarian cancer were presented at this week’s Society of Gynecologic Oncologists 39th Annual Meeting on Women’s Cancers, by researchers from The University of Texas M. D. Anderson Cancer Center.

In the first study, a multicenter research team led by M. D. Anderson found advanced- stage ovarian cancer patients with non-Ashkenazi Jewish BRCA (non-AJ BRCA) mutations experience longer progression-free and overall survival rates compared to those with sporadic ovarian cancer. The data confirms previous research which reported that among ovarian cancer patients of Ashkenazi-Jewish heritage, BRCA1/2 mutations (AJ BRCA) are associated improved long-term survival.

For this study, researchers examined 85 advanced-stage ovarian cancer patients with non-AJ BRCA mutations and 116 patients who did not express any type of BRCA mutation. Compared to patients without BRCA mutations, non-AJ BRCA carriers had longer progression-free survival of 19.0 vs. 27.8 months and improved overall survival of 65.6 vs. 101.4 months. Non-AJ BRCA patients had a 2.15 times greater odds of complete response to initial chemotherapy response over sporadic, non-carrier patients.

Karen Lu, M.D., associate professor in the Department of Gynecologic Oncology at M. D. Anderson and senior author on the study said the difference in survival rates indicate that individuals with BRCA mutations might respond better to standard chemotherapy for ovarian cancer. ‘Thus, it becomes increasingly valuable to know a patient’s BRCA status to guide and personalize treatment decisions,’ Lu said.

Majority of Patients Unaware BRCA Testing Available
A second study conducted at M. D. Anderson concluded that, despite being available for more than 10 years, a majority of women with ovarian cancer were unaware genetic counseling and testing for BRCA1/2 mutations was an option. Of the 225 ovarian cancer patients surveyed, 56 percent had not heard of BRCA testing. This lack of awareness was more profound in minorities – 69 percent of Hispanic and 88 percent of African American respondents were unaware of BRCA testing compared to 52 percent of white women.

Patients typically associate genetic testing with benefiting family members and offspring,’ Lu said. ‘Both of these studies illustrate that it is equally important for the cancer patient to get information from their doctors about genetic testing because it not only has implications for their family, but their own treatment and prognosis.’

She said that more than 85 percent of ovarian cancer patients surveyed would be willing to undergo BRCA testing if it would affect their care, but the cost of testing may be a barrier. ‘Currently, oncologists are inconsistent in their testing for BRCA mutations. Based on the treatment implications of our findings and the surprisingly low knowledge that such testing is available, we recommend developing ways to systematically evaluate every ovarian cancer patient for BRCA,’ Lu said.

A family history of breast and/or ovarian cancer is reported in approximately five percent to 15 percent of ovarian cancer cases, with BRCA1/2 mutations expressed in a significant proportion of these cases. …”

Quoted Source: [“Advanced-stage Ovarian Cancer Patients With BRCA Live Longer, May Respond Better To Standard Treatment,” M.D. Anderson News Release, dated March 10, 2008.] See also Survival in advanced-stage ovarian cancer patients with non-Ashkenazi Jewish BRCA mutations, Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: Abstract #5514.

Comment: Both studies illustrate the importance of obtaining genetic testing information from your doctor. This information is important for your family and relatives and your own treatment and prognosis.

SNS-595 Shows Promise For Platinum-Resistant Ovarian Cancer Patients

“Sunesis Pharmaceuticals, Inc. (Nasdaq: SNSS), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of novel small-molecule therapeutics, announced positive interim data from the company’s ongoing Phase 2 clinical trial of its lead product candidate, SNS-595, in platinum-resistant ovarian cancer patients.

In this Phase 2 clinical trial, single agent SNS-595 has demonstrated disease control (defined as stable disease, partial response or complete response) in 31 of 35 patients evaluable for best response using GOG-RECIST criteria. Of these 31 patients, one patient had a complete response, four patients had partial responses (two unconfirmed) and 26 patients had a best response of stable disease. All patients enrolled in the trial have previously failed treatment with platinum-containing regimens, and fourteen of the 35 patients have also failed prior treatment with doxorubicin HCl liposome injection (Doxil(R)). Both platinum-resistant and Doxil-resistant patients in the Phase 2 clinical trial have responded to SNS-595 therapy.

‘Recurrence rates among ovarian cancer patients remain high, and the majority of refractory patients are resistant to platinum-based therapies. Based on these interim data, SNS-595 appears to be a promising, active agent in a difficult-to-treat ovarian cancer patient population,’ said William P. McGuire, M.D., Medical Director of the Harry and Jeanette Weinberg Cancer Institute at Franklin, and a lead investigator for the Phase 2 trial.

Among forty-five patients with sufficient follow-up to yield safety data, SNS-595 was generally well tolerated at a dose level of 48mg/m2 administered once every three weeks. The most common adverse events reported thus far include nausea, fatigue, vomiting and alopecia. There was a low rate of febrile neutropenia or other Grade 3/4 adverse events, and manageable Grade 1/2 nausea or vomiting.

Based on the indications of clinical activity and the acceptable tolerability profile demonstrated to date among this patient population, the dose of SNS-595 in this trial has been increased to 60 mg/m2 over twenty-eight days. Patient accrual at this dose level is ongoing.

‘We are pleased by the strong signal of activity emerging from our Phase 2 clinical trial of SNS-595 at the 48mg/m2 dose level. Based on the drug’s observed safety profile and recommendations from advisors, we are exploring a higher dose of SNS-595 in this trial. Enrollment has begun at 60 mg/m2 and we expect to enroll approximately 30 patients at this dose by the third quarter of this year,’ said Daniel C. Adelman, M.D., Senior Vice President, Development and Chief Medical Officer of Sunesis. ‘Enthusiasm for SNS-595 among our clinical investigators is growing and enrollment in this trial has been accelerating. We expect to present further data from this Phase 2 clinical trial this year.’

The interim clinical results are being presented in a poster, “A Phase 2 Trial of SNS-595 in Women with Platinum-Refractory Epithelial Ovarian Cancer” (Abstract # 290), at the 39th Annual Meeting on Women’s Cancer hosted by the Society of Gynecologic Oncologists (SGO) in Tampa, Fla. through March 12, 2008.”

About SNS-595

SNS-595 is a novel naphthyridine analog, structurally related to quinolones, a class of compounds which has not been used previously for the treatment of cancer. SNS-595 is a specific DNA intercalator and topoisomerase II poison, causing replication-dependent site-selective double strand DNA damage, irreversible G2 arrest and rapid apoptosis. In non-clinical evaluations, SNS-595 demonstrates broad and potent activity in xenograft, syngeneic and drug-resistant models. In addition to the Phase 2 clinical trial in ovarian cancer patients, SNS-595 is currently being evaluated in combination with cytarabine in a Phase 1b acute leukemia clinical trial. In clinical trials conducted to date, SNS-595 has been generally well tolerated and has shown objective responses in both solid and hematologic tumor types.”

Quoted Source: [“Sunesis Pharmaceuticals Reports Positive Interim Data for SNS-595 Single-Agent Activity in Platinum-Resistant Ovarian Cancer”, MedicalNewsToday.com, March 11, 2008. (Emphasis added by posting author)].

Updates:

• SNS-595 Phase II Clinical Trial Preliminary Efficacy Results. PDF Document Download

• Open Recruiting for SNS-595 Phase II Clincial Trial entitled, “A Phase 2 Open-Label, Multicenter Study of SNS-595 Injection in Patients With Platinum-Resistant Ovarian Cancer.”

• “Sunesis Pharmaceuticals Presents Nonclinical Data on SNS-595 at the Annual Meeting of the American Association for Cancer Research — Nonclinical Studies Demonstrate that SNS-595 Acts through a Dual Mechanism and May Evade Common Drug Resistance Mechanisms Research Supports Current Clinical Development of SNS-595 in AML and Ovarian Cancer and Potential in Additional Indications,” Sunesis Pharmaceuticals Press Release dated April 14, 2008. PDF document download of 2008 AACR Annual Meeting Presentation Re SNS-595 (Poster 2830).
• “A Phase 2 Trial of Voreloxin (Formerly SNS-595) in Women with Platinum-Resistant Epithelial Ovarian Cancer,” 2008 American Society of Clinical Oncology Annual Meeting Presentation, May 31, 2008 (Adobe Reader PDF Document). See also, “A phase II trial of SNS-595 in women with platinum resistant epithelial ovarian cancer,” W. P. McGuire et. al., J Clin Oncol 26: 2008 (May 20 suppl; abstr 5582).

Yale Blood Test Detects Early Stage Ovarian Cancer With 99% Accuracy

“Researchers at Yale School of Medicine have developed a blood test with enough sensitivity and specificity to detect early stage ovarian cancer with 99 percent accuracy.Results of this new study are published in the February 15 issue of the journal Clinical Cancer Research. The results build on work done by the same Yale group in 2005 showing 95 percent effectiveness of a blood test using four proteins.

‘The ability to recognize almost 100 percent of new tumors will have a major impact on the high death rates of this cancer,’ said lead author Gil Mor, M.D., associate professor in the Department of Obstetrics, Gynecology & Reproductive Sciences at Yale. ‘We hope this test will become the standard of care for women having routine examinations.’

Epithelial ovarian cancer is the leading cause of gynecologic cancer deaths in the United States and three times more lethal than breast cancer. It is usually not diagnosed until its advanced stages and has come to be known as the “silent killer.”

This new phase II clinical trial included 500 patients; 350 healthy controls and 150 ovarian cancer patients. Mor and colleagues validated the previous research and used a new platform called multiplex technology to simplify the test into one single reaction using very small amounts of serum from the blood. The new platform uses six protein biomarkers instead of four, increasing the specificity of the test from 95 to 99.4 percent. The team looked for the presence of specific proteins and quantified the concentration of those proteins in the blood.

The Early Detection Research Network (EDRN) of the National Cancer Institute (NCI) independently evaluated the results of the test.

‘This is the most sensitive and specific test currently available,’ said Mor. ‘Previous tests recognized 15 to 20 percent of new tumors. Proteins from the tumors were the only biomarkers used to test for ovarian cancer. That is okay when you have big masses of tumors, but it is not applicable in very early phases of the tumor. Testing the proteins produced by the body in response to the presence of the tumor as well as the proteins the tumors produce, helped us to create a unique picture that can detect early ovarian cancer.’

Mor and colleagues have begun a phase III evaluation in a multi-center clinical trial. In collaboration with EDRN/NCI and Laboratories Corporation of America (LabCorp), they are testing close to 2,000 patients.

The test is available at Yale through the Discovery to Cure program. Yale has licensed the test to three companies: Lab Corp in the United States, Teva in Israel and SurExam in China.”

Quoted Source: [Yale University Press Release entitled, “Yale Test Detects Early Stage Ovarian Cancer With 99% Accuracy,” dated February 13, 2008 (citing source as Clinical Cancer Research Journal 14 (4) February 15, 2008.) ]

There Is Always Hope — Just Ask Sean Swarner!

Sean Swarner’s ESPN Segment

“CLIMB EVERY MOUNTAIN IN LIFE,” by Sean Swarner.

“I’m actually the first (and only) cancer survivor to summit the world’s highest mountain … Mt. Everest. When I was only 13, I was diagnosed with Hodgkin’s disease and given three months to live. When I was 15, I was diagnosed with Askin’s Sarcoma. The prognosis was much worse as the doctors gave me only two weeks to live. Again, I survived. …

Being the only person in the world to have ever had these two cancers, I really felt I should share my story to help motivate others and influence lives. On May 16th, 2002 at 9:32am, I became the first cancer survivor to summit Mt. Everest.

Since then, I have been lucky enough to reach the summits of three more of the world’s seven highest peaks and have spoken internationally about my life and adventures to countless people and organizations. On the summit of Everest I brought a flag adorned with names of people who have been affected by cancer and left it on the top of the world forever commemorating the struggle of cancer patients worldwide.

I did the same to the highest point in Africa, Europe and just recently returned from 23,000-foot Aconcagua in South America! My ultimate goal is to climb the highest mountain on each continent AND trek to the North and South poles.

… The reason for these expeditions is to inspire those affected by cancer (as well as anyone with a pulse!) to dream big and never give up. ”

Sean Swarner was the recipient of the “Don’t Ever Give Up Award” presented by the Jimmy V Foundation and ESPN in 2007. Sean told ESPN Radio’s Bob Valvano, brother of Jimmy, that he would have been more likely to win the lottery four or five times with the same numbers than to have survived both cancers.

Sean did survive and achieved this monumental feat with only one fully functioning lung due to removal of a golf ball sized tumor (and the lung in which it was embedded) as part of his Askin’s diagnosis. He graduated from high school in 1993. To date, Sean has climbed the “Seven Summits” of the world — the tallest mountain peaks located on each of the seven continents — and provides hope and inspiration to thousands if not millions of people living with cancer. Sean’s ultimate goal is to complete the “Explorer’s Grand Slam” — Seven Summits, North and South Geographical Poles and North and South Magnetic Poles. To date, only four other individuals accomplished this feat.

Sean established his own foundation known as “The Cancer Climber Association,” which promotes cancer awareness and helps raise money for cancer research. He also authored “Keep Climbing,” which is the title of his book that recounts his story and journey from the depths of his near death experience to the peaks that he climbed to reach the top of the world 17 years later.

If you were recently diagnosed with ovarian cancer, do not let anyone tell you that there is no hope. Just ask Sean Warner!