Tag Archives: ovarian cancer

Epirubicin Improves Overall Survival Better Than Ifosfamide When Combined with Paclitaxel and Cisplatin

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Epirubicin (Ellence®) produced longer median overall survival (OS) than ifosfamide (Ifex®) in a recent phase II randomized clinical trial comparing (i) cisplatin, paclitaxel and ifosfamide, with (ii) cisplatin, paclitaxel and epirubicin, in newly diagnosed advanced epithelial ovarian cancer patients. In this trial, patients with histologically proven epithelial ovarian cancer were randomly assigned to receive first-line polychemotherapy with cisplatin/paclitaxel/epirubicin (CEP arm) or cisplatin/paclitaxel/ifosfamide (CIP arm) for six cycles every 21 days. Two hundred and eight patients were randomised between the two treatment arms. The Phase II clinical trial finds were as follows:

  • After a median follow-up of 82 months, median overall survival (OS) was 51 months in the CIP arm, and 65 months in the CEP arm; and
  • 5-year survival rates were 43% in the CIP arm, and 50% in the CEP arm.

The trial investigators note that the OS findings seem longer in duration than is commonly reported, especially considering that more than 50% of the newly diagnosed advanced ovarian cancer patients were suboptimally debulked or cytoreduced after their first surgery. The trial investigators concluded that this unexpected finding might be a consequence of the close surgical surveillance and aggressive chemotherapeutic approach.

[Source: “A phase II randomised clinical trial comparing cisplatin, paclitaxel and ifosfamide with cisplatin, paclitaxel and epirubicin in newly diagnosed advanced epithelial ovarian cancer: long-term survival analysis;” Fruscio R. et. al.; Br J Cancer. 2008 Feb 26;98(4):720-7.]

Comment: Although small in size, this Phase II randomized clinical trial suggests that aggressive surgical intervention followed by aggressive polychemotherapy (involving epirubicin or ifosfamide in tandem with paclitaxel and cisplatin) may increase overall survival in newly diagnosed, advanced-stage ovarian cancer survivors. The findings of at least one major clinical study cite that optimal cytoreduction, as a stand-alone independent factor, provides up to a 50% increase in actuarial survival. In the U.S., an “optimal” cytoreduction is generally defined as a surgical procedure that results in 1 centimeter or less of macroscopic cancer present within the body after surgery. The surprising results of the study discussed above seem to indicate that a suboptimal cytoreduction or debulking surgery followed by aggressive polychemotherapy may be beneficial in extending overall survival in newly diagnosed, advanced-stage ovarian cancer survivors. The issue of what measure should be used to define an “optimal” cytoreduction or debulking is not without controversy with the ovarian cancer arena.

Avastin Used in Combination with Taxol and Paraplatin Will Become the Clinical Gold Standard Treatment by 2011

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“Avastin Used in Combination with Taxol and Paraplatin Will Become the Clinical Gold Standard Treatment by 2011, According to a New Report from Decision Resources

WALTHAM, Mass., April 23 /PRNewswire/ — Decision Resources, one of the world’s leading research and advisory firms focusing on pharmaceutical and healthcare issues, finds that surveyed oncologists say that a therapy’s effect on overall survival is the attribute that most influences their prescribing decisions in advanced ovarian cancer. Clinical data and expert opinion show that Roche/Genentech/Chugai‘s Avastin (bevacizumab) plus the regimen of paclitaxel (Bristol-Myers Squibb’s Taxol, generics) and carboplatin (Bristol- Myers Squibb’s Paraplatin, generics) has advantages in this attribute over the combination of paclitaxel/carboplatin, the current sales leader in ovarian cancer treatment.

The new report entitled Ovarian Cancer (Advanced): Therapies Must Increase Survival over Paclitaxel/Carboplatin to Successfully Enter this Generic Market finds that, according to surveyed oncologists, a drug that offers improved median overall survival compared with paclitaxel/carboplatin would earn a 50 percent patient share in the ovarian cancer market. Surveyed oncologists indicated that they would prescribe Avastin plus paclitaxel/carboplatin to 29 percent of their patients with advanced ovarian cancer. As a result, Avastin plus paclitaxel/carboplatin will earn a 22 percent patient share in the U.S. advanced ovarian cancer market in 2016.

The report also finds that Avastin plus paclitaxel/carboplatin will earn the clinical gold-standard status for treatment of advanced ovarian cancer in 2011, following its approval for the indication in 2010. Surveyed oncologists indicated that Avastin plus paclitaxel/carboplatin has competitive advantages in efficacy over paclitaxel/carboplatin, the current gold standard.

‘Avastin plus paclitaxel/carboplatin has the same delivery attributes and only marginally different safety attributes when compared with paclitaxel/carboplatin,’ said Jenna Avent, analyst at Decision Resources. ‘However, the regimen of Avastin plus paclitaxel/carboplatin has better efficacy when compared to the current gold standard, paclitaxel/carboplatin, and oncologists rate efficacy as the most important parameter in the treatment of advanced ovarian cancer.’”

[Quoted Source:  “Avastin Used in Combination with Drugs from Bristol-Myers Squibb Has Advantages in Survival Rates Over the Current Sales-Leading Therapy for Advanced Ovarian Cancer,” News, EarthTimes.org, April 23, 2008][Emphasis added].

Ovarian Cancer Developments Presented at the 2008 Annual AACR Meeting

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I have set forth below a list of several significant ovarian cancer developments that were presented at the 2008 Annual Meeting of the American Association For Cancer Research (AACR) held on April 12 – 16, 2008 in San Diego, California.

“I’m Strongs to the Finish, ‘Cause I Eats Me Spinach”* — Popeye May Have It Right When It Comes to Ovarian Cancer Prevention

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“Brigham and Women’s Study Finds Eating a Flavonoid-Rich Diet Helps Women Decrease Risk of Ovarian Cancer –Findings from the Nurses’ Health Study

Boston, MA – New research out of the Channing Laboratory at Brigham and Women’s Hospital (BWH) reports that frequent consumption of foods containing the flavonoid kaempferol, including non-herbal tea and broccoli, was associated with a reduced risk of ovarian cancer. The researchers also found a decreased risk in women who consumed large amounts of the flavonoid luteolin, which is found in foods such as carrots, peppers and cabbage. These findings appear in the November 15, 2007 issue of the International Journal of Cancer.

‘This is good news because there are few lifestyle factors known to reduce a woman’s risk of ovarian cancer,’ said first author Margaret Gates, ScD, who is a research fellow at BWH. “Although additional research is needed, these findings suggest that consuming a diet rich in flavonoids may be protective.”

The causes of ovarian cancer are not well understood. What is known is the earlier the disease is found and treated, the better the chance for recovery; however, the majority of cases are diagnosed at an advanced (metastasized) stage after the cancer has spread beyond the ovaries. According to the National Cancer Institute, the 5-year relative survival rate for women diagnosed with localized ovarian cancer is 92.4 percent. Unfortunately, this number drops to 29.8 percent if the cancer has already metastasized.

In this first prospective study to look at the association between these flavonoids and ovarian cancer risk, Gates and colleagues calculated intake of the flavonoids myricetin, kaempferol, quercetin, luteolin and apigenin among 66,940 women enrolled in the Nurses’ Health Study. In this population, 347 cases of epithelial ovarian cancer were diagnosed between 1984 and 2002.

Although total intake of these five common dietary flavonoids was not clearly beneficial, the researchers found a 40 percent reduction in ovarian cancer risk among the women with the highest kaempferol intake, compared to women with the lowest intake. They also found a 34 percent reduction in the risk of ovarian cancer among women with the highest intake of luteolin, compared to women with the lowest intake.

‘In this population of women, consumption of non-herbal tea and broccoli provided the best defense against ovarian cancer,’ concluded Gates, who is also a research fellow at the Harvard School of Public Health. ‘Other flavonoid-rich foods, such as onions, beans and kale, may also decrease ovarian cancer risk, but the number of women who frequently consumed these foods was not large enough to clearly evaluate these associations. More research is needed.’

The National Cancer Institute funded this research.”

[Quoted Source: “Brigham and Women’s Study Finds Eating a Flavonoid-Rich Diet Helps Women Decrease Risk of Ovarian Cancer — Findings from the Nurses’ Health Study,” Brigham and Women’s Hospital Press Release, dated November 13, 2007 (citing findings from “A prospective study of dietary flavonoid intake and incidence of epithelial ovarian cancer;” Gates, M.A. et. al.; International Journal of Cancer, Volume 121, Issue 10, Pages 2225 – 2232 (November 15, 2007))].

Comment: In addition to spinach, foods richest in kaempferol include tea (nonherbal), onions, curly kale, leeks, broccoli, and blueberries.

* In 1933, Max and Dave Fleischer’s Fleischer Studios adapted Thimble Theatre characters into a series of Popeye the Sailor theatrical cartoon shorts for Paramount Pictures. These cartoons proved to be among the most popular of the 1930s, and the Fleischers-and later Paramount’s own Famous Studios-continued production through 1957. Since then, Popeye has appeared in comic books, television cartoons, a 1980 live-action film (Popeye, directed by Robert Altman), arcade and video games, and hundreds of advertisements and peripheral products.

Early references to spinach in the Fleischer cartoons and subsequently in further stories of Popeye are attributed to the publication of a study which, because of a misprint, attributed to spinach ten times its actual iron content. The error was discovered in the 1930s but not widely publicized until T.J. Hamblin wrote about it in the British Medical Journal in 1981. Until that time, the popularity of Popeye helped boost sales of the leafy vegetable 33% in the U.S.

“The Truth About Cancer,” Airs April 16th on PBS

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The Truth About Cancer on PBS -- Airs April 16th

Avax Technologies Announces Initiation of Clinical Study With Autologous Ovarian Cancer Vaccine

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“AVAX Technologies, Inc. (OTC Market:AVXT.OB) today announces it has received FDA approval to begin enrollment into a Phase I-II clinical trial of OVax® for patients with advanced, chemotherapy-refractive ovarian cancer. [For a copy of the clinical trial inclusion/exclusion criteria refer to “OVax®: A Feasibility Study Using a DNP-Modified Autologous Ovarian Tumor Cell Vaccine as Therapy in Ovarian Cancer Patients After Relapse.”]. The study will be performed in collaboration with Cancer Treatment Centers of America, Inc (CTCA). It will be centered in the CTCA hospital in Zion, Illinois, although patients also will be referred from other CTCA hospitals in Tulsa and Philadelphia, and its out-patient clinic in Seattle.

Up to 42 eligible patients with stage III or IV ovarian carcinoma will be enrolled. These patients’ cancers will have progressed despite initial surgery and chemotherapy and failed to respond to one or two salvage chemotherapy regimens. They will undergo debulking surgery, and tumor tissue will be sent to AVAX for production of vaccine. Post-operatively, they will receive intraperitoneal chemotherapy with a taxane and then will be enrolled into the protocol.

Three doses of OVax will be tested, and each of the three doses will be analyzed for immunological efficacy with the goal of optimizing the dose for treatment of patients in future trials.

‘We are enthusiastic about receiving FDA clearance to start this important clinical trial and with the opportunity it affords us to collaborate with CTCA,’ stated Dr. David Berd, Chief Medical Officer of AVAX. ‘Clearly, better treatments for ovarian cancer are needed and we hope that OVax will eventually find its place as a relatively non-toxic therapeutic alternative for these patients. This alliance with CTCA will allow us to expand the therapeutic utility of the AC Vaccine platform along with our ongoing Phase I/II program in non-small cell lung cancer and our recently launched Phase III pivotal registration study in melanoma (MVALDI).’

As part of the business collaboration CTCA has made an up-front payment of $250,000 and will begin to make monthly payments of $25,000 upon the initiation of production of vaccines at AVAX’s Philadelphia manufacturing facility.

‘We are very excited to be part of a new chapter in the fight against ovarian cancer,’ said Dr. Edgar Staren, Chief Medical Officer at Cancer Treatment Centers of America. ‘Ovarian cancer is a very complex cancer that is often resistant to chemotherapy, radiation and surgery. At Cancer Treatment Centers of America, our commitment to cancer patients is to help fight their cancer with the most advanced medical technology available. This partnership with AVAX gives hope to ovarian cancer patients who are told far too often that there is nothing more that can be done for them. This treatment option will work well with our unique integrative care model that combines state-of-the-art traditional medicine with scientifically-based complementary therapies such as aggressive nutritional management and support, naturopathic medicine, physical therapy, mind-body medicine and spiritual support to go beyond treating the tumor and supporting the needs of the whole person – all under one roof.’

About the AC Vaccine Therapeutic

The AC Vaccine is an immunotherapy prepared by attaching a small chemical to the patient’s tumor cells in a process known as haptenization. This hapten modification allows the tumor cells to stimulate a T cell-based immune response to a patients own tumor cells. An early indicator of T cell immune activity is Delayed Type Hypersensitivity (DTH).

An understanding of what AVAX calls the immunopharmacology of the AC Vaccines is critical to their effective use. AVAX believes that the optimal dose, schedule of administration, and route of administration of human cancer vaccines must be established before they enter advanced phase studies, and that some competing vaccine technologies have failed because their developers ignored one or more of these parameters in early phase development. The optimum schedule and best route of administration (intradermal) to be used for OVax were determined by extensive phase I-II studies of MVax. The latest phase I-II trial was completed last year and the results will be presented at the 2008 [Annual] meeting of the American Society of Clinical Oncology (ASCO).”

[Quoted Source: “AVAX Technologies Announces Initiation of Clinical Study with Autologous Ovarian Cancer Vaccine (OVax®),” BusinessWire news release dated April 9, 2008.]

Comment: The OVax®vaccine clinical trial carries great promise. The trial will combine three potent approaches to battling ovarian cancer: (i) debulking surgery, (ii) intraperitoneal chemotherapy with a taxane drug, and (iii) a custom made vaccine created from the ovarian cancer survivor’s own tumor. Please watch the video below regarding the OVax® vaccine for ovarian cancer.

We Have Met the Enemy and He is Us* — But Not If Aethlon Medical Has Its Way!

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Why can’t the human body immune system prevent all cancers? Because the immune system generally does not identify ordinary human cells — an essential building block of the human body — as a threat to the body, notwithstanding that such cells may possess an uncontrolled level of proliferation. To the extent that the immune system recognizes that certain cancer cells are “suspicious,” solid cancer tumors (including ovarian) further inhibit the attack capability of the immune system by secreting so-called “exosomes.”

Normally, immune system cells known as “T-cells” are entrusted with killing foreign invaders that may be harmful to the body. Exosomes secreted by ovarian cancer cells prevent the “expression” or activation of two biological markers (i.e., Jak-3 kinase & CD3-zeta) which must be present as a prerequisite for T-cell activation. Generally, the biological markers Jak-3 kinase and CD3-zeta are highly expressed in activated T-cell lines. When T-cells are subjected to ovarian cancer ascites fluid, the critical Jak-3 kinase and CD3-zeta biological markers are consistently absent. In sum, the exosomes secreted by ovarian cancer cells produce immunosuppressive activity within the human body and allow the cancer cells to avoid destruction by causing T-cell inactivation. The immunosuppressive activity associated with ovarian cancer is known to correlate with disease progression and reduced long-term survival.

Aethlon Medical, Inc., a pioneer in developing medical devices to treat infectious disease, developed a device known as the “Hemopurifier®” which is capable of removing immunosuppressive exosomes from ovarian cancer cell fluid, thereby allowing proper activation of immune system T-cells that are capable of killing cancer cells. In follow-on studies, Dr. Douglas Taylor at the University of Louisville demonstrated that the capture of exosomes by the Hemopurifier(R) resulted in reversing immunosuppressive activity (i.e., eliminate exosomes). Throughout the course of the studies, the Aethlon Hemopurifier® completely removed the immunosuppressive activity normally found in the ascites fluid of ovarian cancer patients.

Prior to conducting the follow-on studies mentioned above, Dr. Taylor documented that 60% of circulating exosomes were removed from the blood of ovarian cancer patients during the first pass (approximately 10-minutes) through a small scale Hemopurifier®. The capture data was consistent over the course of five different studies. Exosomes are released by solid tumors, lymphomas, and leukemia. Because exosomes induce T-cell apoptosis (programmed cell death), and block T-cell signaling, proliferation, and cytokine production, high concentrations of circulating exosomes correlate with reduced T-cell production and tumor progression in cancer patients. The ability to reduce the presence of circulating exosomes could reverse immune suppression and increase patient responsiveness to both immunotherapy and chemotherapy. As such, Aethlon believes that the Hemopurifier(R) addresses a significant unmet medical need in cancer care.

Dr. Taylor is a recognized authority on the causative effects of immune suppression in cancer patients. He is credited with the initial characterization of exosomes and is a leading peer reviewed author on the subject. Aethlon disclosed that Dr. Taylor did not receive nor request any compensation for conducting the research studies mentioned above.

“Based on emerging data, we envision the Hemopurifier(R) will become a treatment standard that enhances the benefit of therapies administered to those who suffer from cancer,” stated James A. Joyce, Chairman and CEO of Aethlon Medical.

Aethlon Medical Company Background

“Aethlon Medical is the developer of the Hemopurifier®, a first-in-class medical device to treat infectious disease. The Hemopurifier® addresses the largest opportunity in infectious disease, the treatment of drug and vaccine resistant viruses. The Hemopurifier(R) is a single use extracorporeal device that converges hollow-fiber filtration technology with immobilized affinity agents to capture viruses and soluble glycoproteins from the blood. The device has been designed to mimic the natural immune response of clearing infectious viruses and immunosuppressive proteins from circulation. Regulatory and commercialization initiatives in the United States are focused on bioterror threats, while international initiatives are directed towards naturally evolving pandemic threats, and chronic infectious disease conditions including Hepatitis-C (HCV) and the Human Immunodeficiency Virus (HIV). Collaborative studies to demonstrate utility of the Hemopurifier(R) are being conducted with researchers at the Government of India’s National Institute of Virology (NIV), The U.S. Centers for Disease Control and Prevention (CDC), The United States Army Medical Research Institute of Infectious Diseases (USAMRIID), and The Southwest Foundation for Biomedical Research (SFBR). Aethlon recently demonstrated safety of the Hemopurifier(R) in a 24-treatment human study and is now conducting follow-on safety studies at the Fortis Hospital in Delhi, India. The Company has also submitted an Investigational Device Exemption (IDE) to the U.S. Food and Drug Administration (FDA) related to advancing the Hemopurifier(R) as a broad-spectrum treatment countermeasure against category “A” bioterror threats. Additional information regarding Aethlon Medical and its Hemopurifier(R) technology can be accessed online at www.aethlonmedical.com.”

[Post Source and Quoted Post Source: “The Aethlon Hemopurifier(R) Reverses Immune Suppression in Cancer,” Aethlon Medical, Inc. News Release dated November 19, 2007].

*[Post Title Source: The “foreword” chapter of The Pogo Papers, written by Walt Kelly and published by Simon & Schuster (Paper) (June 1953). The complete Kelly foreword chapter quote (which is a paraphrase of a message sent in 1813 from U.S. Navy Commodore Oliver Hazard Perry to Army General William Henry Harrison after The Battle of Lake Erie stating “We have met the enemy, and they are ours”) is “There is no need to sally forth, for it remains true that those things which make us human are, curiously enough, always close at hand. Resolve then, that on this very ground, with small flags waving and tinny blast on tiny trumpets, we shall meet the enemy, and not only may he be ours, he may be us.” Walt Kelly first used the abbreviated quote “We Have Met The Enemy and He Is Us” on a poster for Earth Day in 1970.]

CNN Reports On the Hemopurifier®

Five Years Later, Patient Participating in Vaccine Trial Remains Free of Ovarian Cancer

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“Like most women with ovarian cancer, 44-year-old Christine Sable of Lancaster, Pennsylvania, did not discover she had the disease until it was in the advanced stages and had spread to other areas of the abdomen. ‘I knew my chances of recurrence were very high-75 to 80 percent at that particular stage-and that the disease would likely recur within a year or two,’she says. ‘Once it recurs, it is difficult to cure.’

After aggressive surgery and chemotherapy, the only other option her doctor could offer was more chemotherapy. But the first round had been ‘very hard,’ Sable recalls. ‘I wanted to find something that would work with my own immune system and not be so harsh on my body.’

Then she learned about a Phase I clinical research study of an ovarian cancer vaccine developed by Kunle Odunsi, MD, PhD, Surgeon in Gynecologic Oncology and Co-Leader of the Tumor Immunology and Immunotherapy Program at Roswell Park [Cancer Institute]. The vaccine is designed to trigger an immune response in the significant number of women who have tumors that test positive for the antigen NY-ESO-1.

The study was open to patients who had completed their initial treatments and who had no further evidence of disease; Sable fit the profile. She says the day she was accepted into the study was ‘one of the most exciting days of my life.’ She began treatment at Roswell Park in February 2004, and her immune system responded so strongly to the first five doses of vaccine that she received another five, then another five, each time experiencing a better response-with no side effects. Now 49 and still cancer-free, she returns to Roswell Park just once a year for continued monitoring.

Odunsi is currently leading a team of Roswell Park researchers who are working to improve the vaccine’s effectiveness. The vaccine is an important new focus in the search for better treatments for ovarian cancer, which is often difficult to treat. Sable says participating in the trial ‘was a very good experience; I was very well cared for. Dr. Odunsi is a gentle, kind man, brilliant and dedicated and very compassionate.’ In May of 2008, Sable will mark the fifth anniversary of her diagnosis and survival. ‘To have had this many years cancer-free is really amazing.’

The study in which she participated was supported by the Cancer Vaccine Collaborative Program of the Cancer Research Institute and Ludwig Institute for Cancer Research, and results were reported in the … [NY-ESO-1 Peptide Vaccine Phase I Clinical Trial Results, Odunsi, K et. al., Proceedings of the National Academy of Sciences, Vol. 141, no 31, July 31, 2007].” [Quoted Source: Science Daily News Release dated April 7, 2008.]

In March 2008, The Ovarian Cancer Research Fund (OCRF) awarded a $900,000 research grant to Dr. Odunsi and his colleagues at the Roswell Park Cancer Institute (RPCI) to fund a collaborative study with the stated goal of developing a promising vaccine to unleash the power of the immune system against cancer. The prestigious award will allow Dr. Odunsi and the RPCI research team to combine four different immunotherapy approaches, all designed to enhance the immune system’s response to ovarian cancer. [Source: “Roswell Park Cancer Institute awarded three-years funding for ovarian cancer vaccine,” a News-Medical.Net News Release dated April 7, 2008.]

Comment: Vaccine or immunotherapy can play an important role in an ovarian cancer survivor’s overarching treatment strategy. This aspect of treatment is often overlooked. It is important to be aware of the availability of vaccine therapy as early as possible in treatment because most clinical trials utilizing vaccine therapy require an extremely low disease “tumor burden” or no (macroscopic) evidence of disease as a prerequisite for patient eligibility. Low tumor burden or no evidence of disease is generally present immediately after chemotherapy treatment(s) resulting in “complete remission,” and/or surgery resulting in “optimal debulking/cytoreduction.” Christine Sable is an excellent example of an ovarian cancer survivor who is proactively managing her care through enrollment in a beneficial clinical trial.

The Roswell Park Cancer Institute, as of this writing, is currently recruiting Stage II through IV ovarian cancer participants for a Phase II vaccine clinical trial involving the use of “Recombinant Vaccinia-NY-ESO-1 (rF-NY-ESO-1) and Recombinant Fowlpox-NY-ESO-1 (rF-NY-ESO-1) in Patients With Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma Whose Tumors Express NY-ESO-1 or LAGE-1 Antigen.” For more information with respect to this clinical trial, contact the Roswell Park Cancer Institute Clinical Trials Office at 877-275-7724.

I encourage you to watch the video segment below which addresses Christine Sable’s case, including an interview with Kunle Odunsi, M.D., Ph.D.., the Co-Leader of the Tumor Immunology and Immunotherapy Program at Roswell Park.

MediaSourceTV Video Segment Re

Christine Sable and Roswell Park Cancer Institute Clinical Trial Vaccine Program

Is It Possible to Have Ovarian Cancer at a Young Age?

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The ovarian cancer survivor highlighted this week is Maddie Kullen. Mattie is different from virtually all other ovarian cancer survivors because she was diagnosed with the disease when she was 6 years old. Upon diagnosis, Maddie had a 6-inch tumor removed at Children’s Hospital Boston, followed by 16 weeks of chemotherapy. Maddie’s treatments are now over and she is cancer-free.

If you think a 6 year old cannot make a difference in the fight against ovarian cancer, you are absolutely wrong. Maddie is a spokesperson for Ovations for the Cure and participated in that group’s ovarian cancer awareness public service announcement. Maddie was also part of the Boston Marathon Jimmy Fund Walk. Her best idea was the creation of a program at Children’s Hospital Boston that provides young cancer patients with an ice cream break each week. This program is called “Sundaes on Saturday,” and it is supported by monies raised through Kullen family fundraisers. Please take time to watch Maddie’s ovarian cancer awareness public announcement below and visit Ovations for the Cure if you are interested in finding out more about the mission of that group.

When asked by a WBZTV Boston journalist to comment on her appearance in the Ovations for the Cure ovarian cancer awareness spot, Maddie simply responded, “Cool! And then once I saw the commercial I went back to watching kid shows.”

Comment: Although Maddie’s ovarian cancer diagnosis represents an extremely rare case, it is important to note that ovarian cancer does not discriminate when it comes to age, race or financial status. For more information regarding the early warning signs and symptoms of ovarian cancer, visit the H*O*P*E* blog page entitled, “Warning Signs and Symptoms.”

Maddie Kullen in Ovations For the Cure Ovarian Cancer Public Service Announcement

NOV-002 and Carboplatin Slow Disease Progression of Platinum Drug Resistant Ovarian Cancer

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“Novelos Therapeutics, Inc. (OTCBB: NVLT), a biopharmaceutical company focused on the development of therapeutics to treat cancer and hepatitis, today announced continued encouraging results in an ongoing Massachusetts General Hospital Cancer Center and Dana-Farber/Harvard Cancer Center (DF/HCC) Phase 2 trial of NOV-002 in combination with carboplatin in platinum-resistant ovarian cancer patients. Fifteen patients have now been enrolled and, to date, 60% (9) have had slower than expected disease progression. NOV-002 was well-tolerated, further extending the excellent safety profile NOV-002 has demonstrated in previous studies. Detailed results of this trial will be presented as a poster at the 2008 annual meeting of the American Society of Clinical Oncology (ASCO) taking place May 30 – June 3 in Chicago, Illinois.

‘I am encouraged by these results in platinum-resistant ovarian cancer, with NOV-002 (in combination with carboplatin) apparently slowing disease progression in over half of the treated patients. Most women who have failed three lines of chemotherapy would be expected to progress in about eight weeks. I am excited to present the trial results at ASCO,’ said Dr. Carolyn Krasner, medical oncologist at the Massachusetts General Hospital Cancer Center and the Principal Investigator. ‘We look forward to working closely with Dr. Krasner, the Massachusetts General Hospital Cancer Center, Dana-Farber/Harvard and other institutions on designing and implementing a larger NOV-002 trial for this indication,’ said Harry Palmin, President and CEO of Novelos. ‘Our objective is to commence the next Phase 2 trial in platinum-resistant ovarian cancer in early 2009.’

According to the American Cancer Society, in 2007 approximately 22,000 U.S. women were diagnosed with ovarian cancer and 15,000 women were expected to die from it. There is a lack of effective treatment, particularly in the case of platinum-resistant patients. Once a woman’s ovarian cancer is defined as platinum-resistant the chance of having a partial or complete response to further platinum therapy is typically less than 10% and only 10-20% with other available agents. Thus, there is a major unmet medical need for this indication. …”

[Source: “Novelos Therapeutics Announces Continued Encouraging Results in Ongoing Phase 2 Ovarian Cancer Trial at Dan-Farber/Harvard Cancer Center;” Novelos Therapeutics, Inc. Press Release dated March 31, 2008.]

2008 SGO Annual Meeting Ovarian Cancer Abstract Highlights

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The Society of Gynecologic Oncologists (SGO) held its “Women’s Cancer” annual meeting on March 9-12th in Tampa, Florida. I have provided below links to several DG Dispatch and medpage Today news releases that summarize important SGO meeting abstracts and presentations:

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

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“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

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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

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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!

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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