According to Julian Schink, MD, chief of gynecologic oncology at Chicago’s Northwestern Memorial Hospital, “Women diagnosed with ovarian cancer today live an average of five times longer than women affected by the disease 30 years ago due to significant advances in how we detect and treat ovarian cancer, as well as increased awareness of symptoms that are associated with ovarian cancer.”

Warning Signs

Diagnosing ovarian cancer is difficult because there is currently no reliable screening test. In addition, there were no officially recognized symptoms associated with ovarian cancer until 2007, when the Gynecologic Cancer Foundation, Society of Gynecologic Oncologists, and American Cancer Society issued a statement formally noting the following:

* Bloating

* Pelvic or abdominal pain

* Difficulty eating or feeling full quickly

* Urinary symptoms (urgency or frequency)

Doctors stress that the frequency and number of symptoms are key and that women who experience a combination of these symptoms almost daily for two to three weeks should see their doctor. “Patients should listen to their bodies, be assertive and tell their doctor if a change occurs. It’s important to investigate symptoms thoroughly in order to catch ovarian cancer early,” says Schink.

Reducing Your Risk

One in 55 women will develop ovarian cancer in her lifetime and the risk increases for women who are genetically predisposed. However, Schink notes there are steps you can take to lower your risk:

* Oral contraceptives—women who use birth control pills for at least five years are three times less likely to develop ovarian cancer.

* Tubal ligation—permanent forms of birth control such as tubal ligation reduce the risk of ovarian cancer by 50 percent.

* Removal of ovaries—women with an extensive family history of breast or ovarian cancer, or who carry altered versions of the BRCA genes, may opt for a prophylactic oophorectomy to remove both ovaries, lowering the risk of ovarian cancer by up to 80 percent.

Treatment

While difficult to detect, specialized centers such as the Northwestern Ovarian Cancer Early Detection and Prevention Program, a collaborative effort between the hospital and the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, have strategies for monitoring women at risk. Patients are monitored with ultrasound and blood tests every six months. “The goal of the program is to catch cancer that may develop early, so patients can receive treatment before it reaches an advanced stage,” says Schink. “Studies show that patients who go to a center of excellence committed to treating ovarian cancer have better outcomes and a greater chance that their cancer will be successfully removed.”

Treatment for ovarian cancer includes surgery to remove the ovaries, uterus and tissues that ovarian cancer often spreads to, the appendix and, in some cases, lymph nodes in the pelvic region. Doctors at Northwestern Memorial also use a form of chemotherapy called intraperitoneal chemotherapy, which is injected directly into the abdominal cavity and has been linked to a 15-month improvement in survival.

When asked about the future of ovarian cancer, Schink states he is encouraged by the progress that has been made and that with new drugs, treatments and surgical strategies on the horizon, he is optimistic. “The best scenario would be to prevent this cancer entirely. Until that day comes, we will continue to aggressively seek the best treatment and provide the highest level of care possible to our patients.”

By: Northwestern Memorial Hospital – Tue, 09/09/2008 – 13:22

Ovarian cancer accounts for about 3% of all cancers among women and ranks 2nd among gynecological cancers. It causes more deaths than any other cancer of the female reproductive system.

In 2005, 538 Michigan women died from ovarian cancer, and in 2004, 727 Michigan women were newly diagnosed with the disease. In 2008, the American Cancer Society estimates that 550 Michigan women will die from ovarian cancer.

There are many risk factors for developing ovarian cancer. The risk factors that increase a woman’s risk for the disease include:

- Family history of ovarian or breast cancer

- Personal history of breast cancer

- White/Caucasian race

- Being of Ashkenazi Jewish descent

- Older age

- Early menarche (before age 12) or late menopause (after age 50)

- Never having had children

- Having children late in life

- High fat diet

- Use of talcum powder on the genital area

Factors that reduce a woman’s risk for developing ovarian cancer:

- Use of birth control pills

- Having more than one child

- Breast feeding

- Having a hysterectomy (removal of the uterus) or tubal ligation (female sterilization)

- Having both ovaries removed

“Because there currently is no effective screening test for this disease, ovarian cancer usually is not diagnosed at an early stage,” said Greg Holzman, chief medical executive for the Michigan Department of Community Health.

However, recent studies have shown that the following symptoms are more likely to occur in women with ovarian cancer than women in the general population:

- Bloating

- Pelvic or abdominal pain

- Difficulty eating or feeling full quickly

- Urinary symptoms (urgency or frequency)

“If you have these symptoms occur almost daily and with increasing severity for more than a few weeks, you should see your doctor, preferably a gynecologist, for a thorough examination,” Holzman said.

By: Michigan Department Of Community Health – Wed, 09/10/2008 – 16:20

On an intent-to-treat (ITT) basis for the 125 enrolled patients, the median progression-free survival (PFS) was 5.6 months on the Telcyta plus PLD arm compared to 3.7 months on the PLD control arm, p = 0.7243 and hazard ratio (HR) = 0.92. The study did not meet the statistical significance p less than or equal to 0.05. The overall response rate as measured by RECIST was 12%, including one complete response (CR) for the Telcyta plus PLD arm and 8% for the PLD control arm.

Of the 125 patients in the ITT population, a prespecified analysis was conducted for 75 patients with platinum refractory or primary platinum resistant disease, including 40 patients on the Telcyta plus PLD arm and 35 patients on the PLD control arm. The median PFS of these patients was 5.6 months for the Telcyta plus PLD arm compared to 2.9 months for the PLD control arm, p = 0.0425 and HR = 0.55. The response rate, as assessed by RECIST, was 15%, including one CR for the Telcyta plus PLD arm and 6% for the PLD control arm.

The initial trial design provided for the enrollment of 244 patients. The trial was interrupted by a brief clinical hold, followed by a partial clinical hold from June 2007 until October 2007. At the time of the clinical hold, 125 patients had been enrolled in the trial. Although enrollment was permitted after the release of the clinical hold, Telik decided not to enroll additional patients, a decision which impacted the powering of the study.

The 125 patients randomized to the trial were well-balanced for patient demographics and key ovarian cancer disease characteristics. Telcyta was administered at 1000 mg/m2 followed by PLD at 50 mg/m2, the approved dose of PLD, every 28 days. Thirty-five patients were not able to complete their assigned per-protocol therapy and discontinued due to the clinical hold, including 21 patients on the Telcyta plus PLD arm and 14 patients on the PLD control arm.

There was a higher incidence of hematologic adverse events (AEs) in patients on the Telcyta plus PLD arm (66%) versus 44% on the PLD arm. The hematologic toxicities were manageable with dose reductions and growth factor support on both treatment arms.

The most common, non-hematologic adverse events, including nausea, fatigue, vomiting, and constipation, were similar in incidence and severity on both arms. Seventeen percent Grade 2 and 3 stomatitis and 9% Grade 2 and 3 palmar-plantar erythrodysesthesia (PPE) were observed on the Telcyta plus PLD arm, compared to 23% Grade 2 and 3 stomatitis and 21% Grade 2 and 3 PPE on the PLD control arm. Grade 4 PPE (2%) was only observed on the PLD control arm. Telcyta may ameliorate the incidence and severity of stomatitis and PPE known to be associated with PLD.

By: Telik, Inc. – Thu, 10/30/2008 – 07:31

“The early detection of ovarian cancer is the Holy Grail,” says lead investigator Dr. David E. Cohn, a gynecologic oncologist and researcher at The Ohio State University Comprehensive Cancer – James Cancer Hospital and Solove Research Institute.

“Too many women die from ovarian cancer because it often is detected too late, when the prognosis is poor. We are trying to use a blood test to detect ovarian cancer earlier, when the prognosis is better.”

In 2008, an estimated 20,000 women will be diagnosed with ovarian cancer, and more than 15,000 will succumb to the disease.

The findings are published in the journal Gynecologic Oncology. First author Dr. Kimberly Resnick also presented the findings at an international meeting on molecular markers in cancer in Hollywood, Fla.

“We can clearly define the microRNA pattern in the blood of patients with this disease,” Cohn says. These findings could have implications for other cancers, as well, he says.

MicroRNAs (miRNAs) are single-stranded RNA molecules that help regulate the proteins made by cells. MiRNAs are smidgens of genetic material measured in a few nucleotides of length. A gene, in comparison, can be tens of thousands of nucleotides long.

“We hypothesized that there would be a different miRNA expression between the blood of patients with ovarian cancer and those without, and our study supported the hypothesis,” says Resnick, who is a gynecologic oncology fellow and researcher at Ohio State’s Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute.

The study of 28 ovarian cancer patients and 15 cancer-free women found that patients who have ovarian cancer have a certain pattern of miRNAs in their blood that is similar to the pattern of miRNAs found in the tumors from patients with ovarian cancer, Cohn says. The control group without ovarian cancer lacked this specific pattern of miRNAs in their blood.

“Further study is needed, but we are hoping that one day this could become a standard screening test for ovarian cancer, similar to the PSA screening now routinely offered for men to detect prostate cancer,” says Cohn. “But just like any test, we must validate it in larger studies, so such a test is years away from being commercially available on the market.”

Cohn, Resnick and fellow collaborator Dr. Carlo M. Croce, who is the director of human cancer genetics at Ohio State, have applied for a patent on developing this technology as a screening blood test for ovarian cancer.

The CA-125 blood test measures the level of a protein released by ovarian cancer cells. That protein is known as a tumor marker because it is usually present at higher levels in women with ovarian cancer. CA-125 is most commonly used to detect recurrent ovarian cancer in women who have been previously treated.

However, the CA-125 level can be elevated in men and women who do not have cancer and only half of patients with early stage, curable ovarian cancer will have an elevated CA-125 level. In addition, 25 percent of patients who have ovarian cancer will register a normal CA-125 blood test level, Cohn says.

Although CA-125 testing is helpful for monitoring a patient’s response to treatment, this test alone cannot diagnose ovarian cancer, nor is it effective in screening healthy women for ovarian cancer. A high level of CA-125 can also be due to causes other than cancer, he says. These include inflammatory conditions of the abdomen; recent surgery; gynecologic conditions such as fibroids, endometriosis or ectopic pregnancy; or a ruptured cyst.

Ovarian cancer is difficult to diagnose because there is no reliable screening test available, says Resnick. Symptoms of ovarian cancer may include bloating; pelvic or abdominal pain; difficulty eating or feeling full quickly; or urinary symptoms of frequency or urgency.

“Unfortunately, right now we have poor screening tools for this disease, and 80 percent of the time the disease is diagnosed at an advanced stage,” says Resnick. “We need a screening test that can identify this disease at an earlier stage and identify patients who are at risk for developing this disease.”

By: Ohio State University Medical Center – Wed, 11/12/2008 – 06:38

The research team also found that expression of the protein, known as PEA-15, is an independent indicator of a woman’s prospects for surviving ovarian cancer, said senior author Naoto T. Ueno, M.D., Ph.D. associate professor of breast medical oncology.

An analysis of ovarian cancer tumors from 395 women showed those with high expression of the PEA-15 had a median survival time of 50.2 months compared with 33.5 months for women with low levels of the protein in their tumors.

“These findings provide a foundation for developing a PEA-15 targeted approach for ovarian cancer and for clarifying whether this protein is a novel biomarker that can predict patient outcomes,” Ueno said.

Ovarian cancer kills about 15,000 women in the United States annually, and is notoriously hard to diagnose in its early stages, when it is also most optimal to treat.

A series of lab experiments by first author Chandra Bartholomeusz, M.D., Ph.D., showed that high expression of PEA-15 inhibits the growth of ovarian cancer cells by killing cells via autophagy, or self-cannibalization, rather than by apoptosis. Removing PEA-15 from ovarian cancer cells led to a 115 percent increase in the number of cells compared with a control group of cells that still had the protein.

In apoptosis, defective cells die from self-induced damage to their nuclei and DNA complex. Autophagy kills when a cell entraps parts of its cytoplasm in membranes and digests the contents, leaving a cavity. When this goes on long enough, the cell essentially eats itself until it dies, its cytoplasm riddled with cavities.

Location, location, location

Ueno’s research team has found that the protein works to inhibit cancer in two distinct ways depending on its location in the cell.

First, PEA-15 inhibits one of the prominent actors in the growth, differentiation and mobility of cells, a protein called extracellular signaling related kinase, or ERK. Activated ERK in the cell nucleus fuels cancer growth. The research team earlier found that PEA-15 binds to ERK in the nucleus and moves it out into the cytoplasm, preventing its growth effects.

Now they’ve found that PEA-15 in the cytoplasm induces autophagy in cancer cells, a second method of inhibiting cancer growth. “These two very different actions by PEA-15 are based on the location of the protein,” Ueno said.

ERK is an inviting target for cancer therapy, Ueno noted, but so far no one has been able to develop a successful ERK inhibitor.

“PEA-15 offers us a new dimension for potentially targeting ERK,” Ueno said. “We’ve shown with high levels of PEA-15, women with ovarian cancer are surviving longer.” Levels of the protein in tumors also might affect how other drugs work against the disease. Similar research is under way in breast cancer with. PEA-15, which is short for phospho-enriched protein in astrocytes.

By: University of Texas M. D. Anderson Cancer Center – Sun, 11/16/2008 – 05:34

The compounds could be less harmful than current cancer treatments on the market such as cisplatin and carboplatin because they don’t penetrate the cell nucleus and attach to DNA, said lead author Rathindra Bose. Conventional drugs can interfere with the functions of the cell’s enzymes, which lead to side effects such as hearing and hair loss and kidney dysfunction.

Though scientists don’t fully understand the mechanism by which the phosphaplatins kill cancer cells, they suspect that the compounds bind to the cell surface membrane proteins and transmit a “death signal” to the interior of the cell, Bose said. The compounds are created by attaching platinum to a phosphate ligand, which can readily anchor to the cell membrane. Future studies will focus on identifying the exact process.

“The findings suggest a paradigm shift in potential molecular targets for platinum anticancer drugs and in their strategic development,” said Bose, a professor of biomedical sciences and chemistry and vice president for research at Ohio University who conducted the work while at Northern Illinois University.

The first drug developed for the treatment of ovarian and testicular cancers, cisplatin, was approved for use in 1982. Though it’s 95 percent effective, it works best during the early stages of the disease, and some patients develop a resistance to it. Two drugs introduced later, carboplatin and oxaliplatin (which is used for colorectal cancer), overcame some of those problems, but their potency can harm the immune system of patients, said Bose, who has been studying alternative compounds and targets for these cancers for 25 years.

Phosphaplatins have the potential to be more efficient, more targeted and create fewer side effects in the patient, Bose said. The new study shows that the phosphaplatins can kill ovarian cells at half of the dosage of conventional drugs, but are just as potent. Unlike cisplatin, which can decompose quickly and create additional toxic side effects through the decomposition products, the new compounds show no signs of degradation after seven days, he added.

A U.S. patent is pending on the work; two provisional patents have been filed. Bose and his colleagues next will test the compounds in mice models.

Co-authors of the study are Leila Maurmann of Kansas State University, and Robert Mishur, Linda Yasui, Shefalika Gupta, W. Scott Grayburn, Heike Hofstetter and Tara Milton, all of Northern Illinois University.

By: Ohio University – Wed, 11/19/2008 – 16:16

The prospective study was presented by Professor Ignace B. Vergote of University Hospital Leuven, EU, on behalf of the European Organization for Research and Treatment of Cancer-Gynaecological Cancer Group (EORTC-GCG) and the National Cancer Institute Canada-Clinical Trial Group (NCIC-CTG).

A total of 718 patients from 60 institutions with advanced ovarian cancer were enrolled in the study. The women were randomized to receive either primary debulking surgery (PDS) prior to receiving six cycles of chemotherapy (329 patients as per protocol), or interval debulking surgery (IDS) performed after three of six cycles of neoadjuvant chemotherapy (339 patients as per protocol). The current treatment guidelines for stage IIIc and IV disease recommend debulking surgery prior to administering chemotherapy. This study represents the first randomized phase III neoadjuvant clinical trial ever reported for ovarian cancer treatment.

“Most women diagnosed with ovarian cancer have advanced stage disease. Surgery before chemotherapy is not a practical course of treatment for patients in many countries because of difficulty scheduling surgery for patients with extensive cancer and associated complications,” said the study’s author, Prof. Vergote. “Because of this trend in treatment, our trial was designed to validate the administration of chemotherapy prior to surgery. In addition to establishing acceptability for this strategy, our study demonstrates fewer complications when chemotherapy is administered prior to surgery.”

The median follow-up for all participants was 4.8 years. Overall survival and progression free survival were similar in both arms of the study, but a statistically significant reduction in complications, including postoperative deaths (2.7 percent in PDS versus .6 percent in IDS) was observed. The PDS arm of the study demonstrated a higher rate of hemorrhage (7 percent versus 1 percent) and blood clots (2.4 percent versus .3 percent).

“It was concluded that in patients with very extensive disease, as included in our study, neoadjuvant chemotherapy followed by interval debulking surgery can be considered as the preferred treatment. However, chemotherapy before surgery should not be used in patients with less than FIGO stage IIIc ovarian cancer, or small IIIc ovarian cancers, as these patients were not well-represented in the study” said Prof. Vergote. “Aggressive debulking surgery to no residual tumor remains the most important prognostic factor, underscoring the importance of a maximal surgical effort whenever the surgery is performed, whether the surgery is performed before or after chemotherapy.”

Worldwide, nearly 200,000 women are diagnosed of ovarian cancer each year and every year, over 100,000 women die of the disease.

By: Fox Chase Cancer Center – Wed, 12/03/2008 – 15:54

Obesity affects health in several ways, but new research shows obesity can have minimal impact on ovarian cancer survival. A study by researchers at the University of Alabama at Birmingham (UAB) Comprehensive Cancer Center found ovarian cancer survival rates are the same for obese and non-obese women if their chemotherapy doses are closely matched to individual weight.

The findings contradict earlier research that shows obese women have lower ovarian cancer survival rates compared to non-obese patients. In the UAB study, such survival disparity disappeared when chemo doses were calculated by actual body weight rather than a different dosing standard, said Kellie Matthews, M.D., a UAB gynecologic oncologist and lead author on the new study.

“Often chemotherapy dosing is calculated using ‘ideal’ body weight as a guide. We found using actual body weight works best, and it wipes away much of the difference in survival rates between obese and non-obese patients,” Matthews said.

The results are published online in the journal Gynecologic Oncology.

Researchers reviewed the medical records of 304 patients diagnosed with an aggressive form of the disease called epithelial ovarian cancer. Patients were of similar cancer stage and grade, and all had surgery followed by chemo.

The analysis showed that when actual body weight was used in chemo dosing the overall survival is 40 months for non-obese patients and 47 months for obese patients, not a significant difference, Matthews said. Similar outcomes are seen in obese and non-obese cancer survivors being monitored for recurrence of their ovarian cancer.

UAB’s chemo dosing formula includes actual weight, body mass index (BMI) and other factors, Mathews said. Obesity is defined as a BMI (BMI: kg/m2) of 30 or more.

The study authors acknowledged that while it was possible to follow this formula and remove obesity as a negative indicator for ovarian cancer survival, obesity still puts women at increased risk for complications related to cancer surgery, such as greater blood loss and stubborn-to-heal incisions. Also, research shows obese women are more likely to have other health problems such as diabetes and cardiovascular disease that may impact cancer treatment.

By: University of Alabama at Birmingham – Mon, 12/29/2008 – 14:53

Compounds in cranberries may help improve the effectiveness of platinum drugs that are used in chemotherapy to fight ovarian cancer, researchers have found in a laboratory study. The scientists demonstrated in cell culture studies that human ovarian cancer cells resistant to platinum drugs became up to six times more sensitized to the drugs after exposure to the cranberry compounds in comparison to cells that were not exposed to the compounds, which were obtained from juice extracts.

Although preliminary, the findings have the potential to save lives and reduce the harmful side effects associated with using high doses of platinum drugs for the treatment of ovarian cancer, the researchers say, adding that human studies are still needed. The new study adds to a growing number of potential health benefits linked to cranberries.

“For the first time, we have shown in our in vitro studies that cranberry extracts can sensitize resistant human ovarian cancer cell lines, say Ajay P. Singh, Nicholi Vorsa, and colleagues. “This has opened up exciting possibilities for therapeutic intervention associated with platinum therapy.

By: American Chemical Society – Wed, 08/22/2007 – 15:17

The American Cancer Society, Gynecologic Cancer Foundation and the Society of Gynecologic Oncologistsin June announced recommendations for identifying symptoms that couldsignal the early stages of ovarian cancer. Experts from the groupscalled on women who experience the symptoms — which include bloating,pelvic or abdominal pain, difficulty eating or feeling full quickly,and a frequent or urgent need to urinate — every day for two to threeweeks to see a gynecologist.

According to the specialists, womenwho have the symptoms should visit a gynecologist for a pelvic andrectal exam. If the exams suggest a possibility of ovarian cancer, thenext step would be a transvaginal ultrasound and a blood test to detectCA125, a substance that is often elevated in women who have ovariancancer (Kaiser Daily Women’s Health Policy Report, 6/14). According to the Globe and Mail,20% of women in the Canadian survey believed the CA125 test is used toscreen for ovarian cancer, but it actually is used to mark ovariancancer tumors.

"It is critical that young women know that theHPV vaccine and Pap tests for cervical cancers are not catchalls fordiseases below the waist," Barbara Vanderhyden, the Corinne Boyer chairin ovarian cancer research at the University of Ottawa,said. Vanderhyden added that she is concerned many girls and youngwomen will believe gynecological exams are not necessary if they havereceived an HPV vaccine. Ross said that the best way for women todetect ovarian cancer is to be aware of the symptoms.

An estimated 2,400 Canadian women will be diagnosed with ovarian cancer this year, and 1,700 will die of the disease, the Globe and Mail reports (Globe and Mail, 9/4).

Reprinted with permission from kaisernetwork.org. You can view theentire Kaiser DailyWomen’s Health Policy Report, search the archives, and sign up for emaildelivery at kaisernetwork.org/email. The Kaiser Daily Women’s Health Policy Report is published for kaisernetwork.org, afree service of The Henry J. Kaiser Family Foundation. 2007 Advisory BoardCompany and Kaiser Family Foundation. All rights reserved.

By: Kaisernetwork.org – Wed, 09/05/2007 – 16:47