Frontline Winter 2013 

Recurrent Ovarian Cancer:

Ovarian cancer is a relatively rare disease, but it is the most lethal of all gynecologic malignancies and the fifth most common cause of cancer death in women. About 22,300 women were expected to be diagnosed with the disease in the United States in 2012.

By DAVID E. COHN, MD, director of the Division of Gynecologic Oncology, professor of Obstetrics and Gynecology and the Gertrude Parker Heer Chair in Cancer Research

Lacking a reliable screening test, 60 percent of ovarian cancer cases have distant metastases and a five-year survival of 27 percent at diagnosis.

Overall tumor response rates to standard therapy (paclitaxel and carboplatin) are relatively high at 70 to 80 percent, but 50 to 70 percent of responders relapse within about 18 months, and recurrent disease remains incurable.

Nonetheless, we have made progress against the disease over the last decade or so. More effective therapies for primary ovarian cancer have increased median survival to about five years after diagnosis, up from 12 to 18 months a decade ago.

In addition, more drugs are available to treat recurrent disease. Ten to 20 years ago, recurrent ovarian cancer was fatal within months because few therapies were available. Today, there are many more, including those the FDA has approved for treatment of the disease and others that are used "off label," enabling some patients to live for years with stable disease.

Given the options for treatment, ovarian cancer is considered by many to be a chronic disease that is treated somewhat like hypertension. Controlling refractory hypertension begins by prescribing a particular medication, and if that one doesn't work a second or third is tried. The goal is to hit on a drug that matches well with the patient's inherent response to blood pressure medication and might be used to maintain it until the drug ceases working. Similarly, ovarian cancer is typically treated with a number of drugs and regimens that produce a response for a few months, then lose effectiveness. Different agents are tried until, hopefully, one is found that matches well with the cancer's biology and provides therapy that allows the patient to be progression-free and feeling well for years.

Despite the successes in the treatment of ovarian cancer, patients who experience recurrence generally die of their disease after multiple treatment regimens. The OSUCCC - James Gynecologic Oncology program is engaged in clinical and translational research to improve the treatment and outcomes of women with recurrent ovarian cancer.

For example, we are conducting a national phase II study investigating a novel clinical agent called Reolysin. This is a non-genetically modified oncolytic (i.e., cancer-cell killing) virus that is prevalent in the community.

We completed a phase I study of the agent at Ohio State a few years ago, the first to use intravenous and intraperitoneal Reolysin in ovarian cancer. We showed that intravenous delivery led to viral replication in ovarian tumors present in the abdomen. This showed that it wasn't necessary to inject the virus directly into the tumor to achieve cancercell death, which was the previous strategy used in other types of cancers treated with Reolysin.

The outcome of that trial led to the current randomized, phase II Gynecologic Oncology Group trial, GOG 0186H ( identifier: NCT01199263), for which I am principal investigator.

The trial will ultimately accrue 110 patients.

"It is our hope that identification of specific cancer-causing pathways and their potential treatments will lead to therapies that prolong survival, cause fewer side effects and improve outcomes - including quality of life - for women with ovarian cancer."

The study randomizes women with recurrent ovarian cancer to weekly paclitaxel or to paclitaxel plus intravenous Reolysin. The primary outcomes are response rate and survival.

We also have translational researchers investigating potential biomarkers and molecular pathways involved in ovarian cancer with the goal of developing targeted therapies to treat the disease. Selvendiran Karuppaiyah, PhD, in the Division of Gynecological Oncology, for example, is helping to design a drug that targets the STAT3 pathway, which is important in ovarian cancer. The drug is in laboratory and preclinical testing now, and it could begin phase I testing in the near future.

These studies are examples of the research needed to improve the treatment of ovarian cancer. While there have been substantial improvements in the outcomes of women with recurrent ovarian cancer, the fact that most women with the disease end up dying of their cancer highlights the importance of continued clinical, translational and basic research. It is our hope that identification of specific cancer-causing pathways and their potential treatments will lead to therapies that prolong survival, cause fewer side effects and improve outcomes - including quality of life - for women with ovarian cancer.

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