The standard of practice for women with Stage III ovarian cancer has changed, as new data confirm the major survival benefit associated with combined intravenous and intraperitoneal chemotherapy after optimal surgical debulking of tumor, according to an article in the January 5 issue of the New England Journal of Medicine and a statement by the National Cancer Institute (USA).

The current study showed that patients who received combination postoperative chemotherapy had a median survival time 16 months longer than women who received intravenous chemotherapy alone.

The study, conducted by Deborah K. Armstrong, MD, an assistant professor at the Johns Hopkins Kimmel Cancer Center in Baltimore, Maryland, and her colleagues, builds upon evidence from eight other clinical trials ? including those conducted at Memorial Sloan-Kettering Cancer Center? showing an overall survival period of approximately one year for women treated with intraperitoneal chemotherapy after optimal debulking surgery.

Based on this overwhelming evidence, the National Cancer Institute issued a clinical announcement on January 5 encouraging the administration of combination chemotherapy to treat women with advanced ovarian cancer who have undergone optimal surgical debulking.

The National Cancer Institute clinical announcement to surgeons and other medical professionals was made with the support of six professional societies and advocacy groups. It coincided with publication in the New England Journal of Medicine of the results of a large clinical trial by Deborah Armstrong, M.D., medical oncologist and an associate professor at Johns Hopkins Kimmel Cancer Center in Baltimore, Md., and her colleagues in an NCI-supported research network known as the Gynecologic Oncology Group (GOG).

The current trial involved 429 women with stage III ovarian cancer who were given chemotherapy following the successful surgical removal of tumor. It compared two treatment regimens: 1) intravenous paclitaxel followed by intravenous cisplatin, with intravenous paclitaxel followed by intraperitoneal cisplatin and subsequent administration of intraperitoneal paclitaxel.

"Intraperitoneal therapy is not a new treatment approach, but it has not been widely accepted as the gold standard for women with ovarian cancer," said Armstrong. "There has been a prejudice against intraperitoneal therapy in ovarian cancer because it's an old idea, it requires skill and experience for the surgery and for the chemotherapy, and it's more complicated than intravenous chemotherapy. But now we have firm data showing that we should use a combination of intraperitoneal and intravenous chemotherapy in most women with advanced ovarian cancer who have had successful surgery to remove the bulk of their tumor."

Standard treatment for women with stage III ovarian cancer has been surgical removal of the tumor (debulking), followed by six to eight courses of intravenous chemotherapy given every three weeks with a platinum drug such as cisplatin or carboplatin and a taxane drug such as paclitaxel. The new National Cancer Institute clinical announcement recommends that women with advanced ovarian cancer who undergo effective surgical debulking receive combination chemotherapy.

Intraperitoneal chemotherapy allows higher doses and more frequent administration of drugs, and it appears to be more effective in killing cancer cells in the peritoneal cavity, where ovarian cancer is likely to spread or recur first.

“In our trial, women who received part of their chemotherapy via an intraperitoneal route had a median survival time 16 months longer than women who received only intravenous chemotherapy,” said Armstrong. The 205 women treated via the intraperitoneal route fared better, even though most of them received fewer than the six planned treatments.

Complications associated with the abdominal catheter used to deliver intraperitoneal chemotherapy were the main reason only 86 of the women completed all six treatments. Women who received intraperitoneal chemotherapy had more side effects than those treated with intravenous chemotherapy alone, but most side effects were temporary and easily managed. One year after treatment, women in both study groups had the same reported quality of life.

More studies are needed to determine the best intraperitoneal drug regimen and the optimal number of such treatments. Future trials also will address how to reduce toxicity associated with intraperitoneal administration.

An estimated 22,220 women in the United States were diagnosed with ovarian cancer in 2005. It causes more deaths in the United States than any other cancer of the female reproductive system, with an estimated 16,210 women dying from the disease in 2005. The most recent statistics show that only 45 percent of women survive five years after being diagnosed with ovarian cancer; the rate increases to 94 percent when the disease is diagnosed before it has spread. However, women with ovarian cancer frequently have no symptoms or only mild symptoms until the disease is advanced. As a result, only 19 percent of all cases are detected at that early, localized stage.

The clinical announcement regarding treatment for advanced ovarian cancer is available online at http://ctep.cancer.gov/highlights/ovarian.html.