NATIONAL CANCER INSTITUTE SUGGESTS CHANGES IN TREATMENT OF ADVANCED OVARIAN CANCER 
UMass Medical School faculty participated in national clinical trial of intravenous and intraperitoneal chemotherapy; results published in New England Journal of Medicine 

January 4, 2006 

WORCESTER, Mass.-The National Cancer Institute (NCI), part of the National Institutes of Health, today issued an announcement encouraging treatment with anticancer drugs via two methods, after surgery, for women with advanced ovarian cancer. The combined methods, which deliver drugs into a vein and directly into the abdomen, were shown in a large, randomized, multi-center clinical trial to extend overall survival for women with advanced ovarian cancer by about a year. UMass Memorial Medical Center participated in the multi-site, NCI-supported clinical trial, which studied 429 women with ovarian cancer.

"This finding will change the treatment standard for care of women with ovarian cancer," said Harrison G. Ball, MD, chief of gynecologic oncology at UMass Memorial Medical Center and professor of obstetrics and gynecology at the University of Massachusetts Medical School. "The survival rates for women with advanced ovarian cancer are not good; through this study, however, we've found that by delivering chemotherapy both intravenously and intra-peritoneally-directly into the abdominal cavity-we can help women survive up to 12 months longer. To a cancer patient, a year is very important."

In 2005, more than 22,000 women in the United States were diagnosed with ovarian cancer, the leading cause of reproductive system cancer deaths in women; more than 16,000 women died of the disease. In part because women with ovarian cancer frequently show no symptoms or mild symptoms until the disease is advanced, only 19 percent of cases are detected at the early, localized stage, and only 45 percent of women survive five years after diagnosis. Conversely, if the disease is detected before it has spread, the five-year survival rate increases to 94 percent.

The NCI's clinical announcement to surgeons and other medical professionals was made with the support of six professional societies and advocacy groups. The announcement coincides with publication in the January 4, 2006, New England Journal of Medicine of the results of a large clinical trial by medical oncologist Deborah Armstrong, MD, 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). This is the eighth trial evaluating the use of chemotherapy delivered into the abdomen for ovarian cancer. Together, these trials show a significant improvement in survival for women with advanced ovarian cancer.

The two treatment methods are called intravenous, or IV, for chemotherapy delivered into a vein and intraperitoneal, or IP, for chemotherapy delivered into the abdominal, or peritoneal, cavity. The trial involved women with stage III ovarian cancer who were given chemotherapy following the successful surgical removal of tumors. It compared two treatment regimens: 1) IV paclitaxel followed by IV cisplatin to 2) IV paclitaxel followed by IP cisplatin and the subsequent administration of IP paclitaxel.  The UMass Memorial arm of the trial was conducted from 1998 to 2001.

IP chemotherapy, although not a new treatment approach, has not been widely accepted in part because it is more complicated than traditional IV chemotherapy and requires greater skill and experience for the surgery and for the chemotherapy. According to study director Dr. Armstrong, however, "Now we have firm data showing that we should use a combination of IP and IV 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, followed by six to eight courses of IV chemotherapy given every three weeks with a platinum drug, such as cisplatin or carboplatin, and a taxane drug, such as paclitaxel. Platinum and taxane are two classes of anticancer drugs. The new NCI clinical announcement recommends that women with advanced ovarian cancer who undergo effective surgery receive a combination of IV and IP chemotherapy. IP 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.

Women in Armstrong's trial who received part of their chemotherapy via an IP route had a median survival time 16 months longer than women who received only IV chemotherapy. The 205 women treated via the IP route fared better, even though most of them received fewer than the six planned treatments. Complications associated with the abdominal catheter used to deliver the IP chemotherapy were the main reason only 86 of the women completed all six IP treatments. Women who received IP chemotherapy had more side effects than those treated with IV 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.   

According to the NCI, more studies are needed to determine the best IP drug regimen and the optimal number of IP treatments. Future trials also will address how to reduce toxicity associated with IP administration. In addition to continued research to improve ovarian cancer treatment, NCI is funding studies to identify disease markers and develop improved screening techniques, enabling earlier detection and treatment of the disease.

"Americans look to NCI-and to all of the institutes that constitute the National Institutes of Health-for unbiased research studies and sound counsel. This clinical announcement is a demonstration of that commitment," said NIH Director Elias A. Zerhouni, MD.

Additional information on IP chemotherapy, including administration, as well as other resources for clinicians and patients can be obtained at http://www.gog.org, http://onsopcontent.ons.org/Toolkits/Chemotherapy/and http://www.ons.org/patientEd/Treatment/chemotherapy.shtml.

For more information about cancer, please visit the NCI Web site at http://www.cancer.govor call NCI's Cancer Information Service at 1-800-4 CANCER (1-800-422-6237).

Contact: Alison Duffy, 508-856-2000