NCI Urges IV/IP Chemo for Advanced Ovarian Cancer

BETHESDA, Maryland-In a clinical announcement, the National Cancer Institute (NCI), supported by six professional societies and advocacy groups, has urged physicians to use a combination of intravenous (IV) and intraperitoneal (IP) chemotherapy to treat women with advanced ovarian cancer. In the announcement, the first NCI has issued since 1999, the institute said the two techniques used together extend overall survival for advanced ovarian cancer patients by about 1 year.

The NCI announcement noted that eight trials have evaluated the use of chemotherapy delivered into the abdomen for ovarian cancer and that "together, these trials show a significant improvement in survival for women with advanced ovarian cancer."

The standard therapy for stage III ovarian cancer has been surgical removal of the tumor, followed by six to eight courses of IV chemotherapy given every 3 weeks with a platinum drug, usually cisplatin or carboplatin, and a taxane, either pac-litaxel or docetaxel (Taxotere).

NCI now recommends that women with advanced disease who successfully undergo 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," the Institute said.

The new recommendation has the backing of the Gynecologic Oncology Group (GOG), Society of Gynecologic Oncologists, Oncology Nursing Society, Society of Gynecologic Nurse Oncolo-gists, Gynecologic Cancer Foundation, and Ovarian Cancer National Alliance.

The statement's release coincided with the publication of results from a large clinical trial (GOG-172) conducted by medical oncologist Deborah Armstrong, MD, of the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, and her colleagues. Their findings appeared in the January 5, 2006, issue of the New England Journal of Medicine (354:34-43, 2006).

Prejudice Against IP Therapy

"IP is not a new treatment approach, but it has not been widely accepted as the gold standard for women with ovarian cancer," Dr. Armstrong said. "There has been a prejudice against IP therapy in ovarian cancer because it’s an old idea, it requires skill and experience for the surgery and or the chemotherapy, and it’s more complicated than IV chemotherapy. But 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."

The NCI announcement said that "the best data sources suggest that less than 1% of women with ovarian cancer receive IP chemotherapy."

Randomized Trial

The randomized, multicenter trial led by Dr. Armstrong (GOG-172) involved 429 previously untreated stage III ovarian cancer patients who were randomized to two groups for treatment following successful surgery, which the protocol defined as no visible disease or no tumor greater than 1 cm in size following the debulking operation.

One arm received the standard regimen of IV paclitaxel at 135 mg/m2 over 24 hours followed on day 2 by 75 mg/m2 of IV cisplatin. The second group received 135 mg/m2 of IV paclitaxel over 24 hours followed by IP cisplatin at 100 mg/m2 on day 2, and the subsequent IP administration of paclitaxel at 60 mg/m2 on day 8. Treatment for both arms was administered every 3 weeks for up to six courses.

Previous studies comparing IP to IV chemotherapy did not include paclitaxel. The primary goal of GOG-172 was to determine "whether the improvement in survival noted with IP treatment in other studies was still seen when paclitaxel was given with a platinum drug," NCI said.

Although most of the 205 women in the IP group received fewer than the protocol's six planned treatments, they fared significantly better than the women in the comparison arm. "In our trial, women 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," Dr. Armstrong said.

One year after treatment, women in the two study arms reported the same quality-of-life level. However, women treated with IP chemotherapy experienced more adverse events than those in the IV-only group, including abdominal pain, nausea, and vomiting, as well as hematologic, metabolic, and neurologic toxicities.

Most of the side effects were temporary or easily managed. However, complications associated with the abdominal catheter, particularly infection and fever, were common in the IP-treated patients and were the major reason only 86 women (42%) in the group completed the planned six IP courses of chemotherapy.

"Randomized, multicenter clinical trials, including this most recent study, clearly show the value of IP chemotherapy-an extended life for women with advanced ovarian cancer," said GOG chairman Philip DiSaia, MD, professor and director of the Division of Gynecologic Cancer at the University of California, Irvine.

For more information on NCI's recommendation, go to http://ctep.cancer.gov/highlights/ovarian.html.