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Summary: A large clinical trial shows that giving chemotherapy directly into the abdomen, as well as into a vein, can improve survival of women with advanced ovarian cancer by about 16 months. The results of the study, which appear in this week's issue of the New England Journal of Medicine, prompted the National Cancer Institute to issue a statement encouraging doctors to use this approach for appropriate patients.

Why it's important: Ovarian cancer is the fourth leading cause of cancer deaths in women, striking more than 22,000 women and killing more than 16,000 in 2005. Although this disease is very treatable when caught early, most cases (about 80%) are not found until they have spread beyond the ovaries. Because so many ovarian cancer patients are diagnosed at a later stage, it's important to find ways to improve treatments for more advanced disease.

What's already known: Most women with advanced ovarian cancer get chemotherapy after surgery to remove the tumor. That chemotherapy is usually given into a vein and travels through the bloodstream to reach tumor cells in the abdomen. Doctors have also experimented with giving the chemotherapy directly into the abdomen through a catheter, a technique called intraperitoneal (IP) chemotherapy. Eight clinical trials of this approach have been done, and most showed a benefit to IP chemotherapy. But this technique isn't widely used, according to the study's lead author, Deborah Armstrong, MD.

"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 for the chemotherapy, and it's more complicated than IV chemotherapy," said Armstrong, who is a medical oncologist and associate professor at the John Hopkins Kimmel Cancer Center in Baltimore.

How this study was done: Women with stage III ovarian cancer were randomly assigned to get either standard chemotherapy in a vein (210 women), or a combination of chemotherapy in a vein and IP chemotherapy (205 women). The women had already had surgery that successfully removed all or most of the tumor; none had tumors remaining that were larger than 1 cm in diameter. All the women were treated with the same drugs, cisplatin and paclitaxel. Six cycles of chemotherapy were planned for both groups.

What was found: Women who received IP chemo went longer without their cancer coming back (about 23 months vs. 18 months for traditional chemotherapy) and lived longer overall. Women who had traditional chemotherapy in a vein survived about 4 years after treatment, while those who got chemotherapy in the abdomen as well as a vein survived an average of nearly 5 ½ years after treatment.

That improvement is "one of the largest benefits ever observed for a new therapy in gynecologic oncology," according to Stephen A. Cannistra, MD, who wrote an editorial published with the study. He is a professor at Harvard Medical School and director of the division of gynecologic medical oncology at Beth Israel Deaconess Medical Center in Boston.

However, the IP treatment was much harder on the patients. Women who got this treatment had many more severe or life-threatening side effects, including low white blood cell counts, infection, fatigue, and pain. Many side effects were related to the catheters that must be inserted into the abdomen to deliver the chemotherapy. These problems were so serious that fewer than half of the women assigned to receive IP chemotherapy completed all 6 planned treatment cycles. That makes the survival improvement that much more remarkable, Cannistra wrote.

Women who got IP therapy also reported significantly worse quality of life during and just after treatment. By one year out, however, both groups reported similar quality of life.

The bottom line: Although the side effects were serious, the National Cancer Institute said the results of this study, combined with those of previous research, are enough to warrant recommending IP chemotherapy to eligible women.

"IP chemotherapy allows higher doses and more frequent administration of drugs, and it appears to be more effective at killing cancer cells in the [abdominal] cavity, where ovarian cancer is likely to spread or recur first," the NCI stated in its announcement.

But there's still more work to be done to improve IP treatments, NCI and the study authors said. Doctors must learn which drugs work best with IP chemo, how many IP treatments are needed to be effective, and whether women with earlier stage cancer also would benefit from IP therapy. It is also important to look for ways to reduce the side effects the treatment causes without compromising its effectiveness.

Those questions can only be answered by clinical trials, said American Cancer Society president Carolyn Runowicz, MD, a gynecological oncologist who is experienced with IP chemotherapy. She said women who want IP treatment for ovarian cancer should either enroll in a clinical trial or get one of the regimens that have been proven to increase survival, like the one described in this study.

"I think we're making marked advances in the understanding of cancer that will translate into better therapies, so if you can stay alive longer, you have a better chance of getting one of these new treatments in the pipeline," she said. "If it were me, I'd choose IP therapy as the initial therapy, since this study showed such a marked improvement in survival."

Citations: "Intraperitoneal Cisplatin and Paclitaxel in Ovarian Cancer." Published in the Jan. 5, 2006, New England Journal of Medicine (Vol. 354, No. 1: 34-43). First author: Deborah K. Armstrong, MD, of the Johns Hopkins Kimmel Cancer Canter, Baltimore.

"Intraperitoneal Chemotherapy Comes of Age." Published in the Jan. 5, 2006, New England Journal of Medicine (Vol. 354, No. 1: 77-79). Author: Stephen A. Cannistra, MD, of Beth Israel Deaconess Medical Center and Harvard Medical School, Boston.