Giving intraperitoneal (IP) chemotherapy along with intravenous (IV) chemotherapy can improve survival of women with Stage III ovarian cancer by more than a year, according to a recent study. The results, which appeared in the New England Journal of Medicine (2005;354:34–43), prompted the National Cancer Institute (NCI) to issue a clinical announcement encouraging use of this approach for appropriate patients.
“IP chemotherapy allows higher doses and more frequent administration of drugs, and it appears to be more effective at killing cancer cells in the peritoneal cavity, where ovarian cancer is likely to spread or recur first,” the NCI said in a statement preceding the clinical announcement.
Although IP chemotherapy has been around for decades, it has not been widely used, said the lead author of the NEJM study, 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 Johns Hopkins Kimmel Cancer Center in Baltimore. “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.”
Armstrong's study included 210 women assigned to six cycles of standard IV chemotherapy with cisplatin and paclitaxel, and 205 women assigned to six cycles of both IV and IP chemotherapy with cisplatin and paclitaxel. The women all had Stage III ovarian cancer that had been optimally debulked, with no residual masses larger than 1 cm.
Women in the IP group had longer progression-free survival (about 23 months versus 18 months for IV chemotherapy, P = 0.05) and lived longer overall. Women who had only IV chemotherapy survived a median of 49.7 months, whereas those who got IP and IV chemotherapy had a median survival of 65.6 months (P = 0.03).
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. Cannistra is 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. Although the number of treatment-related deaths was similar in both groups (five in the IV-IP group versus four in the IV-only group), women who got IP treatment had many more Grade 3 or 4 side effects, including leukopenia, infection, fatigue, and pain. Many of these side effects were related to the abdominal catheters. These problems were so serious that only 42% of the women assigned to receive IP chemotherapy completed all six planned treatment cycles. That makes the survival improvement seen in this trial that much more remarkable, Cannistra wrote.
Women who got IP therapy reported significantly worse quality of life during and just after treatment, but both groups reported similar quality of life 1 year after completion of treatment.
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.
Other experts agree with NCI's action.
“I think NCI has wisely brought this treatment approach, which has been limited in use, to everyone's attention by recommending it be used to treat late-stage ovarian cancer,” said Carolyn Runowicz, MD, National Volunteer President of the American Cancer Society (ACS) and Professor of Obstetrics and Gynecology, Division of Gynecologic Oncology, at the University of Connecticut School of Medicine.
But Armstrong's study also raises many questions about IP chemotherapy that can only be answered by conducting further clinical trials, added Runowicz, who is also Director of the Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center in Farmington.
We still must learn which drugs work best with IP chemotherapy, how many IP treatments and what schedule 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. Finding the optimal catheter design to use with IP chemotherapy will be key.
Runowicz 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.”