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The newspaper of The Johns Hopkins University January 9, 2006 | Vol. 35 No. 16
Abdominal Chemo Boosts Survival in Ovarian Cancer Patients

Deborah Armstrong, associate professor at the Johns Hopkins Kimmel Cancer Center, and Robert Bristow, director of the Johns Hopkins Ovarian Cancer Center.

Hopkins-led study suggests new treatment standard for advanced disease

By Vanessa Wasta
Johns Hopkins Medicine

A 50-year-old method for delivering chemotherapy directly into the abdomen is making a comeback as investigators have found that it increases survival — by more than a year — in some women with advanced ovarian cancer.

Results from a seven-year study of more than 400 patients nationwide are published in the Jan. 5 issue of the New England Journal of Medicine.

Investigators randomly grouped women with newly diagnosed stage III ovarian cancer into two categories: those who would get all chemotherapy intravenously and those who would get chemotherapy both intravenously and through a catheter inserted directly into the abdomen.

"The catheter allows us to bathe the entire abdominal area with a high concentration of chemotherapy for a long period of time, which appears to be better at destroying lingering cancer cells," said Deborah Armstrong, associate professor at the Johns Hopkins Kimmel Cancer Center and principal investigator for the study, which was conducted by the Gynecologic Oncology Group. While the main site for ovarian cancer spread is the abdominal area, Armstrong said that the intravenous round of chemotherapy is needed to catch cancer cells that may have spread outside the abdomen.

Overall survival for 205 patients receiving abdominal (or intraperitoneal) chemotherapy in the study was an average of 65.6 months, a 25 percent improvement over the intravenous-only group of 210 patients, whose average was 49.7 months. Similarly, relapse-free survival for those receiving intraperitoneal chemo was 23.8 months compared with 18.3 months for the intravenous-alone group, a 20 percent improvement.

"This is a significant improvement in survival for women with this disease, which is most often diagnosed at an advanced stage," Armstrong said.

Side effects, such as suppressed blood counts and neurological problems, were significantly worse for the group receiving intraperitoneal, or IP, chemotherapy. They reported poorer quality of life during their treatment. However, investigators noted that one year later, patients in the IP group were on par with those getting only intravenous chemo. Nine patients died due to complications of the treatments, five from receiving IP chemotherapy and four from intravenous.

With these study results, the team of investigators, supported by the national Gynecologic Oncology Group, now can recommend IP therapy as the new standard for many women with ovarian cancer. According to Armstrong, many institutions have already adopted this practice.

Armstrong believes that some clinicians might be deterred by cost and lack of familiarity with IP. "We haven't done a cost analysis, but we expect IP therapy to be more expensive than intravenous [due to] more drug and more staff time," she said.

Patients with adhesions, surgical complications or poor kidney function, and those who have had the left side of their colon removed during surgery, are not ideal candidates for IP therapy.

It also is not clear whether the procedure has any benefit for recurrent disease or for patients with large amounts of residual disease after surgery.

Robert Bristow, director of the Johns Hopkins Ovarian Cancer Center, said, "The first and most important step is good surgery. If you don't start with a surgeon specializing in gynecologic oncology who can effectively remove most of the tumor, then intraperitoneal chemotherapy may not work."

According to Armstrong, fewer than 50 percent of U.S. women with ovarian cancer seek a gynecologic oncology specialist for their surgery, despite research showing better outcomes for this group.

IP chemotherapy was first studied half a century ago for colon cancer but never gained popularity for ovarian cancer despite several studies that hinted at survival benefits. The benefits were overshadowed by the promise of new chemotherapy drugs such as paclitaxel, one of the chemo drugs used in Armstrong's study.

The second chemotherapy agent used in the current study was cisplatin, a drug that most clinicians bypass in favor of carboplatin, a faster and better-tolerated drug. But since it does not appear to penetrate tumors as well, most believe that carboplatin is not currently a drug of choice for IP therapy.

"Modern dosing techniques may reveal that may not be true, and we're conducting an early study of IP therapy with carboplatin," Armstrong said. Some investigators are also studying ways to add new agents that are highly specific for cancer cells into the IP regimen.

In addition to Armstrong, authors are Brian Bundy, of the Gynecologic Oncology Group and Roswell Park Cancer Institute; Lari Wenzel, University of California at Irvine; Helen Q. Huang, Gynecologic Oncology Group; Rebecca Baergen, New York Presbyterian Hospital; Shashikant Lele, Roswell Park Cancer Institute; Larry J. Copeland, Ohio State University; Joan L. Walker, University of Oklahoma; and Robert A. Burger, University of California, Irvine.


Related Web sites

Johns Hopkins Ovarian Cancer Center
Johns Hopkins Kimmel Cancer Center


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