Ovarian cancer: Gaining a new lease on life

June 19, 2006

Delivering chemo agents intraperitoneally is extending survival

Although the incidence of ovarian cancer has been slowly declining, it still has the highest mortality rate of all the female reproductive malignancies. Recent statistics show that only 45% of women survive five years after an ovarian cancer diagnosis. Conceivably, this rate could increase if the cancer is detected early, but, unfortunately, women with ovarian cancer have few, if any, symptoms until the disease is advanced.

The National Cancer Institute (NCI) issued a clinical announcement in January stating that the intraperitoneal (IP) route of administration is now the preferred way to deliver chemotherapy to women with stage III ovarian cancer who have undergone surgical cytoreduction to debulk the tumor. NCI issues such announcements only when a clinical trial identifies an intervention that substantially improves the outcome for a significant number of people, and when that intervention is available to the general public outside of a trial setting.

Patients with ovarian cancer often have metastases at other sites, including intestines, kidneys, and lymph nodes. The IP route, in contrast to intravenous (IV) administration of chemotherapy, can deliver high concentrations of drugs directly to sites where their actions are most needed. Estimates suggest that the IP pharmacologic advantage, in terms of intraperitoneal-to-plasma concentration ratios, for platinum compounds and taxanes is more than 20 and 1,000, respectively.

With IP drug delivery, the drugs have longer half-lives in the peritoneal cavity than when administered IV. Additionally, cisplatin (but not paclitaxel) slowly leaves the peritoneal cavity and enters the bloodstream, which can deliver chemotherapy to hidden sites of disease.

IP delivery is made possible by a surgically implanted catheter. Drugs are infused into the abdominal cavity, and patients are encouraged to change positions at 15-minute intervals for two hours to ensure adequate drug distribution. There is no need to drain the infused fluid; it is absorbed by the body over the course of a few days. However, bloating, increased abdominal pressure, decreased appetite, and fast frequent breathing often accompany IP drug delivery.

Favorable trial results

During the past decade, two large randomized studies reported improved outcomes in women with optimally debulked stage III ovarian cancer when treated via IP chemotherapy. In one of these studies, the progression-free survival was 28 months for those on IP treatment versus 22 months for those receiving conventional chemo-a gain that was deemed to be statistically significant. In the other study, median overall survival increased by eight months for those receiving IP treatments and the risk of death was also lower.

Despite these reports published in 1996 and 2001, IP chemotherapy has not been adopted as standard care in the United Stated for several reasons. IP therapy is often viewed as an outdated method. It requires surgical expertise for both effective tumor debulking and catheter placement. Also, administration of IP chemotherapy is more complex, more time-consuming, and is associated with a greater risk of toxicity than IV therapy.

However, the Gynecologic Oncology Group once again demonstrated significant improvements in progression-free survival and overall survival using an IP regimen to treat women with ovarian cancer (New England Journal of Medicine, 2006; 354:34), and the benefits of this approach cannot be ignored any longer.