Ovarian Cancer - Putting Chemotherapy in its Proper Place

In the United States, cancer of the ovary is diagnosed in 22,000 women annually. While not as common as breast cancer, ovarian cancer has a 1.5% chance of occurring during a woman's lifetime. Unfortunately, at initial detection the disease has progressed beyond the ovaries in 75% of patients - which greatly compromises the ability to cure the disease. In the Rice Hospital Cancer Registry, 18 newly diagnosed cases were recorded over the last five years.

An unusual feature of ovarian cancer is its pattern of spread. While it can metastasize via the lymph system or bloodstream like other cancers, it is much more likely to confine its spread within the abdominal cavity. Oftentimes at the initial surgery there will be dozens or hundreds of nodules scattered about in the peritoneum. The job of the surgeon is to remove the ovaries, tubes, uterus, and as many of these nodules as possible - a procedure known as "debulking." The ability of the chemotherapist to control or cure the disease thereafter depends in part on whether all known sites of cancer have been removed, or at least reduced to less than one centimeter in diameter.

Many years ago, the traditional chemotherapy for ovarian cancer was an oral drug called Melphalan. More recently, intravenous programs including Carboplatin and Taxol have been the standard of care. In either situation, these chemotherapy drugs have depended on the bloodstream to carry them to the malignant cells within the peritoneum.

Decades ago researchers asked the question, "What if we put the chemotherapy drugs into the peritoneal cavity itself?" After all, many years of experience using peritoneal dialysis for treatment of kidney failure had proven that fluid could be introduced safely into the abdomen. So studies were designed to test the safety and effectiveness of such an approach, initially with the drug cis-platinum.

Using this approach, it was found that the concentration of cis-platinum within the abdomen was several-fold higher when the drug was given intraperitoneally compared to intravenously. Furthermore, it was shown that considerable amounts of drug were absorbed from the peritoneum into the systemic circulation. Subsequently the same has been shown for other drugs such as Carboplatin, Taxol, and Etoposide.

In the years that followed, clinical studies by the Gynecology Oncology Group (GOG) and others have shown that use of the peritoneal route for one drug, combined with a second drug given intravenously, produced superior results compared to the same drugs when both are given intravenously. Patients treated via the peritoneal route had superior overall survival and disease-free survival results. This led the National Cancer Institute to issue a clinical advisory suggesting that peritoneal chemotherapy be considered for ovarian cancer patients.

In recent years, increasing numbers of patients from Willmar and the surrounding area have been treated with chemotherapy via the abdominal route. Often at the time of initial surgery a catheter is placed into the peritoneal cavity for future chemotherapy use. Overall this aproach has been quite tolerable and effective, and with very manageable side effects. It is used postoperatively in patients felt to have no known residual disease after their surgery (adjuvant therapy), and in patients who have been "maximally debulked" down to a tumor diameter of one centimeter or less.

On occasion, other cancers arising in the peritoneal cavity are treated in the same manner, with similar results. It is hoped that other novel approaches will be developed to allow oncologists to exploit specific biological behaviors of other cancers, with ovarian cancer being one of the models for such innovation.

William Shimp, M.D.
Medical Oncologist