Ovarian Cancer

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Radiation

Radiotherapy, otherwise known as radiation therapy, is not a common treatment for ovarian cancer in the United States. This is because many American women are diagnosed with late-stage cancers that have spread widely within the abdominal cavity (see also Signs and Symptoms of Ovarian Cancer). To be effective, radiotherapy must include all cancer cells within the radiation field, and abdominal organs like the liver, kidneys, and small bowel may not be able to withstand the doses of radiation required to destroy all tumorous tissue. Yet if the ovarian cancer is confined to one or both ovaries without spread to abdominal organs or pelvic lymph nodes, radiotherapy may be an option.

Radiotherapy may be used to kill cancer cells from a cyst that ruptures during surgical removal of an ovary, or it may be used to treat certain patients who appear cancer-free or who have only microscopic evidence of disease at second-look surgery. It is historically the treatment of choice for germ cell tumors known as dysgerminomas. However, recently it has been found that chemotherapy can cure a percentage of such patients.

Radiotherapy uses high-energy, ionizing radiation (e.g., gamma rays) to kill cancer cells. Radiotherapy can be delivered in two ways: (1) by a radiotherapy device, which is used outside of the body in a manner similar to that of an x-ray machine, and (2) by injection of a short-lived radioactive chemical (e.g., radioactive phosphorus) into the peritoneal cavity.

Because cancer cells usually multiply faster than most bodily tissues, they are especially affected by radiation, which prevents cell division and the formation of DNA (human genetic material). Yet the bodily tissues that also divide rapidly—such as the lining of the digestive tract, hair, and skin—are particularly vulnerable to radiotherapy. The specific side effects of abdominal (injected) radiotherapy include: abdominal pain, nausea, diarrhea, inflammation of the peritoneum (tissue that lines the abdominal cavity), formation of abdominal adhesions (fibrous bands), obstruction of the small bowel, and lowered blood counts. If radiotherapy is applied externally by a radiotherapy device, side effects may include skin irritation, edema (swelling), and skin darkening at the treatment site.

Other Forms of Therapy

Besides the ovarian cancer therapies that are currently in use—surgery, chemotherapy, radiotherapy—a number of treatment strategies are in development. Hundreds of clinical trials have been performed to evaluate the benefits, safety, and side effects of new techniques such as gene therapy and hormone therapy. But, although some early findings look promising, final results on the effectiveness of these new therapies will not be available for a number of years.

Gene Therapy
Gene therapy eventually may provide some control over cancer susceptibility and its treatment. Ovarian cancer, like all cancers, is believed to result from a build-up of genetic defects within the cells. Genetic defects may be inherited, or they may be caused by exposures to environmental or other factors that damage the genes (see also What Causes Ovarian Cancer). Genetic engineers hope to correct such damage by transplanting copies of normal genes into cells with genetic defects. In addition, genetic manipulation may enable researchers to alter tumor cells so that they "commit suicide," are targeted by the immune system, or become more sensitive to chemotherapy. Investigators also have spent a lot of time trying to improve the resistance of bone marrow cells to chemotherapeutic agents, so that the doses of such drugs can be intensified.

The practical applications of gene therapy are still being refined. Yet, as more is learned about the genetic makeup of ovarian cancer and its biochemical pathways, the closer researchers come to developing workable methods of genetic therapy.

Hormone Therapy
Over the past few decades, there have been many reports of the potential benefits of hormone treatments in patients with ovarian cancer that does not respond to conventional therapy. For example, individuals with treatment-resistant (refractory) epithelial cancers have been treated with:

• progestins - crude forms of the female sex hormone progesterone; e.g., oral Provera® (medroxyprogesterone acetate, MPA), intramuscular Depo-Provera® (medroxyprogesterone acetate suspension), Megace® (megestrol acetate);
• estrogens - for example, diethylstilbestrol (DES);
• combination estrogen/progestin therapy;
• antiestrogens - for example, Nolvadex® (tamoxifen);
• androgens - male sex hormones for example, Halotestin® (fluoxymesterone); and
• gonadotropin-releasing hormone (GnRH) - a hormone of the hypothalamus that stimulates the release of ovary-related hormones from the pituitary gland.

Unfortunately, the responses to such therapies have been variable and not particularly effective in the management of this disease. Nevertheless, some researchers believe that hormone therapy with progestins eventually may play a role in the management of patients with sex cord-stromal tumors.

Experts guess that the patients most likely to respond to antiestrogen therapy (tamoxifen) are those who are estrogen receptor positive—that is, individuals who have receptors (molecules on/within a cell that recognize and bind with certain substances) for the female sex hormone estrogen (ER positive). Estrogen receptor-positive tumors may be biologically less malignant than receptor-negative tumors.

In addition, recent findings suggest that hormone replacement therapy (HRT) is not harmful to women who have been treated for epithelial ovarian cancer. But HRT therapy is controversial, since some physicians believe that the use of estrogen might increase the likelihood of cancer recurrence, for example in women with well-differentiated endometrioid carcinomas that may be hormone-sensitive.

As yet, there is no conclusive evidence that estrogen use in such patients is risky –or that it is safe.

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