Metastasis Health Article

Treatment

Surgery

Surgery as a method of cancer treatment has limitations in the therapy of metastatic cancer. It is sometimes used to remove large secondary tumors that are causing pain or interfering with body functions. It also may offer a survival advantage over other therapies, as with limited metastases to the lung or liver.

Chemotherapy

Chemotherapy is frequently used to treat micro-metastases that have entered the patient's bloodstream or lymphatic system. Systemic chemotherapy is the only type of treatment that can act at multiple sites simultaneously. Because of some chemotherapy drugs' side effects and risks (for example, nausea and vomiting, some drugs are implicated in causing some cancers), the likelihood of tumor responsiveness needs to be balanced with the patient's quality of life when selecting chemotherapy.

Radiation

Radiation therapy can be effective in the treatment of metastatic disease, especially for metastases to the brain and bones. It is limited, however, because it treats only a limited area. One complication that is possible with radiation therapy is that it has been associated with an increased rate of secondary cancers in patients who have been previously treated for malignancies. The risk is particularly high in patients who were treated with a combination of radiation and chemotherapy.

Immunotherapy

Immunotherapy, or immunologic therapy, is a modality, or method, of cancer treatment that is still in its experimental stages. It mobilizes the patient's own immune system to fight cancer cells. Immunotherapy is being evaluated in the treatment of metastatic melanoma, renal cell carcinoma, breast tumors, and other tumors. Some of the substances that are being tested in clinical trials are produced by the human body, while others are made in laboratories. The major categories of substances used in immunotherapy include:

• Interferons. Interferons are proteins produced by virus-infected cells that limit further reproduction of the virus and stimulate resistance to the infection.
• Interleukins. Interleukins are small proteins that promote the growth and activation of the body's white cells. Interleukin-2, known as IL-2 or aldesleukin, is approved for the treatment of metastatic melanoma and renal cell carcinoma.
• Tumor necrosis factor (TNF). TNF is a protein that was discovered in 1975. It destroys cells that show unusually rapid growth and stimulates the production of inter-leukins.

• Monoclonal antibodies. Monoclonal antibodies are antibodies produced in laboratory-grown cell clones in order to achieve greater abundance and uniformity than are found in antibodies produced in the body.
• Vaccines. Cancer vaccines are intended to stimulate the body's killer T-cells (a specialized type of white blood cell) to attack tumor cells. Some vaccines being tested are made from relatively rare white blood cells called dendritic cells; others are made from genetically altered tumor cells.

Newer therapies for metastatic cancer

Recent advances in understanding the process of metastasis have led to some new approaches to treatment.

GENE THERAPY.

Some researchers are investigating ways to replace a mutated p53 tumor suppressor gene, or to inhibit an activated ras oncogene. Another approach involves the use of angiogenesis inhibitors to suppress metastatic tumors. An antibody to VEGF, called anti-VEGF, is presently being used in clinical trials for patients with late-stage colon, breast, and lung cancers. A second angiogenesis inhibitor that is being tested is endostatin.

Other researchers are studying substances that trigger apoptosis in defective cells or prevent the uncontrolled multiplication of tumor cells.

ISOLATED PERFUSION.

Isolated perfusion is the treatment of metastatic melanoma and sarcoma to the extremities by isolating the vasculature (blood vessels) of the affected extremity, and then delivering high doses of chemotherapeutic drugs directly to the area of metastatic disease. The limb is then flushed before re-establishing circulation. With this technique, it becomes possible to deliver doses of drugs regionally that would otherwise be very toxic or lethal if delivered systemically.

HYPERTHERMIA.

Hyperthermia is the use of therapeutic heat to treat cancers on and inside the body. The goal of hyperthermia is to shrink and destroy cancer without harming noncancerous cells. The treatment can be delivered directly to the tumor, to an area of the body, or to the whole body. Research has established that the effectiveness of some forms of radiation therapy and chemotherapy are enhanced when combined with hyperthermia. In 2001, the American Cancer Society acknowledges that hyperthermia can make the cancer cells of some cancers more responsive to treatment, but still considers the treatment experimental, especially in whole-body form. The National Institutes of Health are sponsoring ongoing clinical trials studying hyperthermia. Patients with extensive metastasis may not be good candidates for hyperthermia.

Alternative and complementary therapies for metastatic cancer

The National Center for Complementary and Alternative Medicine (NCCAM) is sponsoring new as well as ongoing trials of alternative treatments for metastatic cancer. One ongoing trial involves PC-SPES, a combination of eight Chinese herbs that is used to treat prostate cancer. Other trials are evaluating the use of herbal remedies to treat the side effects of chemotherapy. The National Cancer Institute (NCI) makes information about ongoing clinical trials available. Patients can contact the NCI or the NCCAM at the numbers and web sites listed below.

See Also Cancer biology; Cancer genetics; Hepatic arterial infusion; Carcinogenesis

Resources

BOOKS

Aminoff, Michael J., MD, FRCP. "Nervous System." Chapter 24 in Current Medical Diagnosis & Treatment 2001, 40th edition, ed. L. M. Tierney, Jr., MD, et al. New York: Lange Medical Books/McGraw-Hill, 2001.

Chesnutt, Mark S., MD, and Thomas J. Prendergast, MD. "Lung." Chapter 9 in Current Medical Diagnosis & Treat ment 2001, 40th edition, ed. L. M. Tierney, Jr., MD, et al. New York: Lange Medical Books/McGraw-Hill, 2001.

Hall, Stephen S. A Commotion in the Blood: Life, Death, and the Immune System. New York: Henry Holt and Company, 1997. This volume is a history of the development of immunotherapy for general readers.

"Hematology and Oncology." Section 11 in The Merck Manual of Diagnosis and Therapy, edited by Mark H. Beers, MD, and Robert Berkow, MD. Whitehouse Station, NJ: Merck Research Laboratories, 1999.

Lyon, Jeff, and Peter Gorner. Altered Fates: Gene Therapy and the Retooling of Human Life. New York and London: W. W. Norton & Co., Inc., 1996.

Rugo, Hope S., MD. "Cancer." Chapter 4 in Current Medical Diagnosis & Treatment 2001, 40th edition, ed. L. M. Tierney, Jr., MD, et al. New York: Lange Medical Books/McGraw-Hill, 2001.

Shaffrey, Mark E., MD, and Edward R. Laws, MD. "Brain Tumors." In Conn's Current Therapy 2001, ed. Robert E. Rakel, MD, and Edward T. Bope, MD. Philadelphia: W. B. Saunders Company, 2001.

PERIODICALS

Fidler, Isaiah J. "Melanoma Metastasis." Cancer Control Jour nal 2 (5) (2000).

Ruoslahti, Erkki. "How Cancer Spreads." Scientific American, September 1996.

Weinberg, Robert. "How Cancer Arises." Scientific American, September 1996.

ORGANIZATIONS

American Cancer Society (ACS). 1599 Clifton Road, NE, Atlanta, GA 30329. (404) 320-3333 or (800) ACS-2345. Fax: (404) 329-7530. Web site: <http://www.cancer.org>.

National Cancer Institute, Office of Cancer Communications. 31 Center Drive, MSC 2580, Bethesda, MD 20892-2580. (800) 4-CANCER (1-800-422-6237). TTY: (800) 332-8615. Web site: <http://www.nci.nih.gov.>

NIH National Center for Complementary and Alternative Medi cine (NCCAM) Clearinghouse. P. O. Box 8218, Silver Spring, MD 20907-8218. TTY/TDY: (888) 644-6226. Fax: (301) 495-4957. Web site: <http://www.nccam.nih.gov>.

Office of Cancer Complementary & Alternative Medicine of the National Cancer Institute (OCCAM). Email: ncioccam1-r@mail.nih.gov. Web site: <http://www.occam.nci.nih.gov>.

OTHER

National Center for Environmental Research, U.S. Environmental Protection Agency. Web site: <http://www.es.epa.gov/ncerqa>.

Rebecca J. Frey, PhD