Key Terms: Deoxycytidine, Metastasis, Platelet, Pyrimidine.
Definition
Gemcitabine is a drug that is used to treat advanced stages of pancreatic, lung, and other cancers. Its brand name is Gemzar.
Purpose
Gemcitabine is used to treat pancreatic cancer, particularly when it has metastasized, or spread to other parts of the body (Stage IVB). In combination with the drug cisplatin, gemcitabine is the first-line treatment for inoperable, metastasized non-small cell lung cancer. Sometimes it is used to treat cancers of the bladder or breast, or epithelial ovarian cancer.
Description
Gemcitabine is a relatively new anticancer drug. It is a type of medicine called a pyrimidine antimetabolite because it interferes with the metabolism and growth of cells. It does this by replacing the pyrimidine deoxycytidine in DNA, thereby preventing the DNA from being manufactured or repaired. As a result, cells cannot reproduce and eventually die.
Gemcitabine was approved by the U.S. Food and Drug Administration (FDA) to treat pancreatic cancer in 1998 and non-small cell lung cancer in 2002. Gemzar may relieve pain and other symptoms of advanced pancreatic cancer and increase survival time by several weeks to two months. Clinical studies of pancreatic cancer are comparing the effectiveness of combination treatments using gemcitabine with fluorouracil (5-FU), cisplatin, streptozocin, or radiation therapy. Gemcitabine has activity against metastatic bladder cancer and recurrent ovarian cancer, and further clinical trials are underway. Gemcitabine is being evaluated for its effectiveness in the treatment of uterine, stomach, laryngeal and hypopharyngeal, and colon and rectal cancers.
Recommended Dosage
Gemcitabine is administered by injection over a period of 30 minutes. The dosage and number of administrations depend on a variety of factors, including the type of cancer, body size, the patient's sex, and other concurrent treatments.
Precautions
Gemcitabine may temporarily reduce the number of white blood cells, particularly during the first 10–14 days after administration. A low white blood cell count reduces the body's ability to fight infection. Thus, it is very important to avoid exposure to infections and to receive prompt medical treatment. Immunizations (vaccinations) should be avoided during or after treatment with gemcitabine. It also is important to avoid contact with individuals who have recently taken an oral polio vaccine. Treatment with gemcitabine may cause chicken pox or shingles (herpes zoster) to become very severe and spread to other parts of the body.
Gemcitabine also may lower the blood platelet count. Platelets are necessary for normal blood clotting. The risk of bleeding may be reduced by using caution when cleaning teeth, avoiding dental work, and avoiding cuts, bruises, or other injuries.
Gemcitabine can cause birth defects and fetal death in animals. Therefore, this drug should not be taken by pregnant women or by either the man or woman at the time of conception. Women usually are advised against breast-feeding while taking this drug.
Side Effects
Gemcitabine affects normal cells as well as cancer cells, resulting in various side effects. The most common side effects are related to reduction in red and white blood cells and blood platelets. These side effects may include symptoms of infection or unusual bleeding or bruising. Older patients are more likely to suffer from low blood cell counts after treatment.
Flu-like symptoms are common following the first treatment with gemcitabine. Other common side effects of gemcitabine may include:
- nausea
- vomiting
- chills and fever
- constipation
- diarrhea
- loss of appetite (anorexia)
- headache
- muscle pain
- weakness or fatigue
- shortness of breath
- blood in urine or stools
- skin rash
- swelling of the hands, feet, legs, or face
- insomnia
Less common side effects of gemcitabine may include:
- cough or hoarseness
- lower back or side pain
- painful or difficult urination
- chest, arm, or back pain
- difficulty with speech
- fast or irregular heartbeat
- high blood pressure
- pain or redness at the site of injection
- numbness or tingling in hands or feet
- sores or white spots on lips and in mouth
- hair loss (alopecia)
- itching
Some of these side effects may occur or continue after treatment with gemcitabine has ended. Itching, hives, swelling, or a skin rash, particularly if accompanied by breathing problems, may indicate an allergic reaction to gemcitabine. Some researchers have coined the term gemcitabine-induced severe pulmonary toxicity, or GISPT, to describe an inflammatory reaction in the lungs following treatment with gemcitabine. The incidence of GISPT is estimated to range between 0.5% and 5% of patients receiving the drug.
Additional side effects of gemcitabine may be symptoms associated with liver or kidney malfunction. Furthermore, kidney or liver disease may cause gemcitabine to be removed from the body at a slower rate, thus increasing the effects of the drug.
Another potentially fatal side effect of gemcitabine is vasculitis, or inflammation of blood or lymph vessels. A group of physicians in Iowa reported on two cases of women who died of necrotizing enterocolitis resulting from vasculitis associated with gemcitabine treatment for ovarian cancer. A case of vasculitis in a male patient treated with gemcitabine for bladder cancer was reported in Turkey.
Interactions
Previous treatment with radiation or other anti-cancer drugs can increase the risk of very low blood counts with gemcitabine. Serious problems may develop in areas previously treated with radiation.
Drugs that may interact with gemcitabine, or that may increase the risk of infections while being treated with gemcitabine, include live vaccines and warfarin. Because some other medications have a tendency to interact with gemcitabine, patients should alert their doctor to any drugs they are taking.
It is also important not to take any medicines containing aspirin during treatment with gemcitabine, since aspirin can increase the chances of excessive bleeding.
Resources
Books
Beers, Mark H., MD, and Robert Berkow, MD, editors. "Pancreatic Tumors." Section 3, Chapter 34 In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2002.
Karch, A. M. Lippincott's Nursing Drug Guide. Springhouse, PA: Lippincott Williams & Wilkins, 2003.
Periodicals
Barlesi, F., P. Villani, C. Doddoli, et al. "Gemcitabine-Induced Severe Pulmonary Toxicity." Fundamental and Clinical Pharmacology 18 (February 2004): 85–91.
Birlik, M., S. Akar, E. Tuzel, et al. "Gemcitabine-Induced Vasculitis in Advanced Transitional Cell Carcinoma of the Bladder." Journal of Cancer Research and Clinical Oncology 130 (February 2004): 122–125.
Geisler, J. P., D. F. Schraith, K. J. Manahan, and J. I. Sorosky. "Gemcitabine Associated Vasculitis Leading to Necrotizing Enterocolitis and Death in Women Undergoing Primary Treatment for Epithelial Ovarian/Peritoneal Cancer." Gynecologic Oncology 92 (February 2004): 705–707.
Li, D., K. Xie, R. Wolff, and J. L. Abbruzzese. "Pancreatic Cancer." Lancet 363 (March 27, 2004): 1049–1057.
Organizations
American Society of Health-System Pharmacists (ASHP). 7272 Wisconsin Avenue, Bethesda, MD 20814. (301) 657-3000.
United States Food and Drug Administration (FDA). 5600 Fishers Lane, Rockville, MD 20857-0001. (888) INFO-FDA.
—Margaret Alic, Ph.D.; Rebecca J. Frey, PhD
