Azathioprine (Cancer treatment)
Azathioprine is a medication primarily used to prevent organ rejection in transplant patients and to treat autoimmune diseases, where the immune system attacks the body's own tissues. Despite its effectiveness, long-term use of azathioprine has been associated with an increased risk of certain cancers, including non-Hodgkin lymphoma, skin cancers, and liver cancers. The drug works by inhibiting DNA synthesis, which suppresses the immune system, leading to potential side effects such as leukopenia (decreased white blood cells), thrombocytopenia (decreased platelets), and increased susceptibility to infections and bleeding.
Originally introduced in the 1970s as an antirejection drug, azathioprine was crucial in the early days of organ transplantation. While it has proven effective, studies indicate that both transplant patients and those with autoimmune diseases treated with azathioprine exhibit higher incidences of malignancies. Consequently, alternatives like mycophenolate mofetil are increasingly being favored for their lower carcinogenic risks. Nonetheless, azathioprine continues to play a significant role in clinical practice, necessitating careful monitoring of patients who are prescribed this medication.
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Azathioprine (Cancer treatment)
ROC STATUS: Known human carcinogen since 1985
ALSO KNOWN AS: Azasan, Imuran
RELATED CANCERS: Non-Hodgkin lymphoma, cancers of the skin and liver
DEFINITION: Azathioprine is a drug prescribed for transplant patients and those whose immune systems attack their own tissues, but long-term usage causes cancer.
Exposure routes: Ingestion, intravenous injection, and inhalation
Where found: The drug is found in hospitals, used for transplant and autoimmune disease patients, and in manufacturing plants that make and package the drug.
At risk: Patients who take azathioprine and workers who manufacture it.
Etiology and symptoms of associated cancers: In the liver, azathioprine is converted to 6-mercaptopurine, which inhibits deoxyribonucleic acid (DNA) synthesis. This suppresses the immune system and can also cause a dangerous decrease in white blood cells (leukopenia) and platelets (thrombocytopenia), increased risk of infection and bleeding, gastrointestinal disturbances, and liver damage. The substance 6-mercaptopurine also inserts between adjacent nucleotide bases in DNA molecules and causes mutations that lead to various types of cancer.
Azathioprine increases the risk of developing squamous cell carcinoma, a type of skin cancer that appears as persistent wartlike growths, scaly patches, or open sores that crust over and bleed; non-Hodgkin lymphoma, a blood-based cancer of white blood cells called T cells, the most common symptoms of which are painless swelling of the neck or underarm lymph nodes, unexplained fever, loss of weight and appetite, itchy skin with reddened patches, and constant fatigue; and cancer of the bile ducts or hepatobiliary carcinomas, whose symptoms include jaundice, itching, stomach pain, weight loss, and fever.
History: The pioneer of liver transplantation, Sir Roy Yorke Calne, first used azathioprine to prevent organ rejection in liver transplant patients. Azathioprine was the standard antirejection drug in the 1970s for organ transplants, and it was later enlisted to treat patients who suffer from diseases that result when the immune system attacks the patient’s own body (autoimmune diseases).
Several epidemiological studies have shown that transplant patients who took azathioprine were at a high risk for different types of tumors. Other patients who took azathioprine but were not transplant patients, including those with rheumatoid arthritis, systemic lupus, inflammatory bowel disease, and certain skin and renal diseases, have also shown higher incidences of such malignancies, but not as high as those observed in transplant patients, since the dosages to treat autoimmune diseases are lower than those used for transplant patients. Mycophenolate mofetil, which is not as carcinogenic, is gradually replacing azathioprine as the antirejection drug of choice. Still, in the twenty-first century, azathioprine remained an important and still-used medication for transplant patients and patients with autoimmune diseases. If a patient’s health dictates, doctors may choose a different medication. However, although patients on azathioprine need increased surveillance, it remained a utilized medication.
Bibliography
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