Cyclophosphamide
Cyclophosphamide is a potent anticancer drug classified as an alkylating agent and is derived from nitrogen mustard. It is primarily used in the treatment of various cancers, including those of the ovaries, breast, blood, lymph, and nervous system, as well as for autoimmune disorders such as rheumatoid arthritis. Available in oral tablets or as an intravenous injection, cyclophosphamide can have significant side effects, including inflammation of the bladder, nausea, hair loss, and bone marrow suppression. Notably, while it is effective in treating certain cancers, it is also associated with the risk of developing secondary cancers, particularly bladder cancer and hematologic malignancies like leukemia, as long-term side effects. Patients, especially those who have experienced complications like hemorrhagic cystitis during treatment, are at higher risk for these secondary conditions. First synthesized in 1958, cyclophosphamide has been widely used since the 1960s; however, it is important for healthcare professionals and patients to be aware of its potential risks, particularly for those handling the drug or undergoing treatment. As of the 2020s, cyclophosphamide is no longer produced in the US, although it remains a crucial part of cancer therapy in various parts of the world.
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Cyclophosphamide
ROC STATUS: Known human carcinogen since 1980
ALSO KNOWN AS: Cytoxan, Cytoxan Lyophilized, Neosar
RELATED CANCERS: Bladder cancer, myeloproliferative and lymphoproliferative malignancies (leukemias)
DEFINITION: Cyclophosphamide is a highly toxic anticancer drug that belongs to a family of drugs known as alkylating agents. It is a derivative of nitrogen mustard.
Exposure routes: Orally in twenty-five or fifty milligram tablets or by intravenous injection as part of medical treatment. Skin contact or dust inhalation is possible during the manufacturing process or while handling the drug during preparation and administration.
Where found: Cyclophosphamide is used in the treatment of various cancers of the ovaries, breast, blood, lymph, and nervous system including lymphoma, leukemia, retinoblastoma, multiple myeloma, and mycosis fungoides; in bone marrow transplant as part of a peripheral stem-cell mobilization or preparative regimen; as an immune-suppressive agent following bone marrow or solid organ transplant; and to treat autoimmune disorders such as rheumatoid arthritis.
At risk: People who have been previously treated with cyclophosphamide alone or in association with other chemotherapy drugs; health professionals (nurses, pharmacists, physicians) who handle the drug during preparation, administration, and cleanup; and workers involved in the manufacturing process. The general population is not considered to be at risk.
Etiology and symptoms of associated cancers: Cyclophosphamide is used to treat cancer, but studies show that it can cause a secondary cancer as a long-term side effect. It is a cytotoxic drug that affects the growth of cancer cells by interfering with the deoxyribonucleic acid (DNA) within the cells. Normal, noncancerous cells are affected as well, causing side effects that may include inflammation and bleeding from the bladder (hemorrhagic cystitis), bone marrow suppression, nausea and vomiting, and hair loss (alopecia). It is the damage to cellular DNA that can lead to a secondary cancer months or years after treatment with cyclophosphamide. Patients who experience hemorrhagic cystitis during treatment with cyclophosphamide have been shown to be at a higher risk of bladder cancer after treatment. Signs and symptoms of bladder cancer include blood in the urine (hematuria), pelvic pain, pain during urination, and a frequent urge to urinate. Patients who are treated with cyclophosphamide for primary myeloproliferative or lymphoproliferative malignancies are at a higher risk for a secondary hematologic malignancy (leukemia) as a long-term side effect of treatment. The symptoms of secondary acute leukemia include recurrent infections, bone and joint pain, swollen lymph nodes, and shortness of breath.
History: Cyclophosphamide was first synthesized in 1958, and the first clinical trials were published at the end of the 1950s. It has been in widespread use as a chemotherapeutic agent since the 1960s. In the late 2000s, eleven US pharmaceutical companies produced drugs containing cyclophosphamide, and seven US suppliers offered the drug. By the 2020s, cyclophosphamide was no longer produced in the US.
Bibliography
"Cyclophosphamide." Report on Carcinogens 15th ed. National Toxicology Program, Dept. of Health and Human Services, 2021, www.ncbi.nlm.nih.gov/books/NBK590840. Accessed 20 June 2024.
"Cyclophosphamide (Oral Route, Intravenous Route)." Mayo Clinic, 1 May 2024, www.mayoclinic.org/drugs-supplements/cyclophosphamide-oral-route-intravenous-route/description/drg-20063307. Accessed 20 June 2024.
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Rimando, Joseph, et al. "How I Prevent GVHD in High-Risk Patients: Posttransplant Cyclophosphamide and Beyond." Blood, vol. 141, no. 1, 2023, pp. 49-59. doi.org/10.1182/blood.2021015129.
Walker, Cucnhat, and Sidhartha Ray. "Drugs That Act on the Immune System: Immunosuppressive and Immunostimulatory Drugs." Side Effects of Drugs Annual, vol. 41, 2019, pp. 435-459. doi.org/10.1016/bs.seda.2019.07.008.