Melphalan
Melphalan is a potent anticancer drug classified as an alkylating agent and is a derivative of nitrogen mustard. Commonly used to treat various cancers, including ovarian cancer, multiple myeloma, and certain leukemias, it can be administered orally or via intravenous injection. Despite its effectiveness in cancer treatment, melphalan is associated with significant risks, including its classification as a known human carcinogen since 1980. This drug can cause secondary cancers, particularly acute leukemia, as a long-term side effect, with the risk increasing with higher cumulative doses.
Health professionals who handle melphalan during preparation and administration, as well as patients receiving the drug, may be at increased risk. Symptoms of secondary acute leukemia include recurrent infections, bone and joint pain, and swollen lymph nodes. The history of melphalan traces back to the development of nitrogen mustards during World War I, which were initially used as chemical weapons. This background highlights the dual nature of such compounds, effective as cancer therapies yet hazardous in terms of potential long-term side effects.
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Melphalan
ROC STATUS: Known human carcinogen since 1980
ALSO KNOWN AS: Alkeran, Evomela, melphalan Injection, melphalan (HEPZATO)
RELATED CANCERS: Acute leukemia
DEFINITION: Melphalan 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 or by intravenous injection as part of medical treatment. Skin contact or dust inhalation is possible during the manufacturing process and in handling of the drug during preparation and administration.
Where found: Used in treating various cancers, including ovarian cancer, Hodgkin’s lymphoma, non-Hodgkin's lymphoma, acute lymphoblastic leukemia, myeloblastic leukemia, neuroblastoma, breast cancer, and multiple myeloma.
At risk: People who have been previously treated with melphalan alone or in association with other chemotherapy drugs; health professionals (nurses, pharmacists, physicians) who handle the drug during preparation, administration, and cleanup; workers involved in the manufacturing process. The general population is not considered to be at risk.
ETIOLOGY AND SYMPTOMS OF ASSOCIATED CANCERS: Melphalan is used to treat cancer but can itself cause 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. It is the damage to cellular DNA that can lead to secondary cancer months or years after treatment with melphalan. Studies of melphalan (and other alkylating agents) indicate that the risk of secondary leukemia increases with the cumulative dose and chronicity of treatment. In one study, the ten-year cumulative risk of developing acute leukemia or myeloproliferative syndrome after melphalan therapy was 19.5 percent for cumulative doses ranging from 730 to 9,652 milligrams (mg). In this study and an additional study, the ten-year cumulative risk of developing acute leukemia or myeloproliferative syndrome after melphalan therapy was less than 2 percent for cumulative doses under 600 mg. However, there is no known cumulative dose below which there is no risk of developing a secondary malignancy. The symptoms of secondary acute leukemia include recurrent infections, bone and joint pain, swollen lymph nodes, and shortness of breath.
History: Nitrogen mustards were developed as a derivative of sulfur mustard gas and were first used as a weapon of war in 1917. Observation of military personnel exposed to sulfur mustard showed that it lowered the white blood cell count. Drugs derived from nitrogen mustard, such as melphalan, were introduced into the clinical setting in 1946.
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