Melphalan, sold under the brand name Alkeran among others, is a chemotherapy medication used to treat multiple myeloma; malignant lymphoma; lymphoblastic and myeloblastic leukemia; childhood neuroblastoma; ovarian cancer; mammary adenocarcinoma; and uveal melanoma.[ It is taken by mouth or by injection into a vein.][
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Common side effects include nausea and bone marrow suppression.[ Other severe side effects may include anaphylaxis and the development of other cancers.][ Use during pregnancy may result in harm to the fetus.][ It works by interfering with the creation of DNA and RNA.][
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Melphalan was approved for medical use in the United States in 1964.
Medical uses
In the European Union, melphalan is indicated for the treatment of multiple myeloma; malignant lymphoma (Hodgkin, non-Hodgkin lymphoma); acute lymphoblastic and myeloblastic leukemia; childhood neuroblastoma; ovarian cancer; and mammary adenocarcinoma.
In the United States, melphalan is used as a high-dose conditioning treatment prior to hematopoietic progenitor (stem) cell transplantation in people with multiple myeloma.
In August 2023, the US Food and Drug Administration approved melphalan (Hepzato) as a liver-directed treatment for adults with uveal melanoma with unresectable hepatic metastases affecting less than 50% of the liver and no extrahepatic disease, or extrahepatic disease limited to the bone, lymph nodes, subcutaneous tissues, or lung that is amenable to resection or radiation.[ ]
Side effects
Common side effects include:[
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Less common side effects include:
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Severe allergic reactions
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Pulmonary fibrosis (scarring of lung tissue) including fatal outcomes (usually only with prolonged use)
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Alopecia
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Interstitial pneumonitis
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Rash
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Pruritus
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Irreversible bone marrow failure due to melphalan not being withdrawn early enough
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Cardiac arrest
Mechanism of action
Melphalan chemically alters the DNA nucleotide guanine through alkylation, and causes linkages between strands of DNA. This chemical alteration inhibits DNA synthesis and RNA synthesis, functions necessary for cells to survive. These changes cause cytotoxicity in both dividing and non-dividing tumor cells.
Synthesis
4-Nitro-L-phenylalanine ( 1) was converted to its phthalimide by heating with phthalic anhydride, and this was converted to its ethyl ester ( 2). Catalytic hydrogenation produced the corresponding aniline. Heating in acid with oxirane, followed by treatment with phosphorus oxychloride provided the bischloride, and removal of the protecting groups by heating in hydrochloric acid gave melphalan ( 3).
Society and culture
Legal status
On 17 September 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for melphalan.[ Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.] The applicant for this medicinal product is Adienne S.r.l. S.U.[ Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.]
