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Cyclophosphamide: Mechanism of Action, Indications and Side Effects

Dec 2，2022

Cyclophosphamide is a nitrogen mustard used to treat lymphomas, myelomas, leukemia, mycosis fungoides, neuroblastoma, ovarian adenocarcinoma, retinoblastoma, and breast carcinoma.

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Mechanism of Action

The majority of the antineoplastic effects of cyclophosphamide are due to the phosphoramide mustard formed from the metabolism of the drug by liver enzymes like cytochrome P-450. Hepatic enzymes first convert cyclophosphamide to hydroxycyclophosphamide and then subsequently metabolized to aldophosphamide. Aldophosphamide is cleaved to the active alkylating agent phosphoramide mustard and acrolein. The phosphoramide metabolite forms cross-linkages within and between adjacent DNA strands at the guanine N-7 position. These modifications are permanent and eventually lead to programmed cell death.

Indications

According to the FDA, cyclophosphamide is mainly indicated for use in the treatment of malignant lymphomas stages III and IV, as designated by the Ann Arbor staging system. These may include Hodgkin and Non-Hodgkin lymphoma, lymphocytic lymphoma, small lymphocytic lymphoma, Burkitt lymphoma, and multiple myeloma.

Other FDA approved indications of cyclophosphamide include use in the treatment of breast cancer, disseminated neuroblastomas, retinoblastoma, minimal change nephrotic syndrome in pediatric patients, and ovarian adenocarcinomas. As an effective immunosuppressive agent, cyclophosphamide multiple studies have found cyclophosphamide useful in the treatment of autoimmune diseases such as multiple sclerosis. Cyclophosphamide has also been prescribed pretransplant as an immunosuppressant to prevent transplant rejection and graft-vs-host complications.

Side Effects

Cyclophosphamide often causes nausea, vomiting, and loss of appetite. However, it is very important that you continue to use the medicine even if you begin to feel ill. Do not stop taking this medicine without first checking with your doctor. Ask your doctor for ways to lessen these effects.