Cyclophosphamide

Cyclophosphamide is a drug from the drug class of cytostatics. It is used for the treatment of cancer and for the therapy of severe autoimmune diseases.

What is Cyclophosphamide?

Cyclophosphamide is a drug with an alkylating effect. Alkylating agents are chemical substances that can introduce alkyl groups into DNA. Cyclophosphamide belongs to the group of mustard gas-nitrogen compounds and thus to the cytostatics. Cytostatics are drugs that inhibit cell growth and / or cell division. They are used in particular to treat cancer as part of chemotherapy.

In search of a cancer drug, chemists at the pharmaceutical company Asta Medica produced a derivative of the phosphamide mustard. Based on this, cyclophosphamide was discovered in 1956. The drug was finally patented in 1962. Today cyclophosphamide is made from bisamine and phosphorus oxychloride. This creates phosphoric acid amide dichloride. In the reaction with 3-amino-1-propanol, in the presence of the basic solvent triethylamine, the substance mixture cyclophosphamide is formed.

Pharmacological effect

Cyclophosphamide is one of the prodrugs. Prodrugs are inactive precursors of drugs that only develop their effect through various metabolic processes in the body. The cytotoxic effect of the cyclophosphamide is only activated in the liver. Thus, cyclophosphamide per se is a substance that initially has no cytostatic effect.

The bioavailability after oral administration is over 75 percent. The half-life is between three and twelve hours. In the cells of the liver, the drug is hydroxylated by the cytochrome P450 system. This produces 4-hydroxycyclophosphamide-aldophosphamide. This splits off acrolein and thus becomes phosphoramide mustard. Phosphoramidmustard is an alkylane with an active bifunction. It damages the DNA of the cells by so-called cross links. Cross links are cross-links between the individual DNA strands. Due to the DNA damage, the cells can no longer divide. The proliferation of the cells is thus inhibited.

Medical application & use

Cyclophosphamide is used as a cytostatic agent in the treatment of various cancers. As a rule, the drug is combined with other cytostatics in therapy. In adults, cyclophosphamide is used to treat Hodgkin's and non-Hodgkin's lymphoma. Hodgkin and non-Hodgkin lymphomas are malignant diseases of the lymphatic system.

In combination with methotrexate and 5-fluorouracil, cyclophosphamide is administered in the so-called CMF scheme in the treatment of breast cancer (breast cancer). Other indications for cyclophosphamide are soft tissue sarcoma and Ewing sarcoma. Ewing's sarcoma is the second most common type of bone cancer in children.

Cyclophosphamide is also used to mobilize stem cells for stem cell apheresis and as a conditioning treatment before immunotherapy and stem cell transplants. In children, not only Ewing's sarcoma is treated with cyclophosphamide. Other areas of application of the drug are medulloblastoma, neuroblastoma, retinoblastoma and severe aplastic anemia.

Cyclophosphamide is not only used in cancer therapy. Even severe courses of autoimmune diseases such as granulomatosis, rheumatoid arthritis or systemic lupus erythematosus (SLE) are treated with cyclophosphamide. Several studies have also shown an improvement in symptoms in multiple sclerosis. However, there is currently no approval for the treatment of multiple sclerosis.

Risks & side effects

Cyclophosphamide should not be used during pregnancy. Adequate contraception must be used during therapy so that pregnancy cannot occur under any circumstances. In addition, vaccinations with live vaccines must not be carried out during treatment with cyclophosphamide. The immunosuppressive effect of the drug could otherwise lead to potentially life-threatening infections.

As part of therapy with cyclophosphamide, there may be a reduction in white blood cells (leukocytes). Common side effects include nausea and hair loss. Cumulative doses of cyclophosphamide increase the risk of leukemia and bladder tumors. As part of chemotherapy with the drug, hemorrhagic inflammation of the bladder (cystitis) can occur. Therefore, the drug mercapto ethanesulfonate sodium (Mesna) is administered in parallel with the cyclophosphamide. Whether this gift is really helpful is currently still controversial. Administration of Mesna is usually not necessary, particularly with lower doses of cyclophosphamide, for example in the treatment of autoimmune diseases.

Administration of cyclophosphamide can lead to infertility in both men and women. Cryopreservation of egg cells and sperm is therefore recommended prior to treatment for patients who wish to have children.