Cytotoxic Drugs in Treatment of Nonmalignant Diseases

Abstract

The basis for using cytotoxic drugs in inflammatory diseases of uncertain cause is their immunosuppressive properties. These drugs interrupt nucleic acid and protein synthesis, thereby inhibiting various immune responses at different stages. Specific inhibition of an immune response is possible through drug-induced tolerance. Many of the agents have anti-inflammatory properties that may be a major factor in their efficacy. In short-term controlled trials, both cyclophosphamide and azathioprine have been useful in treatment of rheumatoid arthritis and systemic lupus erythematosus, cyclophosphamide in nephrosis, and methotrexate and azathioprine in psoriasis and psoriatic arthritis. Azathioprine was ineffective in iridocyclitis, nephritis, nephrosis, Crohn's disease, chronic hepatitis, and asthma. Cytotoxic drugs may increase the risk of infection, predispose to malignancy, and increase mutations in offspring. Specific side effects include hemorrhagic cystitis from cyclophosphamide, cirrhosis from methotrexate, and altered germ cell production by alkylating agents. Only long-term controlled trials, not uncontrolled reports or positive short-term controlled trials, will justify widespread clinical use of these drugs in inflammatory diseases.