Cancer
The main use of cyclophosphamide is with other chemotherapy agents in the treatment of lymphomas, some forms of brain cancer, neuroblastoma, leukemia and some solid tumors.Oncovet C (Chemovet S.A.), is the first-based drug approved in Latin America for veterinary use for canine and feline cancer (carcinomas of anal sacs, bladder carcinomas, urethral carcinomas, hemangiosarcomas, lymphomas, mast cell tumor, osteosarcomas, soft tissue sarcoma), feline cancers (mammary carcinomas, hemangiosarcomas, lymphomas, plasmacytomas, chronic lymphocytic leukemia, acute myelogenous leukemia, mast cell tumor). It can be administered in different treatment schemes, such as induction therapy, adjuvant, neoadjuvant, maintenance and metronomic chemotherapy. Autoimmune diseases
Cyclophosphamide decreases the immune systems response, and although concerns about toxicity restrict its use to patients with severe disease, it remains an important treatment for life-threatening autoimmune diseases where disease-modifying antirheumatic drugs (DMARDs) have been ineffective. For example, systemic lupus erythematosus with severe lupus nephritis may respond to pulsed cyclophosphamide. Cyclophosphamide is also used to treat minimal change disease, severe rheumatoid arthritis, granulomatosis with polyangiitis, Goodpasture syndrome and multiple sclerosis.Because of its potential side effects such as amenorrhea or ovarian failure, cyclophosphamide is used for early phases of treatment and later substituted by other medications, such as mycophenolic acid or ACA. AL amyloidosis
Cyclophosphamide, used in combination with thalidomide or lenalidomide and dexamethasone has documented efficacy as an off-label treatment of AL amyloidosis. It appears to be an alternative to the more traditional treatment with melphalan in people who are ill-suited for autologous stem cell transplant.
Cancer
Cyclophosphamide is carcinogenic and may increase the risk of developing lymphomas, leukemia, skin cancer, transitional cell carcinoma of the bladder or other malignancies. Myeloproliferative neoplasms, including acute leukemia, non-Hodgkin lymphoma and multiple myeloma, occurred in 5 of 119 rheumatoid arthritis patients within the first decade after receiving cyclophosphamide, compared with one case of chronic lymphocytic leukemia in 119 rheumatoid arthritis patients with no history. Secondary acute myeloid leukemia (therapy-related AML, or "t-AML") is thought to occur either by cyclophosphamide-inducing mutations or selecting for a high-risk myeloid clone.This risk may be dependent on dose and other factors, including the condition, other agents or treatment modalities (including radiotherapy), treatment length and intensity. For some regimens, it is rare. For instance, CMF-therapy for breast cancer (where the cumulative dose is typically less than 20 grams of cyclophosphamide) carries an AML risk of less than 1/2000, with some studies finding no increased risk compared to background. Other treatment regimens involving higher doses may carry risks of 1–2% or higher. Cyclophosphamide-induced AML, when it happens, typically presents some years after treatment, with incidence peaking around 3–9 years. After nine years, the risk falls to background. When AML occurs, it is often preceded by a myelodysplastic syndrome phase, before developing into overt acute leukemia. Cyclophosphamide-induced leukemia will often involve complex cytogenetics, which carries a worse prognosis than de novo AML. Pharmacology
Oral cyclophosphamide is rapidly absorbed and then converted by mixed-function oxidase enzymes (cytochrome P450 system) in the liver to active metabolites.