Cyclophosphamide is a prodrug which is converted in the body to the active metabolites. It acts at any stage of the cell cycle. It prevents cell division by cross-linking deoxyribonucleic acid (DNA) strands and reducing DNA synthesis. It also exerts a potent immunosuppressive effect.

Malignant Diseases:

Cyclophosphamide is indicated for the treatment of:

• Malignant lymphomas (Stages III and IV of the Ann Arbor staging system), Hodgkin's disease, lymphocytic lymphoma (nodular or diffuse), mixed-cell type lymphoma, histiocytic lymphoma, Burkitt's lymphoma
• Multiple myeloma
• Leukemias: chronic lymphocytic leukemia, chronic granulocytic leukemia (it is usually ineffective in acute blastic crisis), acute myelogenousand monocytic leukemia, acute lymphoblastic (stem-cell) leukemia (cyclophosphamide given during remission is effective in prolonging its duration)
• Mycosis fungoides (advanced disease)
• Neuroblastoma (disseminated disease)
• Adenocarcinoma of the ovary
• Retinoblastoma
• Carcinoma of the breast

Cyclophosphamide, although effective alone in susceptible malignancies, is more frequently used concurrently or sequentially with other antineoplastic drugs.

Minimal Change Nephrotic Syndrome in Pediatric Patients:

Cyclophosphamide is indicated for the treatment of biopsy proven minimal change nephrotic syndrome in pediatrics patients who failed to adequately respond to or are unable to tolerate adrenocorticosteroid therapy.

Intravenous (Adult)-

Malignancies: 

• Low dose regimen: 2-6 mg/kg wkly as a single dose;
• Moderate dose regimen: 10-15 mg/kg wkly as a single dose;
• High dose regimen: 20-40 mg/kg as a single dose every 10-20 days.

Alternatively,

• 80-300 mg/m² daily as a single dose, or
• 300-600 mg/m² wkly as a single dose, or
• 600-1,500 mg/m² as a single dose or
• Short infusion at 10- to 20-day intervals.

Oral (Child)-

Nephrotic syndrome: 

• 2 mg/kg daily for 8-12 wk.
• Max cumulative dose: 168 mg/kg.
• Max duration: 90 days.

Oral (Adult)-

Malignancies: 

• Low dose regimen: 2-6 mg/kg wkly in divided dose.
• Alternatively, 100-300 mg daily in divided doses, or
• 50-250 mg/m² daily or 80-300 mg/m² daily in divided doses.

Administration

Should be taken on an empty stomach. Preferably taken on an empty stomach, but may be taken with meals to minimise GI irritation. Ensure adequate fluid intake. Swallow whole.

Patient with bone marrow aplasia, urinary outflow obstruction, UTI, acute infection, drug- or radiation-induced urothelial toxicity. Pregnancy.

Alopecia, skin and nails hyperpigmentation, nausea and vomiting, mucositis, inappropriate antidiuretic hormone secretion, carbohydrate metabolism disturbances, gonadal suppression, interstitial pulmonary fibrosis.

Overdose Effects

Symptoms: Urotoxicity, myelosuppression, cardiotoxicity (including cardiac failure), stomatitis, veno-occlusive hepatic disease.

Management: Supportive treatment. May consider haemodialysis. Cystitis prophylaxis with mesna may be useful for urotoxicity.

Patient with DM, severe immunosuppression, acute porphyria, pre-existing CV disease or those at risk for cardiotoxicity. Renal and hepatic impairment. Lactation.

Pregnancy & Lactation

Pregnancy Category D. There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).