- Class: Alkylating agent – nitrogen mustard (oxazaphosphorine).
- Brand names: ®, others.
- Type: IV and oral cytotoxic chemotherapy.
Mechanism of Action (MOA)
- Prodrug metabolized by hepatic CYP450 enzymes to active alkylating metabolites (phosphoramide mustard, acrolein).
- Forms DNA cross-links, interfering with DNA replication and transcription → apoptosis.
- Cell cycle non-specific, preferentially affects rapidly dividing cells.
Clinical Uses
- Hematologic malignancies: leukemia, lymphoma, multiple myeloma.
- Solid tumors: breast cancer, ovarian cancer, sarcomas.
- Immunosuppressive therapy: severe autoimmune diseases (e.g., lupus nephritis, vasculitis).
- Component of conditioning regimens for bone marrow transplantation.
Dosing (Adults)
- IV: 500–1,500 mg/m² per cycle (varies with regimen).
- Oral: 1–5 mg/kg/day for certain regimens or immunosuppressive use.
- Administer with adequate hydration to reduce risk of urotoxicity.
- Mesna sometimes used for high-dose IV regimens to prevent hemorrhagic cystitis.
Toxicities
- Hematologic: myelosuppression – neutropenia, thrombocytopenia, anemia.
- Urotoxicity: hemorrhagic cystitis (due to acrolein metabolite) – prevent with hydration and mesna.
- Nausea, vomiting, alopecia.
- Gonadal toxicity → infertility risk.
- Rare: SIADH, secondary malignancies (leukemia, bladder cancer).
- Immunosuppression → infection risk.
Monitoring
- CBC with differential.
- Renal function and urine output.
- Signs of hematuria → ensure adequate hydration and mesna if indicated.
- Liver function tests (less commonly affected).
- Reproductive counseling for fertility risk.
Summary
Cyclophosphamide (Cytoxan®) is a widely used alkylating agent for malignancies and autoimmune conditions. Key concerns are myelosuppression, hemorrhagic cystitis (hydration/mesna), gonadal toxicity, and infection risk, requiring monitoring of CBC, renal function, and urine output.