- Class: Alkylating agent – nitrogen mustard (nitrogen mustard derivative, cytotoxic).
- Type: IV cytotoxic chemotherapy.
Mechanism of Action (MOA)
- Prodrug activated by hepatic CYP450 enzymes to form active alkylating metabolites (e.g., isophosphoramide mustard).
- Forms DNA cross-links → inhibits DNA replication and transcription → cell death.
- Cell cycle non-specific, but more active in rapidly dividing cells.
Clinical Uses
- Soft tissue sarcomas – e.g., rhabdomyosarcoma, Ewing’s sarcoma.
- Testicular cancer – in combination regimens.
- Lymphomas – some refractory cases.
- Other solid tumors – off-label for various sarcomas and malignancies.
Dosing (Adults)
- Typical regimen: 1.2–1.5 g/m² IV daily for 3–5 days per cycle.
- Often given with mesna to prevent hemorrhagic cystitis.
- Dose adjustments: renal impairment, hepatic impairment, or elderly patients.
Toxicities
- Hematologic: neutropenia, thrombocytopenia, anemia – dose-limiting.
- Urotoxicity: hemorrhagic cystitis – prevented with mesna and hydration.
- Neurotoxicity: encephalopathy, confusion, somnolence – can be reversible.
- Nausea, vomiting, alopecia.
- Rare: nephrotoxicity, cardiotoxicity (high doses), secondary malignancy.
Monitoring
- CBC with differential.
- Renal function (BUN, creatinine) – monitor hydration.
- Urine output and hematuria – ensure adequate mesna coverage.
- Neurologic status – monitor for encephalopathy.
- Electrolytes, especially if prolonged therapy or hydration is used.
Summary
Ifosfamide (Ifex®) is an alkylating agent used in sarcomas, testicular cancer, and lymphomas. Key concerns are hematologic toxicity, hemorrhagic cystitis (mesna required), and neurotoxicity, with careful monitoring of CBC, renal function, urine output, and neurologic status.