Drug Class: Topoisomerase II inhibitor; semisynthetic podophyllotoxin derivative
Mechanism of Action
Inhibits topoisomerase II, preventing the re-ligation of DNA double-strand breaks during replication. This leads to accumulation of DNA damage → cell cycle arrest in late S and G₂ phase → apoptosis.
Indications
- Small cell lung cancer (SCLC) – often in combination with platinum agents
- Testicular cancer – part of BEP or EP regimens
- Other uses: lymphomas, acute leukemias, Ewing sarcoma, ovarian cancer, gastric cancer
Formulations: IV solution (etoposide phosphate also available), oral capsules (50% bioavailability → oral dose ≈ 2× IV dose)
Adult Dosing
- Testicular cancer: 100 mg/m² IV daily × 5 days (BEP/EP cycles)
- SCLC: 100–120 mg/m² IV daily × 3 days with platinum agent
- Dose adjusted for indication, route, and organ function.
Pediatric Dosing: Commonly 100–150 mg/m²/day IV × 3–5 days depending on protocol.
Renal Dose Adjustment
- CrCl 15–50 mL/min → 75% of usual dose
- CrCl <15 mL/min → 50% of usual dose
- Hemodialysis → avoid or give post-dialysis
Hepatic Dose Adjustment: Consider dose reduction if bilirubin >1.5–3× ULN or AST >3× ULN.
- Bioavailability ~50% (oral)
- t½ ~4–11 h
- Metabolism: hepatic (CYP3A4) & renal excretion (~40% unchanged in urine)
Key Toxicities
- Myelosuppression (dose-limiting; neutropenia > thrombocytopenia)
- Alopecia
- Mucositis
- Hypotension with rapid infusion (must infuse ≥30–60 min)
- Secondary leukemia (rare, alkylator-like AML, 2–3 years post-treatment)
- Nausea/vomiting (moderate, higher with high-dose)
Drug Interactions
- CYP3A4 inducers/inhibitors alter exposure
- Concurrent nephrotoxic drugs ↑ toxicity risk
Monitoring
- CBC prior to each cycle
- Renal and hepatic function
- Blood pressure during infusion
Counseling Points
- Oral doses should be taken on an empty stomach
- Report fever or infection signs promptly
- Avoid live vaccines during therapy
Clinical Pearls
- Infusion-related hypotension risk is rate-dependent → slow infusion
- Oral dosing requires doubling the IV dose for equivalent exposure
- Etoposide phosphate is water-soluble, avoiding precipitation issues and hypersensitivity from polysorbate 80