Epipodophyllotoxins

Class: Topoisomerase II inhibitors (plant-derived podophyllotoxin derivatives).

• Key Drugs:
  • Etoposide (VP-16) – IV or oral.
  • Teniposide (VM-26) – IV.

Mechanism of Action

• Inhibit topoisomerase II → prevent relegation of DNA double-strand breaks → accumulation of DNA damage → apoptosis.
• Cell cycle specific to late S and G2 phases.

Clinical Uses

• Etoposide:
  • Small cell lung cancer (SCLC), testicular cancer, lymphoma, AML (part of combination regimens).
  • Pediatric tumors: neuroblastoma, Ewing sarcoma.
• Teniposide:
  • Pediatric ALL, some lymphomas.
• Often combined with platinum agents or other cytotoxics.

Dosing

• Etoposide (IV): 50–100 mg/m²/day for 3–5 days (depends on regimen).
• Etoposide (PO): 100–200 mg/m²/day × 3–5 days.
• Teniposide (IV): 50–200 mg/m²/day × 1–5 days, depending on protocol.
• Dose adjustment needed for renal and hepatic impairment.

Toxicities

• Myelosuppression – neutropenia and thrombocytopenia (dose-limiting).
• Nausea, vomiting, mucositis, alopecia.
• Hypotension during IV infusion (especially rapid infusion of etoposide).
• Secondary leukemia (t-AML), especially with high cumulative doses or prior alkylator therapy.
• Rare: hepatotoxicity, infusion reactions.

Monitoring

• CBC before and during therapy.
• Renal and hepatic function tests.
• Vital signs during infusion (etoposide hypotension risk).
• Cumulative dose to reduce t-AML risk.

In summary:

Epipodophyllotoxins (etoposide, teniposide) are topo II inhibitors, late S/G2 phase–specific, widely used in SCLC, testicular cancer, lymphoma, and pediatric tumors. Main concerns are myelosuppression, infusion-related hypotension, and secondary leukemia.