Topoisomerase Inhibitors

Question 1

Etoposide

Answer 1

Epipodophyllotoxins (Topo II inhibitor)
- Topo II inhibitor- creates a cleavable DNA complex
- 50% oral avail, liver metab, renal excretion
Tox: N/V
- Myelosuppression
- Hypotension
- Alopecia

Question 2

Capothecins

Answer 2

Topo I Inhibitors

- Topo I cuts and relegates SS DNA strands- inhibition of TOPO I causes DNA damage and S-Phase arrest

Question 3

Topotecan

Answer 3

Topo I Inhibitor
- IV Infusion, renal excretion 
- Tx for SCLC
Tox: - N/V
- Alopecia
- BM Suppression- neutropenia

Question 4

Irinotecan

Answer 4

Topo I inhibitor

• ProDrug- converted in liver to SN-38 metabolite which is 100X more potent than the drug
• Excretion in bile/feces
• 1st line tx for CRC
• DIARRHEA (I ran to the can!)
• Early- cholinergic, Late- 2-10 days post- tx can be severe
• BM suppression