Agents that induce structural DNA damage (Alkylating, Platinum)

Question 1

Cyclophosphamide

Answer 1

Type: Alkylating Agent

MOA: Alkylate DNA –> strand breaks –> (p53) –> apoptosis

AE:
1. Hemorrhagic cystitis (due to formation of acrolein)
–Prevention: Extensive hydration, MESNA (binds to acrolein)

2. Secondary Malignancies
3. Gonadotoxic

Question 2

Cisplatin

Answer 2

Type: Platinum Agents

MOA: forms platinum adducts to crosslink guanines –> apoptosis

AE:
1. Nephtotoxicity (extensively cleared by kidneys)
–Damage to TAL: decreases GFR, K, Mg (moniter Mg, K, SCr)
–Presentation: Hypomagnesemia
Prevention: Hydration, Amitostin

2. Ototoxicity (tinnitus, hearing loss)