Platinum Compounds

Question 1

Platinum Compound Indications

Answer 1

Testicular, ovarian, mesothelioma, head, neck, SCLC, and bladder cancers

Question 2

Changes in agent development

Answer 2

o Introduced bulky groups because with cisplatin, the chloride groups are replaced with water very fast and they stay in the renal system for a very long time (renal toxicity) → alkylating agent really quickly
o With the bulky groups carboplatin and oxaliplatin are converted much slower and don’t have the renal toxicity

Question 3

Naming of platinum compounds

Answer 3

 Cis comes from the chlorides being on the same side

 Transplatin is not a good anti-cancer drug because the chlorides are on opposite side and it doesn’t bind well

Question 4

Most common cross linking with platinum compounds

Answer 4

G-G intRAstrand 60%

A-G intRAstrand 30%

Question 5

Cisplatin Toxicity

Answer 5

Nephrotoxicity
Ototoxicity (hearing loss)
N/V

Question 6

Carboplatin Structure

Answer 6

Substituted chloride = diminished nephrotoxicity

Question 7

Carboplatin Toxicity

Answer 7

Myelosuppression and N/V

Question 8

Oxaliplatin Structure

Answer 8

Bulkier adducts and more hydrophobic

Question 9

Oxaliplatin does what kinds of crosslinking

Answer 9

Does interstrand, intrastrand and DNA-protein crosslinking

Question 10

Problem with oxaliplatin’s crosslinking?

Answer 10

Problem with protein involvement is that the proteins that recognize damaged DNA may become activated

Question 11

Oxaliplatin toxicity

Answer 11

Neurotoxicity

N/V

Question 12

Platinum Compound Resistance

Answer 12

Same as alkylating with glutathione

Question 13

Prevention of platinum compound induced AE

Answer 13

MESNA (2-mercaptoethane sulfonate)
Sodium thiosulfate
Amifostine
- Mainly with cisplatin and carboplatin