Platinum compounds

• Platinum compounds includes cisplatin, carboplatin, and oxaliplatin.
• Oxaliplatin does not cause cross-resistant with cisplatin and carboplatin
• MOA of platinum compounds is similar as alkylating agents.

  (1) cause inter- and intra-strand cross-linkage (or)

  (2) adults (brings together) between neighboring guanines

  • leads to (a) denatures of DNA helix (b) ihibition of DNA synthesis & function
• Toxicity of cisplastin include mild hematologic toxicity, ototoxicity, neurotoxicity, nephrotoxicity, N&V
• (Cisplatin): Ototoxicity

  1. audiograms shows bilateral symmetrical high frequency hearing loss, irreversible
  2. Cautions with aminoglycosides - have same SE
• (Cisplatin): Nephrotoxicity

  1. concentration is high in kidney than plasma, reversible
  2. initiating event: proximal tubule lesion
  3. secondary event: disturbances in distal tubular reabsorption, renal vascular resistance, renal blood flow, glomerular filtration, polyuria (seen in 2-3 days later)
  4. Hypomagnesemia
• (Cisplatin): The preventive measures of nephrotoxicity include

  1. aggressive saline hydration, before and after infusion to enhance the excretion
  2. magnesium supplementation
• (Cisplatin): Predisposing factors of nephrotoxicity

  1. >60 years
  2. higher dose
  3. cumulative dose
  4. low albumin
  5. pretreatmet: GFR < 75MmL/min
• Toxicity of oxaliplatin includes GIT toxicity, minimal hematologic toxicity, peripheral neuropathy, mild hypersensitivity reaction.
• Oxaliplain has NO nephrotoxicity
• Carboplatin has hematologic toxicity > cisplatin and oxaliplatin