Platinum Compounds

PLATINUM COMPOUNDS


PLATINUM COMPOUNDS

Drugs: Cisplatin, carboplatin & oxaliplatin.

MOA:

  • Similar to alkylating agents.
  • Acts on both resting & dividing cells.
  • Platinum acts on nucleophilic groups on DNA bases –> Leading to cross-linking of bases, abnormal base-pairing  & DNA strand breakage.

Adverse effect:

  • Most common – Nausea & vomiting (maximum among all anti-cancer drugs).
  • Nephrotoxic, ototoxic & neurotoxic.
    • Cisplatin – Most nephrotoxic.
    • Carboplatin – More hematotoxicity.
  • Mild bone marrow suppression.

Individual drug details:

I) Cisplatin:

Adverse effect:

1. Most nephrotoxic.

  • Prior to cisplatin therapy – Establish chloride diuresis to prevent renal toxicity.
  • Chloride diuresis – No effect on ototoxicity.
  • Amifostine – Reduces cisplatin-induced nephrotoxicity.

2. Reduces all serum ions – Causes hypomagnesemia, hypokalemia, hypocalcemia & hypophosphatemia.

3. On long-term treatment (>4yrs) – AML development.

4. Bone marrow suppression (less incidence).

Note on Amifostine: Treats xerostomia during irradiation of head & neck (involving parotid).

Cisplatin administration instructions:

  • Always slow i.v. infusion (never bolus) – To prevent intense nausea & acute rise in serum creatinine.
  • Aluminum-containing equipment/needles should not be used with cisplatin – Aluminium inactivates cisplatin.

Carboplatin:

  • More hematotoxic (bone marrow suppressant).
  • Less nephrotoxic, ototoxic & neurotoxic potential than cisplatin.

Oxaliplatin:

  • Effective against cisplatin/carboplatin resistant cells.
  • Adverse effects:
    • Neurotoxicity (peripheral neuropathy) – Dose-limiting toxicity.

Exam Important

  • Cisplatin, carboplatin & oxaliplatin are platinum compounds.
  • Most common adverse effect of platinum compounds is Nausea & vomiting which is maximum among all anti-cancer drugs.
  • Nephrotoxic, ototoxic & neurotoxic are all caused by platinum compounds.
  • Cisplatin is the most nephrotoxic.
  • Carboplatin is the more hematotoxicity.
  • Prior to cisplatin therapy, it is essential to establish chloride diuresis, to prevent renal toxicity.
  • Amifostine reduces cisplatin-induced nephrotoxicity.
  • Cisplatin reduces all serum ions & causes hypomagnesemia, hypokalemia, hypocalcemia & hypophosphatemia.
  • On long-term treatment (>4yrs) cisplatin can cause AML development.
  • Amifostine is used to xerostomia during irradiation of head & neck (involving parotid).
  • Cisplatin administered as slow i.v. infusion (never bolus), to prevent intense nausea & acute rise in serum creatinine.
  • Carboplatin is more hematotoxic (bone marrow suppressant), but less nephrotoxic, ototoxic & neurotoxic than cisplatin.
  • Oxaliplatin is effective against cisplatin/carboplatin resistant cells but causes neurotoxicity (peripheral neuropathy), which is a dose-limiting toxicity.
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