Platinum toxicity

Background

  • Most often due to platinum-based anti-neoplastic drugs (e.g. cisplatin, carboplatin)
  • Can also occur with occupational exposure (skin or dust inhalation) to platinum-soluble salts, used as industrial catalysts and in some specialized photographic processes
  • Cytotoxicity results when platinum-containing complexes form inter or intra-strand platinum-DNA cross-linkages

Clinical Features

  • Platinum based chemotherapy toxicity[1],[2]
    • Peripheral and cranial neuropathy (ototoxicity, optic neuropathy): common, often permanent
    • Nephrotoxicity: dose-limiting toxicity
      • Multifactorial, typically prevented with forced diuresis
      • Electrolyte abnormalities due to tubular damage; in particular renal salt wasting syndrome
    • Mucositis,nausea/vomiting
    • Hepatic steatosis
    • Mild=moderate myelosuppression
  • Occupational exposure[3],[4]
    • History of exposure to platinum=soluble salts, such as sodium chloroplatinate, ammonium chloroplatinate, platinum tetrachloride
    • Dust can sensitize airways, trigger Asthma/reactive airway symptoms
    • Dermatitis
    • Irritating to eyes, mucous membranes
    • Metallic platinum usually does not typically cause similar effects

Differential Diagnosis

Heavy metal toxicity

Evaluation

  • CBC, BMP, Mg/Phos, LFTs, UA
  • Serum platinum levels[5]
    • Unexposed: <0.04mcg/ml
    • Peak levels during platinum-based chemotherapy: 0.6-1.8mcg/mL
    • Increased risk of toxicity if >1.8mcg/ml

Management

  • Decontaminate if occupational exposure
  • Predominantly supportive/symptomatic treatment
  • Volume resuscitate if AKI, correct electrolyte abnormalities
  • Respiratory support, bronchodilators if needed for inhalational exposure
  • Sodium thiosulfate: for cisplatin overdose[6]
    • Binds free platinum to form nontoxic thiosulfate-cisplatin complex, prevents renal tubule damage
    • Binds to free platinum to form a nontoxic thiosulfate-cisplatin complex, limits renal tubular damage
    • 4g/m2 IV bolus over 15m within 1-2h of overose, then 12g/m2 infusion over 6h
    • Continue maintenance dosing until urinary platinum levels < 1mcg/mL

Disposition

See Also

External Links

References

  1. Principles of Critical Care, 4e
  2. UpToDate
  3. Poisoning & Drug Overdose, 7e
  4. NIOSH Pocket Guide to Chemical Hazards
  5. https://www.mayocliniclabs.com/test-catalog/Clinical+and+Interpretive/61749
  6. Poisoning & Drug Overdose, 7e

Authors:

Claire