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,
  • 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,
  • 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

• Aluminum toxicity
• Antimony toxicity
• Arsenic toxicity
• Barium toxicity
• Bismuth toxicity
• Cadmium toxicity
• Chromium toxicity
• Cobalt toxicity
• Copper toxicity
• Gold toxicity
• Iron toxicity
• Lead toxicity
• Lithium toxicity
• Manganese toxicity
• Mercury toxicity
• Nickel toxicity
• Phosphorus toxicity
• Platinum toxicity
• Selenium toxicity
• Silver toxicity
• Thallium toxicity
• Tin toxicity
• Zinc toxicity

Evaluation

• CBC, BMP, Mg/Phos, LFTs, UA
• Serum platinum levels
  • 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
  • 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