Chemotherapy

 

 

Platinum Compounds

Produce intra and interstrand crosslinks in DNA and so disrupt DNA function and replication.

Often described as Non-classical alkylating agents.

Serendipitously discovered in the 1960s during a series of experiments intended to document the effect of electromagnetic radiation on bacterial growth.

Agents in this class:

  • Cisplatin
  • Carboplatin
  • Oxaliplatin

Wide range of activity - used to treat pediatric brain tumours, neuroblastoma, osteosarcoma and Wilms tumours. In adults used to treat testicular, ovarian, head and neck, bladder, esophagus, lung, and colon cancer.

 

Cisplatin

  • given IV
  • radiation therapy sensitizer.

 

Carboplatin

  • Has similar therapeutic applications to cisplatin.
  • Better tolerated toxicity profile.
  • Most frequently used platinum agent.
  • Generally considered to be cell-cycle non-specific.

 

Oxaliplatin

  • Relatively new platinum compound.
  • Cell-cycle non-specific.
  • Approved for use in the treatment of adult colorectal cancer.

 

Summary of Platinum Compound Toxicities:

Drug Toxicity Special Considerations

Cisplatin

Moderate to severe nausea and vomiting

 

Metallic taste

 

Cumulative nephrotoxicity (azotemia and electrolyte imbalance - low Mg)

 

Neurotoxic

 

Ototoxicity (high frequency sensory neural hearing loss)

 

Mild myelosuppression
  • Premedicate with antiemetics and continue for 24-48 hours post
  • Intensifies aminoglycoside toxicity: avoid aminoglycoside administration if possible
  • Measure GFR prior to each dose
  • Maintain adequate hydration; may require replacement of negative fluid balance
  • Maintain urine output at least 2 mL.kg/hr; lasix or mannitol may be required to ensure adequate urinary output
  • Magnesium supplements routinely required
  • Provide serial audiometric testing at baseline through to follow-up
Carboplatin

Myelosuppression especially thrombocytopenia (platelet nadir 3 weeks).

 

Hypersensitivity reactions

 

Electrolyte disturbances

  • Less nephrotoxic than cisplatin, but renal function should be assessed prior to each dose
  • Thrombocytopenia is dose-limiting toxicity
  • Provide serial audiometric testing at baseline through to follow-up

Oxaliplatin

sensory neuropathy

 

Hypersensitivity reactions

 

Nausea, vomiting, diarrhea

 

Myelosuppression  
  • Monitor for hypersensitivity, anaphylaxis  reactions.  Slowing the infusion may decrease acute reactions
  • Do not mix with sodium chloride solutions
  • Avoid cold drinks and foods during administration (sensory neuropathy may be exacerbated by exposure to cold

 

 

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