II. Indications (Part of combination protocols)

  1. FDA approved
    1. Metastatic Testicular Cancer
    2. Metastatic Ovarian Cancer
    3. Bladder Cancer
  2. Off-Label Use - Adults
    1. Cervical Cancer
    2. Endometrial Cancer
    3. Esophageal Cancer
    4. Gastric Cancer
    5. Head and neck cancer
    6. Lung Cancer (Non-small cell and small cell)
    7. Sarcoma
  3. Off-Label Use - Children
    1. Germ cell tumors
    2. Hepatoblastoma
    3. Medulloblastoma
    4. Neuroblastoma
    5. Osteosarcoma

III. Mechanism

  1. First-generation platinum based, alkylating Antineoplastic Agent
    1. Inorganic, water based compund
    2. Derived drugs include Carboplatin
  2. Components
    1. Platinum atom
    2. Ammonia groups (2)
  3. Activated via hydrolysis intracellularly to highly reactive, charged platinum complexes
    1. Binds DNA (e.g. GC rich regions)
    2. Results in DNA cross-links
    3. Results in cell growth inhibition (G2 Cell Cycle arrest), apoptosis and cell death
  4. Unique features
    1. Penetrates Testes barrier
    2. Partially penetrates blood brain barrier

IV. Medications

  1. Cisplatin IV Solution (1 mg/ml): 50 ml, 100 ml or 200 ml

V. Dosing

  1. See other references for disease specific dosing protocols

VI. Adverse Effects

  1. Alopecia
  2. Anaphylaxis
  3. Bone Marror Suppression
  4. Electrolyte abnormalities
  5. Hepatotoxicity
  6. Hyperuricemia
  7. Optic Neuritis (as well as Papilledema, cerebral blindness)
  8. Ototoxicity
    1. May be irreversible
    2. Higher risk in patients with TMPT gene variant (thiopurine-S-Methyltransferase)
  9. Myalgias
  10. Nephrotoxicity
    1. Reduced when amifostine is added to Ovarian Cancer regimen
  11. Peripheral Neuropathy
  12. Secondary Malignancy
  13. Vomiting (excessive)

VII. Safety

  1. Avoid in Lactation
  2. Pregnancy Category D
    1. Avoid in Pregnancy (all trimesters)
    2. Use reliable Contraception
  3. Age >65 years
    1. Increased risk of nephrotoxicity, Bone Marrow suppression, Peripheral Neuropathy
  4. Monitoring
    1. Complete Blood Count
    2. Electrolytes
    3. Renal Function tests
    4. Liver Function Tests
    5. Audiometry

VIII. Drug Interactions

  1. Phenytoin
    1. Cisplatin decreases levels
  2. Aminoglycosides
    1. Increased risk of nephrotoxicity

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