II. Indications

  1. Colorectal Cancer (metastatic, wild-type K-RAS, EGFR positive)
    1. Cetuximab
    2. Panitumumab
  2. Squamous cell cancer of the head and neck
    1. Cetuximab
  3. Non-Small Cell Lung Cancer (metastatic, squamous cell)
    1. Necitumumab
    2. Cetuximab (off-label)
  4. Squamous Cell Skin Cancer (non-resectable)
    1. Cetuximab (off-label)

III. Mechanism

  1. Epidermal Growth Factor Receptor (EGFR, HER1)
    1. EGFR is Tyrosine Kinase that is activated by specific Ligands on cells of epidermal-lineage
    2. Binding triggers cascade that leads to epithelial cell growth, development and homeostasis
    3. May also trigger cancer cell proliferation, invasion and migration
      1. EGFR Tyrosine Kinase mutations and amplifications
      2. Seen in a variety of cancers (e.g. lung, Breast, brain)
  2. EGFR Monoclonal Antibody
    1. Recombinant, chimeric Monoclonal Antibody targeting Epidermal Growth Factor Receptor (EGFR, HER1)
    2. Binds extracellular EGFR on the cell surface preventing receptor binding and activation
    3. Cetuximab (Erbitux): Used in Colon Cancer and head and neck tumors
    4. Panitumumab (Vectibix): Used in Colon Cancer
    5. EGFR agents have been effective in metastatic Colorectal Cancer (without RAS mutation)
  3. Other agents targeting EGFR
    1. Small Molecule EGFR Inhibitor

IV. Medications

  1. Cetuximab (Erbitux) IV Solution
    1. Risk of Anaphylaxis, Cardiac Arrest, infusion reaction, lung toxicity, Pulmonary Embolism, Renal Failure, Sepsis
    2. Also risk of skin rash including exfoliation (95% of patients, severe in 16%)
  2. Necitumumab (Portrazza) IV Solution
    1. Risk of Cardiac Arrest, infusion reaction, arterial thrombosis, Pulmonary Embolism, severe dermatitis
  3. Panitumumab (Vectibix) IV Solution
    1. Risk of Anaphylaxis, infusion reaction, ocular toxicity, lung toxicity, dermatitis (90% of patients, 15% severe)

V. Dosing

  1. See other references for disease specific dosing protocols

VI. Adverse Effects

  1. Cardiopulmonary
    1. Cardiac Arrest (FDA black box, Cetuximab, Necitumumab)
    2. Serious infusion reaction including fatal reactions (Cetuximab, Necitumumab, Panitumumab)
    3. Lung toxicity including intersititial lung disease or pulmonary fibrosis (Cetuximab, Panitumumab)
    4. Pulmonary Embolism (Cetuximab, Necitumumab)
    5. Arterial Thrombosis (Necitumumab)
  2. Dermatologic
    1. Skin rash including exfoliation (Cetuximab, , Necitumumab, Panitumumab )
    2. Dermatitis often is an indicator that the EGFR Inhibitor is working
    3. Acne
  3. Gastrointestinal
    1. Diarrhea occurs in 50% of patients on EGFR Inhibitors
  4. Renal
    1. Acute Kidney Injury (Cetuximab)
    2. Hypomagnesemia (Cetuximab, Necitumumab)
  5. Eye
    1. Ocular toxicity including Keratitis and Corneal perforation (Panitumumab)

VII. Safety

  1. Avoid in Lactation
  2. Avoid in pregnancy (all trimesters, Pregnancy category X)
    1. Use reliable Contraception
  3. Monitoring
    1. Serum Electrolytes (during treatment and for 8 weeks after)
      1. Serum Magnesium
      2. Serum Potassium
      3. Serum Calcium

Images: Related links to external sites (from Bing)

Related Studies