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

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Related Studies

Ontology: panitumumab (C0879427)

Definition (NCI_NCI-GLOSS) A human monoclonal antibody that is being used to treat colorectal cancer that has spread to other parts of the body. It is used in patients whose disease has not gotten better during or after treatment with other anticancer drugs. It is also being studied in the treatment of other types of cancer. Monoclonal antibodies are made in the laboratory and can locate and bind to substances in the body, including cancer cells. ABX-EGF binds to the epidermal growth factor receptor (EGFR) and may block tumor cell growth.
Definition (NCI) A human monoclonal antibody produced in transgenic mice that attaches to the transmembrane epidermal growth factor (EGF) receptor. Panitumumab may inhibit autocrine EGF stimulation of tumor cells that express the EGF receptor, thereby inhibiting tumor cell proliferation.
Definition (PDQ) A human monoclonal antibody produced in transgenic mice that attaches to the transmembrane epidermal growth factor (EGF) receptor. Panitumumab may inhibit autocrine EGF stimulation of tumor cells that express the EGF receptor, thereby inhibiting tumor cell proliferation. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=37857&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=37857&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1857" NCI Thesaurus)
Concepts Amino Acid, Peptide, or Protein (T116) , Immunologic Factor (T129) , Pharmacologic Substance (T121)
MSH C500592
SnomedCT 424401006, 423259008
English panitumumab, Panitumumab, Panitumumab (substance), Panitumumab (product), Monoclonal Antibody ABX-EGF, ABX-EGF, Clone E7.6.3, panitumumab (medication), ABX-EGF monoclonal antibody, Immunoglobulin, anti-(human epidermal growth factor receptor) (human monoclonal ABX-EGF heavy chain), disulfide with human monoclonal ABX-EGF light chain, dimer, ABX-EGF MAb, PANITUMUMAB, panitumumab [Chemical/Ingredient], abx-egf, ABX-EGF, MOAB ABX-EGF, ABX-EGF Monoclonal Antibody, MoAb ABX-EGF, monoclonal antibody ABX-EGF, panitumumab antibody, human
Spanish panitumumab (sustancia), panitumumab, panitumumab (producto)

Ontology: cetuximab (C0995188)

Definition (NCI_NCI-GLOSS) A monoclonal antibody used to treat certain types of head and neck cancer, and colorectal cancer that has spread to other parts of the body. It is also being studied in the treatment of other types of cancer. Monoclonal antibodies are made in the laboratory and can locate and bind to cancer cells. Erbitux binds to the epidermal growth factor receptor (EGFR), which is found on the surface of some types of cancer cells.
Definition (NCI) A recombinant, chimeric monoclonal antibody directed against the epidermal growth factor (EGFR) with antineoplastic activity. Cetuximab binds to the extracellular domain of the EGFR, thereby preventing the activation and subsequent dimerization of the receptor; the decrease in receptor activation and dimerization may result in an inhibition in signal transduction and anti-proliferative effects. This agent may inhibit EGFR-dependent primary tumor growth and metastasis. EGFR is overexpressed on the cell surfaces of various solid tumors.
Definition (PDQ) A monoclonal antibody specific for the epidermal growth factor receptor (EGFR), a tyrosine kinase that triggers cell division. Cetuximab binds to and inhibits EGFRs, which are overexpressed on the cell surfaces of many types of tumors. This agent blocks the tumor growth, invasion, and metastasis associated with the overexpression of cell-surface EGFRs. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42384&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42384&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1723" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Immunologic Factor (T129) , Amino Acid, Peptide, or Protein (T116)
MSH C411189
SnomedCT 409401002, 409400001
English CETUXIMAB @ @ UNIDENTIFIED, CETUXIMAB UNIDENTIFIED, Chimeric Anti-EGFR Monoclonal Antibody, Immunoglobulin G1, anti-(human epidermal growth factor receptor) (human-mouse monoclonal C225 gamma1-chain), disulfide with human-mouse monoclonal C225 kappa-chain, dimer, Chimeric Monoclonal Antibody C225, Anti-Epidermal Growth Factor Receptor Monoclonal Antibody, Anti-EGFR Monoclonal Antibody, Chimeric MoAb C225, cetuximab (medication), cetuximab [Chemical/Ingredient], cetuximab, Cetuximab (product), Cetuximab (substance), Cetuximab, CETUXIMAB
Spanish cetuximab (producto), cetuximab (sustancia), cetuximab

Ontology: IMC-11F8 monoclonal antibody (C2352806)

Definition (NCI) A fully human IgG1 monoclonal antibody directed against the epidermal growth factor receptor (EGFR) with potential antineoplastic activity. Necitumumab binds to and blocks the ligand binding site of EGFR, thereby preventing the activation and subsequent dimerization of the receptor. This may lead to an inhibition of EGFR-dependent downstream pathways and so inhibition of EGFR-dependent tumor cell proliferation and metastasis. EGFR, a member of the epidermal growth factor family of extracellular protein ligands, may be overexpressed on the cell surfaces of various tumor cell types.
Concepts Immunologic Factor (T129) , Pharmacologic Substance (T121) , Amino Acid, Peptide, or Protein (T116)
MSH C527969
English IMC-11F8, IMC-11F8 monoclonal antibody, Anti-Epidermal Growth Factor Receptor Monoclonal Antibody IMC-11F8, Necitumumab, necitumumab, NECITUMUMAB