Cetuximab in Head and Neck Oncology

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Mechanism of Action:
    • Target:
      • Cetuximab is a chimeric monoclonal IgG1 antibody directed against the epidermal growth factor receptor (EGFR / ErbB1)
    • Binding: 
      • It binds with higher affinity than natural ligands (EGF, TGF-α):
        • Blocking ligand-induced EGFR activation
    • Downstream effects:
      • Inhibition of EGFR autophosphorylation → suppression of downstream pathways (RAS / RAF / MEK / ERK and PI3K / AKT) → reduced proliferation and survival
      • Induces cell cycle arrest and apoptosis.
      • Inhibits angiogenesis:
        • Via VEGF downregulation
      • Enhances radiosensitivity and chemosensitivity
      • Triggers antibody-dependent cellular cytotoxicity (ADCC):
        • Due to IgG1 Fc interaction with NK cells
  • Indications in Head & Neck Oncology:
    • Locally Advanced Head & Neck Squamous Cell Carcinoma (HNSCC):
      • In combination with definitive radiotherapy in patients not suitable for high-dose cisplatin
      • Based on the Bonner trial (NEJM 2006):
        • Cetuximab + RT improved locoregional control and OS compared with RT alone
    • Recurrent or Metastatic HNSCC:
      • First-line (EXTREME regimen): 
        • Cetuximab + platinum (cisplatin / carboplatin) + 5-FU:
          • Demonstrated OS benefit (Vermorken et al., NEJM 2008)
      • As monotherapy or maintenance:
        • In platinum-refractory or palliative setting
    • Special Situations:
      • Considered for cisplatin-ineligible patients
      • Investigated in combination with immunotherapy (e.g., PD-1 inhibitors), though data are evolving
  • Adverse Effects:
    • Dermatologic (most common):
      • Acneiform rash (papulopustular eruption) in ~ 80%:
        • Correlates with better response
      • Xerosis, pruritus, paronychia
    • Infusion-related reactions:
      • Fever, chills, bronchospasm, hypotension
      • Severe (anaphylaxis-like) reactions more common in the Southeastern US:
        • Linked to preexisting IgE antibodies against galactose-α-1,3-galactose from tick bites
    • Electrolyte disturbances:
      • Hypomagnesemia:
        • Due to renal Mg wasting
      • Hypokalemia
      • Hypocalcemia
    • Other:
      • Diarrhea, mucositis, fatigue
    • Rare:
      • Interstitial lung disease, cardiotoxicity
  • Management of Adverse Effects:
    • Skin toxicities:
      • Prophylaxis:
        • Sunscreen, moisturizers, topical steroids, oral tetracyclines (doxycycline / minocycline)
      • Management:
        • Topical antibiotics (clindamycin), systemic tetracyclines; dose modification for grade ≥ 3 rash
    • Infusion reactions:
      • Premedication:
        • H1 antihistamines ± corticosteroids
      • Severe reactions:
        • Immediate discontinuation, epinephrine, airway support
    • Electrolyte disturbances:
      • Routine monitoring of Mg, K, Ca during therapy and up to 8 weeks post-treatment
      • Oral / IV replacement as needed
  • References:
    • Bonner JA et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. NEJM. 2006;354:567–78.
    • Vermorken JB et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. NEJM. 2008;359:1116–27.
    • NCCN Guidelines: Head and Neck Cancers. Version 2025.
      Cohen EEW et al. Cetuximab in HNSCC: updated evidence. JCO.
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Published by Rodrigo Arrangoiz MS, MD, FACS, FSSO

My name is Rodrigo Arrangoiz I am a breast surgeon/ thyroid surgeon / parathyroid surgeon / head and neck surgeon / surgical oncologist that works at Center for Advanced Surgical Oncology in Miami, Florida. I was trained as a surgeon at Michigan State University from (2005 to 2010) where I was a chief resident in 2010. My surgical oncology and head and neck training was performed at the Fox Chase Cancer Center in Philadelphia from 2010 to 2012. At the same time I underwent a masters in science (Clinical research for health professionals) at the University of Drexel. Through the International Federation of Head and Neck Societies / Memorial Sloan Kettering Cancer Center I performed a two year head and neck surgery and oncology / endocrine fellowship that ended in 2016. Mi nombre es Rodrigo Arrangoiz, soy cirujano oncólogo / cirujano de tumores de cabeza y cuello / cirujano endocrino que trabaja Center for Advanced Surgical Oncology en Miami, Florida. Fui entrenado como cirujano en Michigan State University (2005 a 2010 ) donde fui jefe de residentes en 2010. Mi formación en oncología quirúrgica y e n tumores de cabeza y cuello se realizó en el Fox Chase Cancer Center en Filadelfia de 2010 a 2012. Al mismo tiempo, me sometí a una maestría en ciencias (investigación clínica para profesionales de la salud) en la Universidad de Drexel. A través de la Federación Internacional de Sociedades de Cabeza y Cuello / Memorial Sloan Kettering Cancer Center realicé una sub especialidad en cirugía de cabeza y cuello / cirugia endocrina de dos años que terminó en 2016.

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