Cetuximab

• Metastatic Colorectal Cancer (mCRC):
  For treatment of EGFR-expressing, KRAS wild-type metastatic colorectal cancer, either as monotherapy after failure of chemotherapy or in combination with irinotecan-based chemotherapy.
• Head and Neck Squamous Cell Carcinoma (HNSCC):
  For locally or regionally advanced squamous cell carcinoma of the head and neck, in combination with radiation therapy or as monotherapy in recurrent or metastatic disease after platinum-based therapy failure.
• Off-label Uses:
  Occasionally used in other EGFR-expressing tumors under investigational protocols.

• Route: Intravenous infusion.
• Loading Dose:
  400 mg/m² administered as an intravenous infusion over 120 minutes on Day 1.
• Maintenance Dose:
  250 mg/m² administered weekly as intravenous infusion over 60 minutes.
• Dose Adjustments:
• Infusion-related reactions: Slow or interrupt infusion; premedication may be used.
• Skin toxicity: Dose reductions or interruptions may be needed depending on severity.
• Duration:
  Continue until disease progression or unacceptable toxicity.
• Special Populations:
  No dose adjustment for mild to moderate renal or hepatic impairment; insufficient data in severe impairment.

Cetuximab is a chimeric (mouse/human) monoclonal antibody that specifically binds to the extracellular domain of the epidermal growth factor receptor (EGFR), blocking ligand binding and receptor activation. This inhibits downstream signaling pathways involved in cellular proliferation, angiogenesis, metastasis, and survival. Cetuximab also induces antibody-dependent cellular cytotoxicity (ADCC), enhancing immune-mediated tumor cell killing, leading to inhibition of tumor growth in EGFR-expressing cancers.

• Absorption:
  Administered intravenously; 100% bioavailability.
• Distribution:
  Volume of distribution approximately 3.2 L (close to plasma volume).
• Metabolism:
  Catabolized into small peptides and amino acids via nonspecific proteolytic pathways.
• Elimination:
  Half-life approximately 112 hours (4.7 days), allowing weekly dosing.
• Steady-State:
  Achieved by the second week of treatment.

• Pregnancy:
  Category C — animal studies show adverse effects; no adequate human studies. Use only if benefit justifies risk.
• Lactation:
  Unknown if excreted in human milk; breastfeeding not recommended during treatment.

• Antineoplastic agent
• Monoclonal antibody targeting EGFR

• Known hypersensitivity to cetuximab or any murine proteins.
• History of severe infusion-related reactions.

• Infusion Reactions:
  Severe and potentially fatal reactions may occur, especially during the first infusion. Monitor closely; premedicate with antihistamines.
• Cardiopulmonary Arrest and Interstitial Lung Disease:
  Rare but serious events reported; monitor for respiratory symptoms.
• Dermatologic Toxicity:
  Acneiform rash is common; may require dose modification.
• Electrolyte Abnormalities:
  Hypomagnesemia, hypokalemia, hypocalcemia may occur; monitor electrolytes regularly.
• Pulmonary Toxicity:
  Monitor for interstitial lung disease signs.

Common:

• Acneiform rash
• Infusion-related reactions (fever, chills, hypotension)
• Diarrhea
• Fatigue
• Hypomagnesemia

Serious/Rare:

• Severe infusion reactions/anaphylaxis
• Interstitial lung disease
• Cardiopulmonary arrest
• Electrolyte disturbances requiring supplementation

• No formal CYP450 interactions.
• Potential additive toxicity with other chemotherapeutic agents.
• Avoid live vaccines during treatment.

• Updated guidelines recommend KRAS wild-type status confirmation prior to use in colorectal cancer.
• Newer data support early management of skin toxicity to improve adherence.
• EMA and FDA continue to monitor rare pulmonary and cardiac events.

• Store refrigerated at 2°C to 8°C (36°F to 46°F).
• Protect from light.
• Do not freeze.
• Use immediately after dilution; if not, store diluted solution refrigerated and use within manufacturer-recommended timeframe.
• Keep vial in original carton until use.
• Keep out of reach of children.