Squamous Cell Carcinoma of the Head and Neck (SCCHN): Cetuximab is used in combination with radiation therapy for the initial treatment of patients with locally or regionally advanced squamous cell carcinoma of the head and neck.

Cetuximab is also indicated in combination with platinum-based chemotherapy and 5-fluorouracil (5-FU) as first-line treatment for patients with recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck.

As a single agent, Cetuximab is used in patients with recurrent or metastatic squamous cell carcinoma of the head and neck who have not responded to prior platinum-based therapy.

K-Ras Wild-Type, EGFR-Expressing Colorectal Cancer: Cetuximab is indicated for the treatment of K-Ras wild-type, EGFR-expressing metastatic colorectal cancer (mCRC), as confirmed by approved diagnostic tests:

• In combination with FOLFIRI (irinotecan, 5-fluorouracil, leucovorin) for first-line treatment
• In combination with irinotecan in patients resistant to irinotecan-based chemotherapy
• As monotherapy in patients who have failed oxaliplatin- and irinotecan-based chemotherapy or are intolerant to irinotecan

Cetuximab is a recombinant chimeric monoclonal antibody derived from human and mouse sources. It specifically binds to the epidermal growth factor receptor (EGFR), thereby blocking the binding of epidermal growth factor (EGF) and other ligands. This inhibition prevents receptor activation and phosphorylation, leading to suppression of cell proliferation, induction of apoptosis, and reduction in matrix metalloproteinase and vascular endothelial growth factor (VEGF) production.

Squamous Cell Carcinoma Of The Head And Neck:
Cetuximab in combination with radiation therapy or in combination with platinum-based therapy with 5-FU:

• The recommended initial dose is 400 mg/m² administered one week prior to initiation of a course of radiation therapy or on the day of initiation of platinum-based therapy with 5-FU as a 120-minute intravenous infusion (maximum infusion rate 10 mg/min). Complete Cetuximab administration 1 hour prior to platinum-based therapy with 5-FU.
• The recommended subsequent weekly dose (all other infusions) is 250 mg/m² infused over 60 minutes (maximum infusion rate 10 mg/min) for the duration of radiation therapy (6–7 weeks) or until disease progression or unacceptable toxicity when administered in combination with platinum-based therapy with 5-FU. Complete Cetuximab administration 1 hour prior to radiation therapy or platinum-based therapy with 5-FU.

Cetuximab monotherapy:

• The recommended initial dose is 400 mg/m² administered as a 120-minute intravenous infusion (maximum infusion rate 10 mg/min).
• The recommended subsequent weekly dose (all other infusions) is 250 mg/m² infused over 60 minutes (maximum infusion rate 10 mg/min) until disease progression or unacceptable toxicity.

Colorectal Cancer:

• Determine EGFR-expression status using FDA-approved tests prior to initiating treatment. Also confirm the absence of a Ras mutation prior to initiation of treatment with Cetuximab.
• The recommended initial dose, either as monotherapy or in combination with irinotecan or FOLFIRI (irinotecan, 5-fluorouracil, leucovorin), is 400 mg/m² administered as a 120-minute intravenous infusion (maximum infusion rate 10 mg/min). Complete Cetuximab administration 1 hour prior to FOLFIRI.
• The recommended subsequent weekly dose, either as monotherapy or in combination with irinotecan or FOLFIRI, is 250 mg/m² infused over 60 minutes (maximum infusion rate 10 mg/min) until disease progression or unacceptable toxicity. Complete Cetuximab administration 1 hour prior to FOLFIRI.

Recommended Premedication: Premedicate with an H1 antagonist (eg, 50 mg of diphenhydramine) intravenously 30–60 minutes prior to the first dose; premedication should be administered for subsequent Cetuximab doses based upon clinical judgment and presence/severity of prior infusion reactions.

Administration

Do not administer cetuximab as an intravenous push or bolus. Administer via infusion pump or syringe pump. Do not exceed an infusion rate of 10 mg/min. Administer through a low protein binding 0.22-micrometer in-line filter.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The solution should be clear and colorless and may contain a small amount of easily visible, white, amorphous, cetuximab particulates. Do not shake or dilute.

Fatigue, pain, headache, fever, confusion, anxiety, insomnia, chills, rigors, depression. Acne-like rash, skin rash, dry skin, itching, nail changes, hypomagnesemia, abdominal pain, constipation, diarrhea, vomiting, nausea, weight loss, weakness, bone pain.

Pregnancy: Category C. Animal studies have shown adverse effects on the fetus, and there are no adequate and well-controlled studies in pregnant women. The drug should be used only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers: It is unknown whether Cetuximab is excreted in human milk. As IgG antibodies may pass into breast milk and due to the risk of serious adverse reactions in infants, a decision should be made to discontinue either breastfeeding or the drug. If breastfeeding is stopped, it should not be resumed earlier than 60 days after the last dose.

Reduce infusion rate if signs of toxicity appear. Discontinue therapy in case of severe infusion reactions. Use with caution in patients with a history of coronary artery disease, heart failure, or arrhythmias. Monitor serum electrolytes during treatment and for at least 8 weeks afterward. Sun exposure may worsen skin reactions. Patients with pre-existing lung disease may have an increased risk of interstitial lung disease. Adjust dose if severe acneiform rash develops, following recommended guidelines.

Dose adjustment in cases of severe acneiform rash (Grade 3 or 4):

• 1st occurrence: Delay infusion for 1–2 weeks. If improvement occurs, resume at 250 mg/m²; discontinue if no improvement.
• 2nd occurrence: Delay infusion for 1–2 weeks. If improved, resume at reduced dose of 200 mg/m²; discontinue if no improvement.
• 3rd occurrence: Delay infusion for 1–2 weeks. If improved, resume at reduced dose of 150 mg/m²; discontinue if no improvement.
• 4th occurrence: Discontinue therapy permanently.

A maximum single dose of 1000 mg/m² has been reported without associated adverse events.

Targeted Cancer Therapy

Store vials in a refrigerator at 2°C to 8°C. Do not freeze.