cetuximab

High Alert

Locally or regionally advanced squamous cell carcinoma of the head and neck (in combination with radiation therapy).
Recurrent or metastatic squamous cell carcinoma of the head and neck progressing after platinum-based therapy.
Recurrent or metastatic squamous cell carcinoma of the head and neck (in combination with platinum-based therapy with 5-fluorouracil).
K-ras wild-type, epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer in patients who have not responded to irinotecan and oxaliplatin or are intolerant to irinotecan.
K-ras wild-type, EGFR-expressing metastatic colorectal cancer in patients who have not responded to irinotecan alone (in combination with irinotecan).
First-line treatment of K-ras wild-type, EGFR-expressing metastatic colorectal cancer (in combination with irinotecan, 5-fluorouracil, and leucovorin [FOLFIRI]).
Metastatic colorectal cancer with a BRAF V600E mutation (in combination with encorafenib).

Action ⬆ ⬇

Binds specifically to EGFR, thereby preventing the binding of endogenous epidermal growth factor. This prevents cell growth and differentiation processes.

Therapeutic effects:

Decreased tumor growth and spread.

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Minimally distributed to tissues.

Metabolism/Excretion: Unknown.

Half-Life: 97–114 hr.

Time/Action Profile ⬆ ⬇

ROUTE	ONSET	PEAK	DURATION
IV	unknown	unknown	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity to cetuximab or murine (mouse) proteins;
RAS-mutant metastatic colorectal cancer or unknown RAS mutation status (↑ mortality and tumor progression);
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Exposure to sunlight (may exacerbate dermatologic toxicity);
History of tick bites, red meat allergy, or in presence of IgE antibodies directed against galactose-α-1,3-galactose (alpha-gal) (↑ risk of anaphylaxis);
Rep: Women of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

Most adverse reactions reflect combination therapy with irinotecan

CV: CARDIOPULMONARY ARREST, peripheral edema, SUDDEN CARDIAC DEATH

Derm: acneform dermatitis, hypertrichosis, nail disorder, pruritus, skin desquamation, skin infection, STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS (TEN)

EENT: conjunctivitis, ulcerative keratitis

F and E: dehydration, hypomagnesemia

GI: abdominal pain, constipation, diarrhea, nausea, vomiting, ↓weight, anorexia, stomatitis

GU: ↓fertility (females), renal failure

Hemat: anemia, leukopenia

MS: back pain

Neuro: malaise, depression, headache, insomnia

Resp: cough, dyspnea, INTERSTITIAL LUNG DISEASE, PULMONARY EMBOLISM

Misc: fever, INFUSION REACTIONS (INCLUDING ANAPHYLAXIS)

Interactions ⬆ ⬇

Drug-drug:

None reported.

Route/Dosage ⬆ ⬇

Head and Neck Cancer with Radiation

IV (Adults ): 400 mg/m² administered 1 wk prior to initiation of radiation therapy, followed by 250 mg/m² once weekly for the duration of radiation therapy or until disease progression or unacceptable toxicity (complete infusion 1 hr prior to radiation therapy).

Head and Neck Cancer Monotherapy or in Combination with Platinum-Based Therapy and 5-Fluorouracil

IV (Adults ): Monotherapy (weekly regimen): 400 mg/m² initially, followed by 250 mg/m² once weekly until disease progression or unacceptable toxicity. Monotherapy (biweekly regimen): 500 mg/m² every 2 wk until disease progression or unacceptable toxicity. Combination therapy with platinum-based therapy and 5-fluorouracil (weekly regimen): 400 mg/m² initially, followed by 250 mg/m² once weekly until disease progression or unacceptable toxicity (complete infusion 1 hr to prior to administering platinum-based therapy with 5-fluorouracil). Combination therapy with platinum-based therapy and 5-fluorouracil (biweekly regimen): 500 mg/m² every 2 wk until disease progression or unacceptable toxicity (complete infusion 1 hr prior to administering platinum-based therapy with 5-fluorouracil).

Colorectal Cancer

IV (Adults ): Monotherapy (weekly regimen): 400 mg/m² initially, followed by 250 mg/m² once weekly until disease progression or unacceptable toxicity. Monotherapy (biweekly regimen): 500 mg/m² every 2 wk until disease progression or unacceptable toxicity. Combination therapy with irinotecan or FOLFIRI (weekly regimen): 400 mg/m² initially, followed by 250 mg/m² once weekly until disease progression or unacceptable toxicity (complete infusion 1 hr prior to administering irinotecan or FOLFIRI). Combination therapy with irinotecan or FOLFIRI (biweekly regimen): 500 mg/m² every 2 wk until disease progression or unacceptable toxicity (complete infusion 1 hr prior to administering irinotecan or FOLFIRI). Combination therapy with encorafenib: 400 mg/m² initially, followed by 250 mg/m² once weekly until disease progression or unacceptable toxicity.

Availability ⬆ ⬇

Solution for injection: 2 mg/mL

Assessment ⬆ ⬇

Assess for infusion reaction (rapid onset of airway obstruction [bronchospasm, stridor, hoarseness], urticaria, hypotension, loss of consciousness, myocardial infarction, cardiopulmonary arrest) for at least 1 hr following infusion. Longer observation periods may be required for those who experience infusion reactions. Risk of anaphylactic reactions may be increased in patients with a history of tick bites, red meat allergy, or in the presence of IgE antibodies directed against galactose-α-1,3-galactose (alpha-gal). Most reactions occur during first dose, but may also occur in later doses. For severe reactions, immediately stop infusion and discontinue cetuximab permanently. Epinephrine, corticosteroids, IV antihistamines, bronchodilators, and oxygen should be available for reactions. Mild to moderate reactions (chills, fever, dyspnea) may be managed by slowing rate of infusion and administration of antihistamines. If infusion reaction is Grade 1 or 2, reduce infusion rate by 50%. If infusion reaction is Grade 3 or 4, discontinue immediately and permanently.
Assess for acute onset or worsening of pulmonary symptoms. Delay infusion 1–2 wk; if condition improves, continue at dose that was being administered at the time of occurrence. If no improvement in 2 wk or interstitial lung disease is confirmed, discontinue cetuximab and treat appropriately.
Assess for dermatologic toxicities (acneform rash, skin drying and fissuring, inflammatory and infectious sequelae [blepharitis, cheilitis, cellulitis, cyst]). Treat symptomatically. Acneform rash usually occurs within initial 2 wk of therapy and resolves following cessation, but may continue up to 28 days following therapy. For 1st occurrence of dermatologic toxicities; Grade 3 or 4, delay infusion 1–2 wk; if improvement, continue at 250 mg/m², if no improvement, discontinue cetuximab. For 2nd occurrence; Grade 3 or 4, delay infusion 1–2 wk; if improvement, reduce dose to 200 mg/m², if no improvement, discontinue cetuximab. For 3rd occurrence; Grade 3 or 4, delay infusion 1–2 wk; if improvement, reduce dose to 150 mg/m², if no improvement, discontinue cetuximab. For 4th occurrence; Grade 3 or 4, discontinue cetuximab.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.Determine Ras mutation and EGFR-expression status using FDA-approved tests prior to initiating treatment. Only patients whose tumors are K-ras wild-type should receive cetuximab. Determine BRAF V600E mutation before use for metastatic colon cancer. Information on FDA-approved tests for the detection of K-ras or BRAF V600E mutations in patients with metastatic colorectal cancer is available at: http://www.fda.gov/CompanionDiagnostics.
Consider testing patients for alpha-gal IgE antibodies using FDA-cleared methods before starting therapy. Negative results for alpha-gal antibodies do not rule out the risk of severe infusion reactions.
May cause anemia and leukopenia.
- Monitor serum electrolytes, especially serum magnesium, potassium, and calcium, closely during and periodically for at least 8 wk following infusion. May cause hypomagnesemia, hypocalcemia, and hypokalemia; may occur from days to mo after initiation of therapy. May require electrolyte replacement. May lead to cardiopulmonary arrest and sudden death.

Implementation ⬆ ⬇

Premedicate with histamine₁ antagonist (diphenhydramine 50 mg) 30–60 min prior to first dose; base subsequent administration on presence and severity of infusion reactions.

IV Administration:

Administer through a low protein binding 0.22-micrometer in-line filter placed as proximal to patient as possible. Solution should be clear and colorless and may contain a small amount of white amorphous cetuximab particles. Do not shake or dilute.
- Can be administered via infusion pump or syringe pump. Cetuximab should be piggybacked to the patient's infusion line.
- Observe patient for 1 hr following infusion.
Intermittent Infusion: For administration via infusion pump: Draw up volume of a vial using vented spike needle or other transfer device. Transfer to a sterile evacuated container or bag. Repeat with new needle for each vial until calculated volume is in container. Affix infusion line and prime with cetuximab before starting infusion.
- For administration via syringe pump: Draw up volume of a vial using sterile syringe attached to an appropriate vented spike needle. Place syringe into syringe driver of a syringe pump and set rate. Connect infusion line and prime with cetuximab. Use a new needle and filter for each vial. Diluent: Do not dilute.Concentration: 2 mg/mL.
Rate: Administer over 2 hr at a rate not to exceed 10 mg/min. Use 0.9% NaCl to flush line at end of infusion.
- Cetuximab infusion must be completed 1 hr prior to FOLFIRI (irinotecan, 5-fluorouracil, leucovorin) regimen. May infuse subsequent weekly infusions over 1 hr.

Patient/Family Teaching ⬆ ⬇

Explain purpose of cetuximab and potential side effects to patient.
Advise patient to notify health care professional promptly if dermatologic changes (itchy, dry, scaly, or cracking skin, and inflammation, infection or swelling at base of nails or loss of the nails), conjunctivitis, blepharitis, or decreased vision, and signs and symptoms of pulmonary toxicity (new or worsening cough, chest pain, shortness of breath), infusion reactions (fever, chills, or breathing problems) promptly. Risk for infusion reactions in patients who have had a tick bite or red meat allergy.
Caution patient to wear sunscreen and hats and limit sun exposure during therapy and for 2 mo following last dose of cetuximab.
Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception during and for 2 mo after last dose of therapy and to avoid breastfeeding during and for 2 mo following therapy. May impair female fertility.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇