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 (women), renal failure

Hemat: anemia, leukopenia

MS: back pain

Neuro: malaise, depression, headache, insomnia

Resp: cough, dyspnea, INTERSTITIAL LUNG DISEASE (ILD), 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 reactions (bronchospasm, stridor, hoarseness, urticaria, hypotension, loss of consciousness, MI, cardiopulmonary arrest) for ≥1 hr following infusion. ↑ risk of anaphylaxis in patients with a history of tick bites or red meat allergy or the presence of IgE antibodies against galactose-α-1, 3-galactose (alpha-gal). Most reactions occur during 1st dose, but may occur later. For Grade 1 or 2 infusion reactions,↓ infusion rate by 50%. For Grade 3 or 4 infusion reactions, immediately discontinue cetuximab. Keep epinephrine, corticosteroid, antihistamine, bronchodilator, and oxygen nearby during infusion.
Assess for pulmonary toxicity. If acute onset or worsening of symptoms occur, delay infusion 1–2 wk; when resolved, continue at previous dose. If no improvement in 2 wk or ILD confirmed, permanently discontinue cetuximab.
Assess for dermatologic toxicity (acneform rash, inflammation, infection). Treat symptomatically. Acneform rash usually occurs in initial 2 wk of therapy and may continue up to 28 days following therapy. If 1st occurrence of Grade 3 or 4 dermatologic toxicities, delay infusion 1–2 wk; when improved, continue at 250 mg/m². If 2nd occurrence of Grade 3 or 4 dermatologic toxicities, delay infusion 1–2 wk; when improved, ↓ dose to 200 mg/m². If 3rd occurrence of Grade 3 or 4 dermatologic toxicities, delay infusion 1–2 wk; when improved, ↓ dose to 150 mg/m². If 4th occurrence of Grade 3 or 4 dermatologic toxicities or no improvement at any occurrence, permanently discontinue cetuximab.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy. Determine RAS mutation and EGFR-expression status using FDA-approved tests before 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 for metastatic colorectal cancer is available at http://www.fda.gov/CompanionDiagnostics.
Consider testing patients for alpha-gal IgE antibodies using FDA-cleared method 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 magnesium, potassium, and calcium, during and periodically for ≥8 wk following infusion. May cause hypomagnesemia, hypocalcemia, and hypokalemia; may occur from days to months after initiation of therapy. 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 reaction.

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 particles. Do not shake.
- Can be administered via infusion pump or syringe pump. Piggyback cetuximab into infusion line.
- Observe patient for 1 hr following infusion.
Intermittent Infusion: For administration via infusion pump: Remove cetuximab from vial(s) using vented spike needle. Transfer to sterile evacuated container or bag. Repeat with new needle for each vial. Affix infusion line and prime with cetuximab before starting infusion.
- For administration via syringe pump: Remove cetuximab from vial(s) using vented spike needle. Place syringe into driver of a syringe pump and set rate. Connect infusion line and prime with cetuximab. Use a new needle and filter for each vial. Concentration: 2 mg/mL.
Rate: Infuse 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 of dermatologic changes (itchy, dry, scaly, or cracking skin; inflammation, infection, or swelling at base of nails; loss of nails), conjunctivitis, blepharitis, ↓ vision, and signs and symptoms of pulmonary toxicity (new or worsening cough, chest pain, shortness of breath) or infusion reactions (fever, chills, breathing problems). ↑ 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 women of reproductive potential to use effective contraception during therapy and for 2 mo after last dose and to avoid breastfeeding during therapy and for 2 mo after last dose. May impair female fertility.

Evaluation/Desired Outcomes ⬆ ⬇

Decreased tumor growth and spread.

US Brand Names ⬆ ⬇

Code ⬆

NDC Code

66733- ImClone LLC
- 66733-948- ERBITUX
  - 66733-948-23- 1 VIAL, SINGLE-DOSE in 1 CARTON (66733-948-23) / 50 mL in 1 VIAL, SINGLE-DOSE

66733- ImClone LLC
- 66733-958- ERBITUX
  - 66733-958-23- 1 VIAL, SINGLE-DOSE in 1 CARTON (66733-958-23) / 100 mL in 1 VIAL, SINGLE-DOSE

73424- ImClone Systems LLC
- 73424-0561-
  - 73424-0561-1- 1 BAG in 1 TANK (73424-0561-1) / 102 kg in 1 BAG

73424- ImClone Systems LLC
- 73424-0561-
  - 73424-0561-2- 1 BAG in 1 TANK (73424-0561-2) / 204 kg in 1 BAG

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇