Cetuximab

Pronunciation: (se-TUX-i-mab)
Class: Antineoplastic, Monoclonal antibody

Trade Names

Erbitux
- Injection, solution 2 mg/mL

Pharmacology

Competitively inhibits binding of epidermal growth factor (EGF) to receptors, which blocks phosphorylation and activation of receptor-associated kinases, resulting in inhibition of cell growth.

Pharmacokinetics

Absorption

Steady-state peak and trough values range from 168 to 235 mcg/mL and 41 to 85 mcg/mL, respectively.

Distribution

Vd is approximately 2 to 3 L/m ² .

Elimination

Mean t _½ is about 112 h.

Special Populations

Gender

Women with colorectal cancer have a 25% lower intrinsic Cl than men; however, no changes in dosing are needed.

Indications and Usage

In combination with radiation therapy for the treatment of locally or regionally advanced squamous cell carcinoma of the head and neck; as single-agent treatment of recurrent or metastatic squamous cell carcinoma of the head and neck in patients in whom prior platinum-based therapy failed; in combination with irinotecan for the treatment of epidermal growth factor receptor (EGFR)–expressing metastatic colorectal carcinoma in patients who are refractory to irinotecan-based chemotherapy; as single-agent treatment of EGFR–expressing metastatic colorectal cancer after failure of both irinotecan- and oxaliplatin-based regimens and in patients who are intolerant to irinotecan-based regimens.

Contraindications

Standard considerations.

Dosage and Administration

Colorectal Cancer
Adults

IV 400 mg/m ² as an initial loading dose administered as a 120-min infusion (max rate of infusion, 10 mg/min). The weekly maintenance dose is 250 mg/m ² infused over 60 min (max rate of infusion, 10 mg/min) until disease progression or unacceptable toxicity.

Squamous Cell Carcinoma of the Head and Neck
Adults

IV In combination with radiation therapy, the recommended dose is 400 mg/m ² as a loading dose given as a 120-min infusion (max infusion rate, 10 mg/min) 1 wk prior to initiation of a course of radiation therapy. The recommended weekly maintenance dose is 250 mg/m ² infused over 60 min (max infusion rate, 10 mg/min) weekly for the duration of radiation therapy (6 to 7 wk). Complete administration 1 h prior to radiation therapy. As a single agent, the recommended initial dose is 400 mg/m ² followed by 250 mg/m ² weekly (max infusion rate, 10 mg/min) until disease progression or unacceptable toxicity.

Dose Modification
Adults Dermatologic toxicity

IV If patient experiences severe acneform rash: At first occurrence, delay infusion 1 to 2 wk and, if improvement occurs, continue at 250 mg/m ² . Discontinue if no improvement. At second occurrence, delay infusion 1 to 2 wk and, if improvement occurs, reduce dose to 200 mg/m ² . Discontinue if no improvement. At third occurrence, delay infusion 1 to 2 wk and, if improvement occurs, reduce dose to 150 mg/m ² . Discontinue if no improvement. At fourth occurrence, discontinue.

Infusion reactions

IV Reduce the infusion rate by 50% in patients experiencing mild or moderate (grade 1 or 2) or nonserious (grade 3 or 4) infusion reactions; permanently discontinue in patients experiencing severe (grade 3 or 4) infusion reactions.

General Advice

Follow institutional procedures for handling, administrating, and disposing of anticancer drugs.
Premedicate patient with antihistamine (eg, diphenhydramine IV) 30 to 60 min prior to first dose.
Do not shake or dilute.
Do not mix with any other medications.
Do not administer if cloudy or discolored. A small amount of white amorphous particulates is normal.
Administer prescribed dose using syringe pump or infusion pump following manufacturer's recommendations.
Administer with use of low protein binding 0.22 mcm in-line filter placed as proximal to the patient as possible.
Discard unused portion of vial. Do not save any unused portion for future use.

Storage/Stability

Store unopened vials in refrigerator (36° to 46°F). Do not freeze. Preparations of cetuximab in infusion containers are stable for up to 8 h at controlled room temperature (68° to 77°F) or 12 h if refrigerated (36° to 46°F). Discard any remaining solution in infusion container after 8 h at controlled room temperature or after 12 h if refrigerated.

Drug Interactions

None well documented.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Adverse reaction percentages are for grades 1 to 4 toxicity with cetuximab monotherapy.

CNS

Fatigue (89%); headache (33%); insomnia (30%); confusion (15%); anxiety (14%); depression (13%).

Dermatologic

Rash/desquamation (89%); dry skin (49%); pruritus (40%); nail changes (21%).

Electrolytes

Hypomagnesemia (55%).

GI

Abdominal pain (59%); constipation (46%); diarrhea (39%); vomiting (37%); stomatitis (25%); dry mouth (11%).

Musculoskeletal

Bone pain (15%).

Respiratory

Dyspnea (48%); cough (29%).

Miscellaneous

Infection without neutropenia (35%); fever (30%); infusion reactions (20%); chills/rigors (13%).

Precautions

Warnings

Cardiopulmonary arrest

Cardiopulmonary arrest and/or sudden death occurred in 2% of patients with squamous cell carcinoma of the head and neck treated with cetuximab plus radiation therapy. Fatal reactions occurred within 1 to 43 days after the last cetuximab treatment.

Infusion reactions

Serious infusion reactions occurred in approximately 3% of patients in clinical trials, with fatal outcomes reported in fewer than 1 in 1,000. Immediately interrupt and permanently discontinue infusion for serious infusion reactions.

Monitor

Cardiopulmonary arrest

Closely monitor serum electrolytes, including serum calcium, magnesium, and potassium, during and after cetuximab therapy.

Infusion reaction

Closely monitor patient during and for 1 h following each infusion for signs and symptoms of infusion reaction (eg, bronchospasm, hives, hoarseness, hypotension, stridor). If noted and severe, immediately discontinue infusion and be prepared to treat appropriately (eg, bronchodilators, corticosteroids, epinephrine, IV antihistamines, oxygen).

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

No difference in safety and efficacy observed in patients 65 yr of age and older compared with younger patients.

Hypersensitivity

Use with caution in patients who are hypersensitive to cetuximab, murine proteins, or any component of this product.

Combination therapy

Safety of cetuximab in combination with radiation therapy and cisplatin has not been established.

Dermatologic toxicity

Reactions, including acneform rash, inflammatory and infectious sequelae, and skin drying and fissuring, may occur. Monitor patient for dermatological toxicity (eg, acneform rash, infection, inflammation, skin drying and fissuring). Be prepared to treat infectious sequelae with topical and/or oral antibiotics.

Electrolyte abnormalities

The onset of hypomagnesemia and accompanying electrolyte abnormalities occurred days to months after initiation of cetuximab. Periodically monitor for hypomagnesemia, hypocalcemia, and hypokalemia during and for at least 8 weeks following the completion of cetuximab.

IV antihistamine

Ensure that premedication with IV antihistamine (eg, diphenhydramine) has been ordered for each infusion.

Pulmonary toxicity

Interstitial lung disease has been reported. Monitor patient for signs and symptoms of interstitial lung disease (eg, acute onset or worsening of pulmonary symptoms). Interrupt therapy if noted.

Sun exposure

Because sunlight can exacerbate any skin reactions, instruct patients to use sunscreen, wear hats, and limit sun exposure.

Overdosage

Symptoms

No data available.

Patient Information

Advise patient, family, or caregiver that medication will be prepared and administered by health care provider in a health care setting.
Review dosing schedule with patient, family, or caregiver.
Advise patient, family, or caregiver to immediately report any of the following to health care provider: acne-like rash, appetite loss, diarrhea, fever, inflammation or infection, persistent nausea, persistent or worsening general body weakness or fatigue, skin drying or splitting, sores in mouth, unexplained shortness of breath or difficulty breathing, vomiting.
Advise patient to avoid unnecessary exposure to sunlight or tanning lamps and to use sunscreen and wear protective clothing to reduce risk of worsening any skin reactions.
Caution women of childbearing potential to avoid becoming pregnant during therapy.