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Pharmacologic class: Epidermal growth factor receptor (EGFR) inhibitor
Therapeutic class: Antineoplastic
Pregnancy risk category C
FDA Box Warning
• Drug may cause severe infusion reactions. If severe reaction occurs, stop infusion immediately and discontinue therapy permanently.
• Cardiopulmonary arrest, sudden death, or both occurred in 2% of patients with squamous-cell carcinoma of head and neck who received drug plus radiation therapy and in 3% of patients with squamous-cell carcinoma of head and neck treated with European-approved cetuximab in combination with platinum-based therapy with 5-fluorouracil. Monitor serum electrolyte levels closely during and after therapy.
Binds to EGFR, competitively inhibiting binding of epidermal growth factor and other ligands and blocking phosphorylation and activation of receptor-associated kinases. These actions lead to cell growth inhibition, apoptosis induction, and decreased matrix metalloproteinases and vascular endothelial growth factor.
Solution for injection: 50-ml single-use vial containing 100 mg (2 mg/ml), 100-ml single-use vial containing 200 mg (2 mg/ml)
Indications and dosages
➣ EGFR-expressing metastatic colorectal carcinoma, used alone in patients intolerant to irinotecan-based chemotherapy or in combination with irinotecan in patients refractory to irinotecan-based therapy
Adults: 400 mg/m2 initial loading dose given as 120-minute I.V. infusion followed by maintenance dose of 250 mg/m2 infused I.V. over 60 minutes
➣ Locally or regionally advanced squamous-cell carcinoma of head and neck, in combination with radiation therapy
Adults: 400 mg/m2 as initial loading dose (first infusion) given as 120-minute I.V. infusion 1 week before initiation of radiation therapy. For recommended weekly maintenance dose (all other infusions), 250 mg/m2 infused I.V. over 60 minutes weekly for duration of radiation therapy (6 to 7 weeks) given 1 hour before radiation therapy.
➣ Locally or regionally advanced squamous-cell carcinoma of head and neck in combination with platinum-based therapy plus 5-fluorouracil (5-FU)
Adults: Initially, 400 mg/m2 on day of initiation of platinum-based therapy with 5-FU as a 120-minute I.V. infusion. Complete cetuximab administration 1 hour before platinum-based therapy with 5-FU. For recommended subsequent weekly doses (all other infusions), 250 mg/m2 I.V. infusion over 60 minutes for duration of radiation therapy (6 to 7 weeks) or until disease progression or unacceptable toxicity occurs.
➣ Recurrent or metastatic squamous-cell carcinoma of head and neck (used alone) in patients for whom platinum-based therapy has failed
Adults: Initially, 400-mg/m2 I.V. infusion followed by 250 mg/m2 I.V. weekly until disease progresses or unacceptable toxicity occurs
• Cancers that overexpress EGFR
• Mild to moderate infusion (Grade 1 or 2) reaction
• Severe acneiform rash
• Acute onset or worsening of pulmonary symptoms
Use cautiously in:
• hypersensitivity to murine proteins or drug components
• dermatologic or pulmonary toxicities
• patients receiving concurrent radiation therapy and cisplatin
• patients receiving concurrent radiation therapy who have history of coronary artery disease, arrhythmias, and congestive heart failure
• pregnant or breastfeeding patients
• children (safety and efficacy not established).
• As ordered, premedicate with histamine1-antagonist (such as 50 mg diphenhydramine I.V.).
• Use low-protein-binding, 0.22 micrometer in-line filter placed as close to patient as possible.
☞ Don't give by I.V. push or bolus.
☞ Don't shake or dilute vial.
• Administer by I.V. infusion pump or syringe pump.
• Piggyback drug to patient's infusion line.
• Give initial dose over 2 hours at a rate of 10 mg/minute; give subsequent weekly doses over 1 hour. Maximum infusion rate shouldn't exceed 10 mg/minute.
• At end of infusion, flush I.V. lines with normal saline solution.
☞ Be aware that 90% of infusion reactions occur with first infusion. Observe patient closely for 1 hour after infusion (or longer in patients who have experienced infusion reactions). Severe and life-threatening infusion reactions have occurred, including rapid-onset airway obstruction (bronchospasm, stridor, hoarseness), urticaria, and hypotension.
☞ Permanently reduce infusion rate by 50% if patient experiences mild or moderate infusion reaction. Immediately and permanently discontinue drug in patient who experiences severe (Grade 3 or 4) infusion reaction.
• Make sure appropriate medical resources for treatment of severe infusion reactions are available during infusion.
• Expect patients with colorectal cancer to undergo immunohistochemical testing for EGFR expression using DakoCytomation EGFR pharmDx test kit.
• Interrupt therapy if patient develops acute onset or worsening of pulmonary symptoms. Discontinue therapy if pneumonitis or lung infiltrates are confirmed.
• For first occurrence of severe acneiform rash, delay infusion 1 to 2 weeks; if condition improves, continue therapy at 250 mg/m2; if no improvement occurs, withdraw drug. For second occurrence, delay infusion 1 to 2 weeks; if condition improves, reduce dosage to 200 mg/m2; if no improvement occurs, withdraw drug. For third occurrence, delay infusion for 1 to 2 weeks; if condition improves, reduce dosage to 150 mg/m2; if no improvement occurs, withdraw drug. On fourth occurrence, withdraw drug.
CNS: headache, insomnia, depression, malaise, asthenia
CV: cardiopulmonary arrest
GI: abdominal pain, diarrhea, nausea, vomiting, constipation, stomatitis, dyspepsia, anorexia
GU: renal failure
Hematologic: leukopenia, anemia
Metabolic: dehydration, electrolyte abnormalities
Musculoskeletal: back pain
Respiratory: dyspnea, increased cough, interstitial lung disease, pulmonary embolus
Skin: acneiform rash, alopecia, skin disorder, nail disorder, pruritus
Other: weight loss, fever, pain, infection, peripheral edema, severe infusion reaction
Drug-diagnostic tests. Calcium, magnesium: decreased
Drug-behaviors. Sun exposure: exacerbated skin reactions
• Watch for signs and symptoms of infusion reaction.
• Monitor patient for hypomagnesemia and hypocalcemia during therapy and for 8 weeks afterward.
• Closely monitor serum electrolytes (including serum magnesium, potassium, and calcium) during therapy and after combination drug and radiation therapy in patients with history of coronary artery disease, arrhythmias, and heart failure.
• Monitor patient with dermatologic toxicities for inflammatory or infectious sequelae.
• Watch for pulmonary toxicities in patient with history of interstitial pneumonitis or pulmonary fibrosis. Be prepared to interrupt or discontinue therapy and intervene appropriately.
• Monitor for potentially serious cardiotoxicity if patient is receiving drug in combination with radiation therapy and cisplatin.
• Stay alert for severe diarrhea and electrolyte depletion.
☞ Urge patient to immediately report rash, which may indicate skin toxicity.
☞ Instruct patient to immediately report new or worsening respiratory or cardiovascular symptoms.
• Advise patient to use sunscreen and wear a hat when outdoors and to limit sun exposure, because sunlight can exacerbate skin reactions.
• Caution female with childbearing potential that drug may cause pregnancy loss or pose hazard to fetus.
• Advise female to discontinue breastfeeding during therapy and for 60 days after last dose.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the tests and behaviors mentioned above.
Pharmacologic: monoclonal antibodies
Adverse Reactions/Side EffectsMost adverse reactions reflect combination therapy with irinotecan
Central nervous system
- malaise (most frequent)
Ear, Eye, Nose, Throat
- ulcerative keratitis
- interstitial lung disease
- cardiopulmonary arrest (life-threatening)
- pulmonary embolism (life-threatening)
- sudden cardiac death (life-threatening)
- abdominal pain (most frequent)
- constipation (most frequent)
- diarrhea (most frequent)
- nausea (most frequent)
- vomiting (most frequent)
- renal failure
- acneform dermatitis (most frequent)
- nail disorder
- skin desquamation
- skin infection
Fluid and Electrolyte
- peripheral edema
- back pain
- weight loss
- infusion reactions (life-threatening)
- fever (most frequent)
- desquamation of mucosal epithelium
Drug-Drug interactionNone noted.
Head & Neck Cancer with Radiation or in Combination with Platinum-Based Therapy with 5-Fluorouracil
Head and Neck Cancer Monotherapy
- 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. 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.
- Assess for onset or worsening of pulmonary symptoms. Interrupt therapy to determine nature of symptoms. If 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.
- Lab Test Considerations: genetic implication Determine K-Ras mutation and EGFR-expression status using FDA-approved tests prior to initiating treatment. Only patients whose tumors are K-Ras mutationnegative (wild-type) should receive cetuximab.
- Lab Test Considerations: 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 months after initiation of therapy. May require electrolyte replacement. May lead to cardiopulmonary arrest and sudden death.
Potential Nursing DiagnosesIneffective breathing pattern (Adverse Reactions)
Impaired skin integrity (Adverse Reactions)
- Premedicate with histamine1 antagonist (diphenhydramine 50 mg) 30–60 min prior to first dose; base subsequent administration on presence and severity of infusion reactions.
- 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.
- pH: 7.0–7.4.
- 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-fluoruracil, leucovorin) regimen. May infuse subsequent weekly infusions over 1 hr.
- Explain purpose of cetuximab and potential side effects to patient.
- Advise patient to report dermatologic changes and signs and symptoms of infusion reactions (fever, chills, or breathing problems) promptly.
- Caution patient to wear sunscreen and hats and limit sun exposure during therapy during and for 2 mo following last dose of cetuximab.
- Advise both female and male patients to use adequate contraception during and for 6 mo following therapy and to avoid breast feeding during and for 2 mo following therapy.
- Decreased tumor growth and spread.