Cetuximab is a chimeric monoclonal antibody that inhibits the binding of epidermal growth factor to tumor cells, thus inhibiting the growth and promote the process of apoptosis. It is used to treat the following conditions:

• For the treatment of KRAS wild-type, epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer

  • In combination with FOLFIRI [irinotecan, fluorouracil, and leucovorin as first-line treatment.
  • In combination with irinotecan in patients refractory to irinotecan-based chemotherapy,
  • As monotherapy in patients who have failed irinotecan and oxaliplatin-based chemotherapy or who are intolerant to irinotecan.

(Cetuximab is not indicated for the treatment of RAS-mutant colorectal cancer or when RAS mutation test result is unknown)

• For the treatment of squamous cell cancer of the head and neck

  • as monotherapy for the recurrent or metastatic disease after platinum-based chemotherapy failure
  • in combination with radiation therapy of locally or regionally advanced disease
  • in combination with platinum and fluorouracil-based chemotherapy as first-line treatment of locoregional or metastatic disease.

• Off-Label Uses of Cetuximab in Adults include:

  • Advanced or metastatic Penile cancer (squamous cell carcinoma)
  • Unresectable Squamous cell skin cancer.

Cetuximab Dose in Adults

Note: Premedicate with an H-2 antagonist like diphenhydramine intravenously 30 - 60 minutes before the first dose.

• Metastatic colorectal cancer (KRAS wild-type - without mutation):

  • Initial loading dose:
    • 400 mg/m² infused over 2 hours
  • Maintenance dose:
    • 250 mg/m² infused over one hour once a week until disease progression or unacceptable toxicity

Note: Complete cetuximab infusion one hour before irinotecan or FOLFIRI when given in combination.

• Off-label dosing of Cetuximab as twice a week administration in advanced Colorectal cancer:

  • 500 mg/m² intravenous every two weeks in combination with irinotecan.

• Use of Cetuximab in the treatment of squamous cell carcinoma of the Head and neck:

  • Initial loading dose:
    • 400 mg/m² infused over two hours.
  • Maintenance dose:
    • 250 mg/m² infused over one hour weekly

Note:

• The loading dose should be administered one week before the radiation (when given in combination with radiotherapy) and the maintenance dose should be completed one hour before.
• When given in combination with chemotherapy, the loading dose should be administered on the day of initiation of platinum and fluorouracil-based chemotherapy and completed one hour before the initiation of chemotherapy.

• Off-label use of Cetuximab in the treatment of advanced or metastatic squamous cell Penile cancer:

  • Initial loading dose:
    • 400 mg/m² intravenous
  • Maintenance dose:
    • 250 mg/m² once a week

• Off-label use of Cetuximab in treatment of unresectable Squamous cell skin cancer:

  • Initial loading dose:
    • 400 mg/m²
  • Maintenance dose:
    • 250  mg/m² once a week until disease progression.

Cetuximab Dose in Childrens

Not applicable

Pregnancy Risk Factor: C

• Although cetuximab was not tested in pregnant women, the manufacturer suggests effective contraception for women of childbearing years during therapy and the two weeks after the last dose.

Use of Cetuximab while breastfeeding

• It is not advised to breastfeed during therapy or for at least two months after the last dose.

Cetuximab Dose in Renal Disease:

The manufacturer has not recommended any dose adjustment in patients with renal impairment.

Cetuximab Dose in Liver Disease:

The manufacturer has not recommended any dose adjustment in patients with liver disease.

Common Side Effects of Cetuximab include:

• Cardiovascular:
  • Cardiac disorder
• Central nervous system:
  • Fatigue
  • Malaise
  • Pain
  • Peripheral sensory neuropathy
  • Headache
  • Insomnia
  • Confusion
  • Chills
  • Rigors
  • Anxiety
  • Depression
• Dermatologic:
  • Desquamation
  • Acneiform eruption
  • Radiodermatitis
  • Xeroderma
  • Pruritus
  • Skin rash
  • Changes in nails
  • Acne vulgaris
  • Paronychia
  • Palmar-plantar erythrodysesthesia
  • Skin fissure
  • Alopecia
• Endocrine & metabolic:
  • Weight loss
  • Hypomagnesemia
  • Dehydration
  • Hypocalcemia
  • Hypokalemia
• Gastrointestinal:
  • Diarrhea
  • Nausea
  • Abdominal pain
  • Constipation
  • Vomiting
  • Stomatitis
  • Anorexia
  • Dyspepsia
  • Xerostomia
• Hematologic & oncologic:
  • Neutropenia
  • Leukopenia
• Hepatic:
  • Increased serum alanine aminotransferase
  • Increased serum aspartate aminotransferase
  • Increased serum alkaline phosphatase
• Infection:
  • Infection
  • Infection without neutropenia
• Local:
  • Application site reaction
• Neuromuscular & skeletal:
  • Asthenia
  • Ostealgia
  • Arthralgia
• Ophthalmic:
  • Conjunctivitis
• Respiratory:
  • Dyspnea
  • Cough
  • Pharyngitis
• Miscellaneous:
  • Fever
  • Infusion-related reaction

Less Common Side Effects of Cetuximab include:

• Cardiovascular:
  • Ischemic heart disease
• Gastrointestinal:
  • Dysgeusia
• Immunologic:
  • Antibody development
• Infection:
  • Sepsis
• Renal:
  • Renal failure syndrome

Frequency not defined:

• Dermatologic:
  • Hypertrichosis
• Endocrine & metabolic:
  • Electrolyte disorder

Contraindications to Cetuximab:

• Allergy to any drug or component of the formulation

Warnings and Precautions

• Cardiopulmonary arrest [US Boxed Warning]
  • Sudden cardiac death and cardiopulmonary arrest have been reported in patients suffering from squamous cell carcinoma of their head and neck.
  • During and after cetaximab administration, serum electrolytes including serum magnesium, serum calcium, and serum potassium should be closely monitored.
  • Patients who have had heart disease, arrhythmias, or coronary artery disease should be cautious about taking the drug. There have been several deaths.

• Dermatologic toxicities:
  • Acneiform rash may become severe enough to require discontinuation of therapy.
  • Colorectal cancer patients who have an acneiform rash have had a longer survival rate and better treatment outcomes.
  • It has been linked to life-threatening and fatal bullous mucocutaneous diseases with blisters, erosions and skin sloughing, including stevenjohnson and TEN syndromes.
  • Photosensitive reactions, as well as other skin toxicities such dryness, fissures and hypertrichosis, may be caused by photosensitive reactions. Ocular toxicities may include conjunctivitis and keratitis as well as blepharitis and keratitis.

• An abnormality in the electrolyte:
  • As electrolyte fluctuations have been reported, serum magnesium, calcium, potassium, and blood sugar should be closely monitored throughout therapy and at least eight weeks after it ends.

• Infusion reactions [US Boxed Warning]
  • Cetuximab injections have been linked to life-threatening reactions.
  • Patients may experience bronchospasm or stridor, hoarseness or hypotension, loss consciousness, shock, Myocardial Infarction and cardiac arrest.
  • Anaphylactic reactions are more common in patients who have had tick bites or allergies to red meat.
  • The majority of reactions, including up to 90%, occur after the first infusion of antihistamines despite being given prophylactics.
  • After infusion, patients should be closely monitored for at most one hour.
  • Mild reactions can be managed by slowing down the infusion rate.

• Toxicity in the lungs:
  • It is important to monitor patients for symptoms and signs of pulmonary toxicities.
  • Patients who experience acute onset or interstitial lung disease or have pulmonary symptoms should not be treated.

• Status of RAS mutation and colorectal cancer:
  • Cetuximab should only be used in patients with metastatic colorectal carcinoma that is EGFR-expressing and has not been affected by RAS mutations (KRAS, NRAS).
  • Before you start treatment, make sure to determine your RAS mutation status (using an approved test).
  • Cetuximab should not be given to patients with a mutation in codon 12 or 13 (exon 2), codon 59 or 61 (exon 3) and codon 117 (exon 4) RAS.
  • It is ineffective for patients with BRAF V600E mutation.

How to monitor?

• KRAS genotyping for cancerous tissue in patients suffering from colorectal carcinoma
• Monitor serum magnesium, serum calcium and serum potassium for at least eight weeks following treatment.
• Before starting treatment for females with reproductive potential, it is important to have a pregnancy test.
• Observe vital signs throughout infusion. Also, be sure to keep an eye on the patient for at least an hour afterward.
• Be on the lookout for signs and symptoms such as skin reactions and toxicity, including pulmonary toxicities.

How to administer Cetuximab?

• It is administered intravenously.
• The loading dose is administered over two hours, and the weekly maintenance dose takes one hour.
• Avoid intravenous push administration. 
• Do not dilute or shake the solution and use an infusion pump to administer it.
• Premedicate the patient with an H2 blocker.
• The patient should remain awake for at least one hour following infusion.
• Maximum infusion rate should not exceed 10mg/minute.
• The medication should be administered via a 0.22-micrometer in-line filter that is low in protein binding.

Mechanism of action of Cetuximab:

• Cetuximab, a chimeric monoclonal human/mouse recombinant antibody that binds and inhibits epidermal growth factors (EGF), HER1, c–ErbB-1 and other ligands, is a recombinant human/mouse chimeric monoclonal anti-biological antibody.
• Cetuximab binding to the EGFR inhibits the phosphorylation or activation receptor-associated kinases.
• This causes apoptosis and inhibits cell growth. It also decreases matrix metalloproteinase production and vascular endothelial factor production.
• Transduction of EGFR signals results in activation RAS.
• EGFR inhibition appears to not affect cells with RAS mutations.

It has a half life eliminationapproximately 112 hours (ranging between 63 and 230 hours).

Cituximab International Brands:

• Cetuxim
• Erbituks
• Erbitux

Cituximab Brands in Pakistan: