Dosing & Uses
Dosage Forms & Strengths
- Indicated for treatment of KRAS mutation-negative (wild-type), epidermal growth factor receptor (EGFR)-expressing, metastatic colorectal cancer as determine by FDA-approved tests (eg, therascreen KRAS RGQ PCR Kit) for this use
- Determine EGFR-expression status using FDA-approved tests prior to initiating treatment; also confirm absence of a Ras mutation prior to initiation of treatment
- 1) In combination with FOLFIRI (irinotecan, 5-fluorouracil, leucovorin) for first-line treatment,
- 2) In combination with irinotecan in patients who are refractory to irinotecan-based chemotherapy, and
- 3) As a single agent in patients who have failed oxaliplatin- and irinotecan-based chemotherapy or who are intolerant to irinotecan
- Dosage is for either monotherapy or in combination
- Loading Initial dose: 400 mg/m² IV infused over 2 hr
- Maintenance: 250 mg/m² IV infusion over 60 min qWeek until disease progression or unacceptable toxicity
- Complete cetuximab administration 1 hr prior to FOLFIRI
- Not to exceed infusion rate of 10 mg/min
Limiation of use
- Not indicated for the treatment of patients with colorectal cancer that harbor somatic mutations in exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146) of either K-Ras or N-Ras (referred to as Ras) or when he results of the Ras mutation tests are unknown
Head & Neck Cancer
- Indicated for initial treatment of locally or regionally advanced squamous cell carcinoma of head/neck with radiation therapy
- Monotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck progressing after platinum-based therapy
- Combined with platinum-based therapy with 5-FU for metastatic head and neck cancer
Subsequent doses: 250 mg/m²/week; infuse over 60 minutes (not to exceed 10 mg/min)
With radiation: Initiate 1 week prior to beginning radiation therapy, continue qWeek x 6-7 weeks
With platinum-based therapy with 5-FU: Initiate on the day beginning chemotherapy; complete cetuximab infusion 1 hr prior to administering platinum-based therapy with 5-FU
Monotherapy or with chemotherapy: Administer qWeek until disease progression or unacceptable toxicity
Premedicate with an H1 antagonist (eg, 50 mg of diphenhydramine IV)
Infuse initial dose over at least 2 hr
Infuse subsequent doses over at least 60 minutes (not to exceed 10 mg/min)
- Mild-moderate (grade I/II) infusion reaction: Infusion rate permanently reduced by 50%
- Severe (grade III/IV) infusion reaction: Immediately and permanently discontinued
Monitor: Electrolytes (for hypomagnesemia, hypocalcemia, hypokalemia)
Safety and efficacy not established
Acneform rash (90%)
Abdominal pain (25%)
Infusion reaction (25%)
Nail disorder (16%)
Back pain (11%)
Cough increased (10%)
Peripheral edema (10%)
Weight loss (9%)
Skin disorder (5%)
Frequency Not Defined
Toxic epidermal necrolysis
Life-threatening and fatal bullous mucocutaneous disease
Black Box Warnings
Severe infusion reactions occurred with this agent in approximately in 3% of patients in clinical trials, with fatal outcome reported in less than 1 in 1000. Immediately interrupt and permanently discontinue cetuximab infusion for serious infusion reactions
Cardiopulmonary arrest and/or sudden death occurred in 2% (4/208) of patients with squamous cell carcinoma of the head and neck treated with radiation therapy and cetuximab. Closely monitor serum electrolytes, including serum magnesium, potassium, and calcium, during and after cetuximab therapy
Hypersensitivity (history of serious infusion reaction)
Use in colorectal cancer only with confirmed KRAS mutation negative (wild-type)
Risk of cardiopulmonary arrest and sudden death
Increases risk of electrolyte depletion, especially hypomagnesemia; periodically monitor during and for at least 8 wk following completion of therapy; replete electrolytes as necessary
Risk of infusion reactions; monitor patients following infusion; discontinue therapy for serious infusion reactions (see dose modifications)
Mucocutaneous adverse reactions may occur; limit sun exposure; wear sunscreen and hats
Dermatologic toxicities include life-threatening and fatal bullous mucocutaneous disease with blisters, erosions, skin sloughing, acneiform rash, skin drying and fissuring, paronychial inflammation, infectious sequelae (eg, Streptococcal aureus sepsis, abscess formation, cellulitis, blepharitis, conjunctivitis, keratitis/ulcerative keratitis with decreased visual acuity, cheilitis), and hypertrichosis; monitor for inflammatory or infectious sequelae
Increased incidence of grade 3-4 mucositis, radiation recall syndrome, acneiform rash, cardiac events, and electrolyte disturbances when used in combination with radiation and cisplatin; coadministration did not improve progression-free survival
Interstitial lung disease reported; interrupt treatment for acute onset or worsen of pulmonary symptoms
Increased tumor progression, increased mortality, or lack of benefit in patients with Ras-mutant metastatic colorectal cancer (mCRC)
Advise females of reproductive potential to use effective contraception during treatment with and for 6 months after the last dose
Pregnancy & Lactation
Pregnancy Category: C
Administer to a pregnant woman only if potential benefit justifies potential risk to fetus
Lactation: Excretion in milk is unknown/not recommended; discontinue nursing during and for 60 days following therapy
A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA:Information not available.
Mechanism of Action
Recombinant humanized monoclonal antibody
Binds specifically to the EGF receptor (EGFR, HER1, c-ErbB-1) on both normal and tumor cells
Competitively inhibits the binding of EGF NS other ligands, such as TGF-alpha
Blocks phosphorylation and activation of receptor-associated kinases, resulting in inhibition of cell growth, induction of apoptosis, NS decreased matrix metalloproteinase ns VEGF production
AUC: increased in a greater than dose proportional manner as dose increased from 20 to 400 mg/m²
Peak Plasma Concentration
- Following a 2 hr infusion of 400 mg/m²: 184 mcg/mL (range: 92-327 mcg/mL)
- Following a 1 hr infusion of 250 mg/m²: 140 mcg/mL (range 120-170 mcg/mL)
Vd: 2-3 L/m²
Half-Life: 114 hr (range 75-188 hr); 97 hr (range 41-213 hr), following 400 mg/sq.meter IV over 2 hr
Clearance: decreased from 0.08 to 0.02 L/hr/sq.meter as dose increased from 20 to 200 mg/m² plateaus at doses >200 mg/m²
- Colorectal cancer expressing with KRAS wild-type respond more favorably to regimens that include anti-EGFR antibodies (cetuximab, panitumumab); whereas, the presence of KRAS mutation (codon 12 or 13) showed an absence of biological and clinical activity for the anti-EGFR antibody treatment
- Strongly recommended that patients with metastatic CRC who are being considered for treatment with anti-EGFR antibody therapy should be tested for the presence of a KRAS mutation prior to the administration of therapy (NCCN guidelines)
Non-small cell lung cancer (investigational)
- Presence of EGFR mutations does not appear to predict response to treatment with the EGFR monoclonal antibody cetuximab, but clinical trials have been conflicting
- An ongoing study is underway to examine prospectively whether high EGFR protein expression can be used as a predictor of treatment response to cetuximab
Genetic testing laboratories
- The following companies are currently offering KRAS mutation status testing
- Clarient, Inc. (http://www.clarientinc.com)
- Caris Diagnostics (http://www.carisdx.com)
- DxS (http://www.dxsdiagnostics.com)
- Genzyme Genetics (http://www.genzymegenetics.com)
- LabCorp (http://www.labcorp.com)
- Response Genetics (http://www.responsegenetics.com)
Do not shake or dilute
Discard unused portion after 8 hr at room temp & 12 hr if refrigerated
- Draw up volume of a vial using a sterile syringe attached to an appropriate needle (a vented spike or other appropriate transfer device may be used)
- Fill a sterile evacuated container or bag such as glass containers, polyolefin bags (eg, Baxter Intravia), ethylene vinyl acetate bags (eg, Baxter Clintec), DEHP plasticized PVC bags (eg, Abbott Lifecare), or PVC bags
- Repeat procedure until the calculated volume has been put into the container; use a new needle for each vial
- Admin through a low protein binding 0.22-micron in-line filter (placed as proximal to pt. as practical)
- Affix infusion line & prime before starting infusion
- Infuse initial dose over 120 min; Subsequent doses infused over 60 min, Max infusion rate is 10 mg/min
- Use NS to flush line at the end of infusion
- Draw up volume of vial using a sterile syringe attached to an appropriate needle (a vented spike may be used)
- Place the syringe into syringe driver of a syringe pump and set rate
- Admin through a low protein binding 0.22-micron in-line filter rated for syringe pump use (placed as proximal to pt. as practical)
- Connect up infusion line & start infusion after priming the line
- Repeat procedure until calculated volume infused, Use a new needle and filter for each vial
- Infuse initial dose over 120 min, Subsequent doses infused over 60 min, Max infusion rate is 10 mg/min
- Use NS to flush line at end of infusion, Piggybacked to infusion line
Following infusion, a 1 hr observation period is recommended
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