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CETU(RT)

Cancer Type: Head and Neck  Intent: Curative
Regimen Category: Evidence-Informed
Funding:
New Drug Funding Program
    Cetuximab and Radiation - Locally Advanced Squamous Cell Carcinoma of the Head and Neck
A - Regimen Name

CETU(RT) Regimen
Cetuximab


Disease Site
Head and Neck

(Squamous cell)


Intent
Curative

Regimen Category
Evidence-Informed :

Regimen is considered appropriate as part of the standard care of patients; meaningfully improves outcomes (survival, quality of life), tolerability or costs compared to alternatives (recommended by the Disease Site Team and national consensus body e.g. pan-Canadian Oncology Drug Review, pCODR).  Recommendation is based on an appropriately conducted phase III clinical trial relevant to the Canadian context OR (where phase III trials are not feasible) an appropriately sized phase II trial. Regimens where one or more drugs are not approved by Health Canada for any indication will be identified under Rationale and Use.


Rationale and Uses

As combination treatment with radiation therapy for the initial treatment of locally or regionally advanced squamous cell head and neck cancer (Health Canada indication) without distant metastases, for patients who are unable to use cisplatin or carboplatin/5-FU due to a medical contraindication, and are receiving cetuximab concurrently with acceptable radiation schedules that plan to intensity radiation delivery (e.g. accelerated radiotherapy). Use with caution in patients with known cardiac disease.


Supplementary Public Funding

cetuximab
New Drug Funding Program (Cetuximab and Radiation - Locally Advanced Squamous Cell Carcinoma of the Head and Neck) (NDFP Website)

 
B - Drug Regimen

Loading Dose:

cetuximab
400 mg /m² IV over 2 hours † 1 week prior to radiotherapy

 

 

THEN, Maintenance Dosing:

cetuximab
250 mg /m² IV over 1 hour *† Weekly during radiotherapy
* Complete cetuximab infusion 1 hour prior to radiation therapy.   Maximum rate 10 mg/min.
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C - Cycle Frequency

REPEAT EVERY 7 DAYS
Continue for duration of radiotherapy (6-7 weeks) unless unacceptable toxicities

 
D - Premedication and Supportive Measures

Antiemetic Regimen:

Minimal


Febrile Neutropenia Risk:

Low

Premedications (prophylaxis for infusion reaction):

  • H1-receptor antagonist (e.g. diphenhydramine 50 mg IV) 30-60 minutes prior to the dose.
  • Corticosteroid IV 30-60 minutes prior to the dose.
  • Consider discontinuing pre-medications after the 2nd infusion based on clinical judgment and the presence/severity of IR.
 
E - Dose Modifications

Doses should be modified according to the protocol by which the patient is being treated. 

Dosage with toxicity

 

Action

Next cycle

Pneumonitis

Hold and investigate

Discontinue if confirmed

Keratitis

Hold and refer to ophthalmologist

Consider discontinuation

 

Dosage modification for skin toxicity:

Grade 3 or 4 Rash

Action

Outcome

Cetuximab

1st occurrence

Delay infusion

1 to 2 weeks

Improvement

Continue at 250mg/m2

No improvement

Discontinue

2nd occurrence

Delay infusion

1 to 2 weeks

Improvement

Reduce:  200mg/m2

No improvement

Discontinue

3rd occurrence

Delay infusion

1 to 2 weeks

Improvement

Reduce:  150mg/m2

No improvement

Discontinue

4th  occurrence OR any occurrence of SJS/TENS

Discontinue

 

Management of Infusion-related reactions:

Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions

Grade Management Re-challenge
1 or 2
  • Slow or stop infusion rate.
  • Manage the symptoms.

Restart: 

  • The infusion can be restarted at a slower rate (50% of the rate at which the IR occurred) once symptoms have resolved
  • Re-challenge with a reduced infusion rate of 50% at which the infusion reaction occurred. 
3 or 4
  • Stop treatment
  • Aggressively manage symptoms

Restart:

  • Once symptoms resolve, the infusion can be restarted at a slower rate, unless a serious reaction has occurred (i.e. vital signs compromised; anaphylaxis). 
  • Permanently discontinue (do not re-challenge). 

 



Hepatic Impairment

Population pharmacokinetics suggest no significant impact.


Renal Impairment

Population pharmacokinetics suggest no significant impact.


Dosage in the Elderly

Insufficient patients have been enrolled in head and neck studies to draw firm conclusions.

 

 

 


 
F - Adverse Effects

Refer to cetuximab drug monograph(s) for additional details of adverse effects


Most Common Side Effects 

Less Common Side Effects, but may be
Severe or Life-Threatening

  • Rash (may be severe)
  • Paronychia  
  • Hypomagnesemia
  • Abdominal pain       
  • Constipation, diarrhea 
  • Anorexia, stomatitis       
  • Headache, insomnia          
  • Fatigue         
  • Nausea, vomiting
  • Infusion reactions (may be severe)
  • Fever, pain
  • Infection (may be severe)
  • Cough, dyspnea
  • Arterial thromboembolism
  • Venous thromboembolism
  • GI perforation, obstruction or bleed
  • Pneumonitis
  • Pancreatitis
  • Keratitis
  • Neuropathy
 
G - Interactions

Refer to cetuximab drug monograph(s) for additional details

 
H - Drug Administration and Special Precautions

Refer to cetuximab drug monograph(s) for additional details


Administration:

  • Do not shake or further dilute the solution.
  • DO NOT ADMINISTER AS AN IV PUSH OR BOLUS.
  • Transfer undiluted solution into an empty Viaflex bag or an empty syringe, if using a syringe pump.
  • Administer the undiluted solution via a low protein binding 0.22-micrometer in-line filter. Piggybacking to the patient’s infusion line, infuse initial loading dose over 2 hours, and maintenance dose over 1 hour (maximum rate 10 mg/min). (May require infusion at slower rate in those who experienced infusion reactions).
  • Prime administration line with drug solution before infusion and may use NS to flush line at the end of infusion.
  • A 1-hour observation period is recommended following each cetuximab infusion. Longer observation periods may be required in those who experienced infusion reactions.
  • Should not be mixed or diluted with other drugs.
  • Discard any unused portion left in a vial 12 hours under refrigeration or 8 hours at room temperature, as the product contains no preservatives.

Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.


Contraindications:

  • Contraindicated in patients with known hypersensitivity to cetuximab, murine protein or any components of this product
  • Treatment of colorectal cancer in patients with RAS mutations or RAS unknown status

Other Warnings/Precautions:

  • Patients with a history of, or pre-existing keratitis, dry eyes or contact lens use
  • Patients with poor performance status, or cardiopulmonary disease are at increased risk of severe hypersensitivity
  • Cetuximab plus radiation therapy for head and neck cancer should be used with caution in patients who are over age 65, have poor performance status, known history of coronary artery disease, arrhythmias, congestive heart failure or receiving cardiotoxic agents as fatal events have been reported. 
     

Pregnancy/Lactation:

  • Cetuximab is not recommended for use in pregnancy.  Adequate contraception should be used by both sexes during treatment, and for at least 6 months after the last dose.

  • Breastfeeding is not recommended during cetuximab therapy for at least 60 days following last dose

  • Fertility effects: Unknown

 
I - Recommended Clinical Monitoring

Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.

Recommended Clinical Monitoring

  • CBC and renal function; baseline and at each visit
  • Electrolytes, including serum magnesium, potassium and calcium; baseline, at each visit and monthly for 2 months following completion of therapy
  • Clinical toxicity assessment for skin, GI, hypersensitivity, respiratory symptoms, fatigue and keratitis; at each visit
  • Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version


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J - Administrative Information

Approximate Patient Visit
First cycle; 2.5 hours; Subsequent cycles: 1.5 hours
Pharmacy Workload (average time per visit)
24.85 minutes
Nursing Workload (average time per visit)
55.595 minutes
 
K - References

Bonner JA, Harari PM, Giralt J, Cohen RB, Jones CU, Sur RK, et al. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomized trial, and relation between cetuximab-induced rash and survival. Lancet Oncol 2010;11(1):21-8.

Bonner, JA, Harari PM, Jiralt J, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Eng J Med 2006; 354; 567-78.
 
Cetuximab drug monograph, Cancer Care Ontario.

October 2019 Updated infusion reaction information in Premedication and Dose Modifications sections. Expanded Drug Administration and Special Precautions section.


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M - Disclaimer

Regimen Abstracts
A Regimen Abstract is an abbreviated version of a Regimen Monograph and contains only top level information on usage, dosing, schedule, cycle length and special notes (if available). It is intended for healthcare providers and is to be used for informational purposes only. It is not intended to constitute or be a substitute for medical advice, and all uses of the Regimen Abstract are subject to clinical judgment. Such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability, and Cancer Care Ontario disclaims all liability for the use of this information, and for any claims, actions, demands or suits that arise from such use.
Information in regimen abstracts is accurate to the extent of the ST-QBP regimen master listings, and has not undergone the full review process of a regimen monograph.  Full regimen monographs will be published for each ST-QBP regimen as they are developed.
Regimen Monographs
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.
While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.
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