NECN CHEMOTHERAPY HANDBOOK PROTOCOL
Single Agent, 2 Weekly Cetuximab
DRUG ADMINISTRATION SCHEDULE
Day
Drug
Daily Dose
Route
1
Chlorpheniramine
10mg
IV bolus
1
Paracetamol
1000mg
ORAL
1
Ranitidine
150mg
ORAL
1
Cetuximab
500mg/m2
Intravenous
15
Chlorpheniramine**
10mg
IV bolus
15
Paracetamol
1000mg
ORAL
15
Ranitidine
150mg
ORAL
15
Cetuximab
500mg/m2
Intravenous
Diluent & Rate
500ml Sodium Chloride
0.9% over 2 hours
500ml Sodium Chloride
0.9% 2 hours
*First cycle given over longer period, If patient reacts during first administration
consider adding steroid pre-medication on subsequent cycles (e.g. hydrocortisone
100mg IV or dexamethasone 20mg IV).
CYCLE LENGTH AND NUMBER OF DAYS
28 days until disease progression
APPROVED INDICATIONS
For patients with KRAS wildtype metastatic colorectal cancer as a single agent or in
combination with chemotherapy for either 1st, 2nd or 3rd line treatment given until
disease progression where approved by the Cancer Drug Fund.
ELIGIABILITY CRITERIA
 The tumour has been confirmed to demonstrate k-ras wild-type by a recognised
assay.
 No previous cetuximab
EXCLUSION CRITERIA
Patients with k-ras mutations
PREMEDICATION
Patients MUST receive pre-medication with a Paracetamol, ranitidine and
antihistamine prior to the first cycle of Cetuximab. Administration of Paracetamol,
Ranitidine and antihistamine is recommended on all other cycles. Some patients
may require pre-medication with a cortico-steroid.
RECOMMENDED TAKE HOME MEDICATION
No take home medication will normally be required.
INVESTIGATIONS / MONITORING REQUIRED
FBC, U&E, LFT’s prior to each dose. Magnesium & tumour markers as appropriate
prior to each four week course of treatment.
Single Agent, 2 Weekly Cetuximab
Issue Date 27.02.13
Expiry Date 28.02.15
NECN CHEMOTHERAPY HANDBOOK PROTOCOL
Single Agent, 2 Weekly Cetuximab
Where CEA is elevated this should be measured before each cycle (no need to await
result before proceeding with treatment).
ASSESSMENT OF RESPONSE
Tumour size and patient symptomatic response to be assessed at appropriate
intervals. All patients must have radiological assessment of disease no later than 8
weeks after starting Cetuximab and treatment must be discontinued if there is
evidence of disease progression.
REVIEW BY CLINICIAN
To be reviewed by either a Nurse, Pharmacist or Clinician before every cycle.
NURSE / PHARMACIST LED REVIEW
On cycles where not seen by clinician.
ADMINISTRATION NOTES
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Cetuximab 500mg/m2 can be administered faster than 2 hours provided the
infusion rate does not exceed 10mg/min.
Cetuximab 2 weekly schedule is unlicensed therefore used with prescriber
accepting responsibility for any drug reactions.
Sodium chloride 0.9% must be used for line flushing with Cetuximab.
Cetuximab (as with all monoclonal antibodies) can cause infusion reactions.
Administration must only take place in facilities with resuscitation facilities.
Management of Cetuximab infusion reactions is outlined in the table below:
CTC Grade Allergic / Infusion
Related Reaction
Grade 1 – mild
(Transient rash during infusion, drug
fever < 38°C)
Grade 2 – moderate
(Rash during infusion, flushing, urticaria,
dyspnoea, drug fever ≥
38°C)
Grade 3 or 4 – severe or life threatening
(Symptomatic bronchospasm, with or
without urticaria, parenteral medication
indicated, allergy-related oedema,
angiooedema, hypotension, anaphylaxis)
Action required
Reduce Cetuximab infusion rate by 50%
and monitor for worsening of symptoms.
Ensure infusion rate does not exceed
240mins (4hours). Use lower rate on all
subsequent infusions.
Stop Cetuximab infusion. Resume at
50% of rate once symptoms have
resolved or reduced to Grade 1.
Continue to monitor closely for worsening
of symptoms. Use lower rate on all
subsequent infusions.
Stop infusion immediately.
Do not re-treat with Cetuximab
• Patients should be warned that on rare occasions they may experience an
infusion reaction several hours after cetuximab – they should be advised to seek
urgent medical help if this occurs.
Single Agent, 2 Weekly Cetuximab
Issue Date 27.02.13
Expiry Date 28.02.15
NECN CHEMOTHERAPY HANDBOOK PROTOCOL
Single Agent, 2 Weekly Cetuximab
Pulse, Respiration, Blood Pressure and Temperature must be measured during
and 1 hour following infusion.
TOXICITIES
• Allergic reaction
• Cardio-pulmonary arrest
• Rash / skin reaction to Cetuximab
• Hypomagnesia
• Pulmonary toxicity
DOSE MODIFICATION / TREATMENT DELAYS
Haematological toxicity:
Cetuximab does not normally cause myelosuppression, but is associated with
anaemia in up to 10% of patients.
Renal Function:
 Cetuximab is not renally excreted
Skin reactions:
CTC (v2)
definition
Delay Cetuximab
(other
chemotherapy
can continue)
Treatment
Grade 1
Macular or popular
eruption/erythema
without
symptoms
No
Grade 2
Macular or popular
eruption/erythema
with pruritis or
other symptoms;
localised
desquamation or
other lesions
covering <50% of
body
No
Grade 3
Symptomatic
generalised
erythroderma or
macular, popular or
vesicular eruption or
desquamation
covering >50% of
body
Topical anti-acne
cream (eg benzoyl
peroxide) for face.
Salicylic acid in
alcoholic lotion for
chest/back
As grade 1 plus
As grade 2 plus
menthol in aqueous saline compresses if
cream. Oral
required.
antihistamine and
oral tetracycline
(for 3 months)
Yes – see below
Systemic or topical steroids for treatment of rash are not generally advised.
Patients on tetracyclines should be advised to avoid prolonged exposure to sun.
Topical treatments can have a drying effect on the skin. Care should be taken to
avoid aggravating xerosis, especially when acne-like rash is fading or becoming
scaly. Switch to moisturising creams instead of alcoholic lotion or gel if this occurs.
Single Agent, 2 Weekly Cetuximab
Issue Date 27.02.13
Expiry Date 28.02.15
NECN CHEMOTHERAPY HANDBOOK PROTOCOL
Single Agent, 2 Weekly Cetuximab
Occurrence of Grade 3 Toxicity
First
Second
Third
Fourth
Dose once resolved to Grade 2 or better
250mg/m2
200mg/m2
150mg/m2
Discontinue treatment
If skin toxicity has not resolved to Grade 2 or better within 3 weeks
discontinue cetuximab
TREATMENT LOCATION
Can be given at Cancer Centre or Cancer Unit.
Not suitable for home administration.
REFERENCES:
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Tabernero J et al.,Cetuximab administered once every second week to patients with
metastatic colorectal cancer: a two-part pharmacokinetic / pharmacodynamic phase I
dose-escalation study. Ann OncoL; 21: 1537 – 1545 (2010)
Yuan Y et al.: Activity and tolerance of biweekly CapeOx-Cetuximab in first-line therapy
of metastatic colorectal cancer (mCRC) and K-RAS influences. ASCO GI Cancers
Symposium 2009 Abstract #341
Bouchahda M et al.: Feasibility of cetuximab given with a simplified schedule every 2
weeks in advanced colorectal cancer: a multicentre, retrospective analysis Med Oncol
28: S253-S258 (2011)
Roca J-M, Alonso V, Pericay C et al.: Cetuximab given every 2 weeks plus irinotecan is
an active and safe option for previously treated patients with metastatic colorectal
cancer. Chemotherapy 56, 142-146 (2010)
Martin-Martorell P et al.: Biweekly cetuximab and irinotecan in advanced colorectal
cancer patients progressing after at least one previous line of chemotherapy: results of a
phase II single institution trial. BJC 99: 455-458 (2008)
Jensen BV et al.: Cetuximab every second week with irinotecan in patients with
metastatic colorectal cancer refractory to 5-FU, oxaliplatin and irinotecan: KRAS
mutation status and efficacy. Journal of Clinical Oncology 28 (Suppl.): Abstract 3573
1.
Document Title:
2 weekly Cetuximab for mCRC
Document No:
CRP13U012
Author:
Approved by:
Due for Review:
Current
Version:
Steve Williamson
Consultant Pharmacist NECN
Approval
Signature*
Calum Polwart, Network Pharmacist
Date
Approved:
1.
22.02.2013
Feb 2015
Summary of
Changes
Single Agent, 2 Weekly Cetuximab
Issue Date 27.02.13
Expiry Date 28.02.15