Regimen : Cetuximab ICD10 Codes pre-fixed with C18, C19, C20

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1 Regimen : Cetuximab ICD10 Codes pre-fixed with C18, C19, C20 Indications First-line metastatic, k-ras wild-type colorectal cancer in combination with standard chemotherapy (in patients otherwise ineligible for cetuximab via NICE guidelines / entry into clinical trials) Second-line metastatic, EGFR and Antibody naïve, k-ras wild-type colorectal cancer in combination with standard chemotherapy Third or subsequent line after failure of oxaliplatin and irinotecan in k- ras wild type colorectal metastatic colorectal cancer in combination with irinotecan (or single agent where further irinotecan contraindicated). (For performance status 0 and 1 patients only) This indication is NOT approved by NICE in these settings and may only be used with funding from the Cancer Drugs Fund Regimen detail Regimen 1 (weekly) Day Drug Dose Route Cycle 1 only 1 Cetuximab (see pre-medication section) Cycle 2 onwards Regimen 2 (every 14 days) 400mg/m 2 * IV infusion 1 Cetuximab 250mg/m 2 IV infusion OR Note: Two-weekly dosing of cetuximab is unlicensed. Cycle 1 only 1 Cetuximab (see pre-medication section) Cycle 2 onwards 400mg/m 2 * IV infusion 8 Cetuximab 250mg/m 2 IV infusion 1 Cetuximab 500mg/m 2 IV infusion Controlled document Document Number Version Number Page 1 of 6

2 Administration This regimen may be given together with Irinotecan (ASWCS11 GI012) at clinician discretion. In this combination, cetuximab is administered first. Cetuximab may be diluted in sodium chloride 0.9% or administered undiluted. Administer the first dose (i.e. Cycle 1, Day 1) of cetuximab over 2 hours. Subsequent doses may be administered over 60 minutes. If Regimen 2 is used, the 500mg/m 2 dose should be given over 2 hours or at a rate of 10mg/min, whichever is longer. Pulse, respiratory rate, blood pressure and temperature must be monitored during and for one hour following the infusion. Note: the summary of product characteristics for cetuximab recommends that an interval of at least 1 hour be observed between the completion of the cetuximab infusion and the administration of chemotherapy. However, this interval may be omitted at the discretion of the treating clinician. Cetuximab infusion reactions should be managed as outlined in the table below: Frequency Weekly or two weekly Maximum 12 cycles or until disease progression Extravasation Cetuximab is neutral (Group 1) Premedication Emetogenicity Additional recommended Patients MUST receive pre-medication with an antihistamine and corticosteroid prior to cycle 1. The recommended pre-medication for cycle 1 and all subsequent cycles is: Chlorphenamine 10mg IV bolus Paracetamol 1000mg PO Ranitidine 150mg PO Dexamethasone 8mg IV bolus This regimen has low emetogenic potential refer to local protocol Prophylaxis for skin toxicity should be routinely prescribed: Doxycycline 100mg bd Controlled document Document Number Version Number Page 2 of 6

3 supportive medication Pre-treatment evaluations Regular investigations Standard limits for administration to go ahead if blood results not within range, authorisation to administer must be given by prescriber/consultant FBC U+E Mg 2+ Ca 2+ LFT CEA FBC U+E Mg 2+ Ca 2+ LFT E45 topically all over body once daily Hydrocortisone 1% topically to face and hands twice daily Sun block (Factor 15-30) applied to face as required Loperamide for diarrhoea: 4mg at the first loose stool and then 2mg every 2 hours until diarrhoea-free (for up to 48 hours). Pliazon cream may be used for the skin rash associated with cetuximab infusions. It is supplied free of charge by the manufacturers. Give magnesium and calcium supplements if hypomagnesaemia or hypocalcaemia occur. CEA (perform monthly) CT scan Neutrophil count 1.0 x 10 9 /L Platelet count 75 x 10 9 /L Creatinine clearance Bilirubin Results valid for 72 hrs Perform after 6 cycles of treatment 50mL/min 1.5 x ULN Dose modifications Haematological toxicity Renal impairment N/A Deteriorating organ function should be discussed with the consultant as this may be a sign of disease progression. Hepatic impairment NCI Common toxicity criteria There is little experience of administering cetuximab in patients with renal impairment. Consider dose reduction if CrCl <10mL/min. Deteriorating organ function should be discussed with the consultant as this may be a sign of disease progression. There is little experience of administering cetuximab in patients with hepatic impairment. Hepatic insufficiency is unlikely to require dose reduction. Toxicity Definition Dose adjustment Hypomagnesaemia Unsymptomatic, mmol/L Symptomatic or Correct with oral supplementation Correct with intravenous Controlled document Document Number Version Number Page 3 of 6

4 <0.4mmol/L supplementation; ECG monitoring required. If magnesium fails to rectify on magnesium supplementation, it may be necessary to give supplementary calcium. Skin Reactions Grade1 Continue cetuximab treatment. Grade 2 Topical anti-acne cream (eg benzoyl peroxide) for face. Salicylic acid in alcoholic lotion for chest/back Continue cetuximab treatment. As for Grade 1 plus menthol in aqueous cream. Oral antihistamine and oral tetracycline (for 3 months) Grade 3 First occurrence: defer until Grade 2. Resume at full dose. Second occurrence: defer until Grade 2. Resume at 200mg/m 2 (or 400mg/m 2 if giving cetuximab fortnightly). Third occurrence: defer until Grade 2. Resume at 150mg/m 2 (or 300mg/m 2 if giving cetuximab fortnightly). Fourth occurrence: discontinue. Systemic or topical steroids (apart from Hydrocortisone 1% as described above) for treatment of rash are not generally advised. Patients on tetracyclines should be advised to avoid prolonged exposure to sun. Adverse effects the contents of the table indicate the adverse effects that should be documented on consent to treatment forms Significant drug interactions For full details consult product literature/reference texts 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. Allergic or Hypersensitivity Reactions Rare but serious side effects Interstitial lung disease Deep Vein Thrombosis; pulmonary embolism Other See Administration section above. Frequently occurring side effects Infusion-related reactions Hypomagnesaemia Diarrhoea Nausea & vomiting Hypocalcaemia Headache; increased liver enzymes Skin reactions and nail disorders No known interactions when cetuximab is used as monotherapy. Controlled document Document Number Version Number Page 4 of 6

5 Comments Cumulative Doses References Magnesium and calcium levels should be monitored in patients receiving this regimen and calcium and/or magnesium supplementation should be provided if hypocalcaemia and/or hypomagnesaemia occur. N/A Cunningham D, Humblet Y, Siena S, Khayat D, Beliberg H, Santoro A, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med (4): Sobrero AF, Maurel J, Fehrenbacher L, Scheithauer W, Abubakr YA, Lutz MP, et al. EPIC: Phase III Trial of Cetuximab Plus Irinotecan After Fluoropyrimidine and Oxaliplatin Failure in Patients with Metastatic Colorectal Cancer. J Clin Oncol 2008; 26 (14): Di Fiore F, Blanchard F, Charbonnier F, Le Pessot F, Lamy A, Galais MP, et al. Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy. Br J Cancer. 2007;96(8): Bokemeyer C, Bondarenko I, Makhson A, Hartmann JT, Aparicio J, de Braud F, et al. Fluorouracil, Leucovorin, and Oxaliplatin With and Without Cetuximab in the First-Line Treatment of Metastatic Colorectal Cancer. J Clin Oncol 2009; 27 (5): Van Cutsem E, Köhne CH, Láng I, Folprecht G, Nowacki MP, Cascinu S, et al.cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol (15): National Institute for Health and Clinical Excellence. Technology Appraisal 176. Cetuximab for the first-line treatment of metastatic colorectal cancer. [internet] accessed 14/01/2011, Daniels S. North London Cancer Network. Dose adjustment for cytotoxics in hepatic impairment [internet]. accessed 10/11/2011 available at %20Dosage%20adjustment%20for%20cytotoxics.doc Daniels S. North London Cancer Network. Dose adjustment for cytotoxics in renal impairment [internet]. accessed 10/11/2011 available at %20Dosage%20adjustment%20for%20cytotoxics.doc Baxter K, editor. Stockley s Drug Interactions. Pharmaceutical Press; Accessed online on 06/05/09 available at Allwood M, Stanley A, Wright P, editors. The cytotoxics handbook. 4 th ed. Radcliffe Medical Press Summary of Product Characteristics Erbitux 5mg/ml solution for infusion (Merck Serono) [internet]. accessed 26/01/2012 available from North of England Cancer Network. Cetuximab+FOLFOX (Oxaliplatin DeGramont) Protocol [internet]. Accessed 05/08/2011 available from al Central South Coast Cancer Network. Capecitabine-Cetuximab-Oxaliplatin Protocol [internet]. Accessed 02/09/2011 available from Document title Cetuximab Document number ASWCS12 GI027 Approval date 07/01/2013 Written by Stephen Falk, Consultant Clinical Oncologist BHOC Checked by Georgina Holmes, Pharmacist UHBristol NHSFT Authorised by Jeremy Braybrooke, Chair ASWCS Network Chemotherapy Group Review date 07/01/2015 Document reviewed by Controlled document Document Number Version Number Page 5 of 6

6 Version number Summary of changes 0.2.a Version Controlled document Document Number Version Number Page 6 of 6