2 weekly Cetuximab in combination with OxMdG Chemotherapy 1 st line Metastatic Colorectal Cancer

Transcription

1 Cetuximab in Combination with Oxaliplatin Modified DeGramont for the 1 st line treatment of Metastatic Colorectal Cancer DRUG ADMINISTRATION SCHEDULE Day Drug Daily Dose Route Diluent and rate Day 1 Cetuximab 500mg/m 2 Intravenous Day 1 Chlorpheniramine 10mg IV Bolus Day 1 Paracetamol 1000mg ORAL Day 1 Dexamethasone 8mg ORAL Day 1 Glucose 5% 500ml Infusion Ondansetron 8mg Oral Calcium Leucovorin (folinic acid) 350mg IV Oxaliplatin 85mg/ m 2 IV Infusion 500ml Sodium Chloride 0.9% over 2 hours Fast Running for Line Flush 250ml Glucose 5% over 2 hours 250ml Glucose 5% over 2 hours concurrent with folinic acid Dextrose 5% 500ml Infusion Line Flush 5 Fluorouracil 400 mg/ m 2 IV bolus Over 5 minutes 5 Fluorouracil 2400 mg/ m 2 via infusor device Sodium Chloride 0.9% over 46 hours Day 3 Attend ward/ clinic for removal of 5-FU infusor device **If patient reacts during first administration consider adding steroid pre-medication on subsequent cycles (e.g. hydrocortisone 100mg IV or dexamethasone 20mg IV) NUMBER OF DAYS PER CYCLE 14 days until disease progression Cetuximab with OxMdG for the 1st line treatment of Metastatic Colorectal Cancer Page 1 of 7

2 APPROVED INDICATIONS Approved for use on the National Cancer Drug Fund List for patients who meet the following criteria: 1. Application made by and first cycle of systemic anti-cancer therapy to be prescribed by a consultant specialist specifically trained and accredited in the use of systemic anti-cancer therapy 2. Metastatic colorectal cancer 3. 1 st line indication 4. Patients with wild type RAS 5. Given in combination with the FOLFOX4 or FOLFOX6 or OxMdG chemotherapy regimens 6. Cetuximab given as a 2 weekly regimen at a dose of 500mg/m 2 7. Not eligible for NICE TA176 approved indications OR b. Eligible for treatment under TA176 and no progression after receiving the approved 16 weeks treatment with Cetuximab but unsuitable for surgery and meeting criteria No previous treatment with cetuximab or Panitumumab (unless meeting condition 7b) Note: Cetuximab is not approved for use as 1 st line treatment with any other oxaliplatin based regimens or upfront single agent fluoropyrimidine chemotherapy. Specifically in this setting cetuximab is not to be used with capecitabine and oxaliplatin combinations. Note: If excessive toxicity with oxaliplatin, cetuximab can be continued with a fluoropyrimidine alone until disease progression only No treatment breaks of more than 4 weeks are allowed. Should treatment breaks be required, then an Individual Funding Request must be submitted as per CDF processes. 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. *If acute cholinergic syndrome appears atropine sulphate should be administered unless clinically contraindicated. The manufacturer recommends the use of prophylactic atropine sulphate with subsequent doses of Irinotecan. RECOMMENDED TAKE HOME MEDICATION Ondansetron 8mg twice daily for 2-3 days Dexamethasone 4mg twice daily for 1-3 days Metoclopramide 10-20mg three to four times daily as required Loperamide as required (4mg after first loose stool and 2mg every 2 hours, to a maximum of 16 (2mg) tablets in 24 hours) Cetuximab with OxMdG for the 1st line treatment of Metastatic Colorectal Cancer Page 2 of 7

3 INVESTIGATIONS / MONITORING REQUIRED FBC, U&Es, LFT s. Magnesium and tumour markers as appropriate prior to each course of chemotherapy. There should not be a need to repeat all tests on day 15. Where CEA is elevated this should be measured before each cycle (no need to await result before proceeding with treatment). ASSESMENT 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 Before each cycle as appropriate NURSE / PHARMACIST LED REVIEW On cycles where not seen by clinician ADMINISTRATION NOTES Cetuximab 500mg/m 2 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, allergyrelated oedema, angio- oedema, hypotension, anaphylaxis) Action required Reduce Cetuximab infusion rate by 50% and monitor for worsening of symptoms. Ensure infusion rate does not exceed 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. Cetuximab with OxMdG for the 1st line treatment of Metastatic Colorectal Cancer Page 3 of 7

4 Patient requires semi-permanent IV access for this treatment, e.g. PICC line/ Hickman catheter Note: A variety of calcium folinate doses have been used in clinical trials, e.g. 200mg/m2 with max dose 350mg or 175mg Calcium LevoFolinate or 350mg Calcium Folinate. To enable a convenient, cost effective single vial dose, 300mg is recommended. Patients should be warned that on rare occasions they may experience an infusion reaction several hours after cetuximab Pulse, Respiration, Blood Pressure and Temperature must be measured during and I hour following infusion.bronchospasm can occur. * If severe laryngeal spasm occurs consider increasing Oxaliplatin infusion to 6 hours As with all platinum based chemotherapy, patients may experience allergicreaction during administration. The following table is intended to helpdifferentiate between Platinum Hypersensitivity and Laryngo-pharyngeal Dysesthesia during or following Oxaliplatin infusion. Clinical Symptoms Laryngo-pharyngeal Platinum Hypersensitivity Dysesthesia Dyspnea Present Present Bronchospasm Absent Present Laryngospasm Absent Present Anxiety Present Present O 2 saturation Normal Decreased Difficulty swallowing Present (loss of sensation) Absent Pruritus Absent Present Cold induced symptoms Yes No Blood pressure Normal or Increased Normal or Decreased Treatment Anxiolytics; observation in a controlled clinical setting until symptoms abate or at physician s discretion Oxygen, steroids, epinephrine, bronchodilators; Fluids and vasopressors if appropriate EXTRAVASATION See Local Guidelines TOXICITIES Peripheral neurotoxicity very common with Oxaliplatin. (dose limiting toxicity) Myleosuppression Cold induced parathesia Nausea and Vomiting Allergic reaction Diarrhoea Stomatitis Palmar/Plantar Erythrodysesthesia Darkening/discoloration of veins Cardiotoxicity - Occasionally patients may experience coronary artery spasm Laryngopharyngeal dysethesia Infusion reactions to Cetuximab Rash / skin reaction to Cetuximab Cetuximab with OxMdG for the 1st line treatment of Metastatic Colorectal Cancer Page 4 of 7

5 DOSE MODIFICATION Haematological Toxicity: Cetuximab does not normally cause myelosuppression, but is associated with anaemia in up to 10% of patients Delay 1 week if ANC < 1.5 and Platelets < 75 to 100 Grade III/IV ANC delay chemotherapy until recovered, then proceed at 20% 5FU If delay > 1 week or delay 2 weeks or greater occurs, reduce the 5FU dose (bolus & infusional) by 20%. Continue at the reduced dose for subsequent cycles unless other toxicity occurs. If further delay(s) for bone marrow suppression occur despite a 20% dose, consider a further 20% dose Non Haematological toxicity De GRAMONT Stomatitis PPE Grade I Grade II Grade III Grade IV Commence corsodyl mouth wash, nystatin No change. Advise E45 or aqueous cream Mouth care + Delay treatment until recovered Delay treatment until recovered with a 20% 5FU dose with a 20% 5FU dose with a 40% 5FU dose with a 40% dose Diarrhoea Loperamide 4mg initially, then 2mg after each motion Despite loperamide treatment: delay treatment until with a 20% 5FU dose with a 20% 5FU dose recovered. Discontinue or restart with a 20% dose (Discuss with SpR/Consultant) Renal function Cetuximab is not renally excreted If GFR falls to less than 30mls/min Oxaliplatin is contra-indicated Neurotoxicity: Cold related paraesthesia of hands/feet or dyseasthesia/laryngeal spasm syndrome last a few hours and do not require treatment or dose. If severe laryngeal spasm occurs consider increasing Oxaliplatin infusion to 6 hours If symptoms persist for 14 days and/or there is pain, functional loss, omit Oxaliplatin and continue with 5FU/FA until fully recovered, then restart Oxaliplatin at 20% dose. Cetuximab with OxMdG for the 1st line treatment of Metastatic Colorectal Cancer Page 5 of 7

6 Skin Reactions Grade 1 Grade 2 Grade 3 CTC (v2) definition Macular or popular eruption/erythema without symptoms Delay Cetuximab (continue other chemotherapy) Treatment Macular or popular eruption/erythema with pruritis or other symptoms; localised desquamation or other lesions covering <50% of body Symptomatic generalised erythroderma or macular, popular or vesicular eruption or desquamation covering >50% of body No No Yes see below Topical anti-acne cream (eg benzoyl peroxide) for face. Salicylic acid in alcoholic lotion for chest/back As grade 1 plus menthol in aqueous cream. Oral antihistamine and oral tetracycline (for 3 months) As grade 2 plus saline compresses if required. Systemic or topical steroids for treatment of rash are not generally advised. Patients on tetracyclines should be advised to avoid prolonged exposure to the 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. Occurrence of Grade 3 Toxicity Dose once resolved to grade 2 or better First 250mg/m 2 Second 200mg/m 2 Third 150mg/m 2 Fourth Discontinue treatment If skin toxicity has not resolved at Grade 2 or better within 3 weeks, discontinue Cetuximab TREATMENT LOCATION Cancer Centre or Cancer Unit where there is an Oncologist with a specialisation in colorectal patients as appropriate. REFERENCES: Van Cutsem, E et al; NEJM 2009; 360: Bokemeyer, C et al; JCO 2009; 27 (5): Bechstein, W et al; ASCO Proceedings 2009, Abstract No 4091 Rash advice adapted from HER1/EGFR Inhibitor Rash Management Forum, 2005 Tabernero, J et al; JCO 2006; 24 (18 suppl): 142s: abstract 3085 (2-weekly cetux) Cetuximab with OxMdG for the 1st line treatment of Metastatic Colorectal Cancer Page 6 of 7

7 Document Title: Document No: Author: Approved by: Due for Review: Summary of Changes Cetuximab (2 Weekly) in combination with OxMdG for the 1 st line treatment of Metastatic Colorectal Cancer NCDF Current Version: 1.0 Mandy Nagra Approval NHS England CNTW Area Signature* Steve Williamson Date Area Team Cancer Pharmacist Approved: 31 March st March 2016 Cetuximab with OxMdG for the 1st line treatment of Metastatic Colorectal Cancer Page 7 of 7