NECN CHEMOTHERAPY HANDBOOK PROTOCOL

Transcription

1 DRUG ADMINISTRATION SCHEDULE First Cycle: Day Drug Daily Dose Route Diluent & Rate 1 Chlorphenamine 10mg IV bolus 1 Paracetamol 1000mg ORAL 1 Ranitidine 150mg ORAL 1 Dexamethasone 8mg IV bolus 1 Cetuximab 400mg/m 2 Intravenous Flush line with Sodium Chloride 0.9%, Wait 1 hour, then start Glucose flush 1 Glucose 5% Intravenous 0.9% over 2 hours 1 Ondansetron 8mg IV bolus Via glucose drip 1 Oxaliplatin 130mg/m 2 IV infusion 250ml 5% Glucose 1 5% Glucose line flush 1 to 15 Capecitabine 1000mg/m 2 ORAL 8 Chlorphenamine** 10mg IV bolus 8 Paracetamol 1000mg ORAL 8 Ranitidine 150mg ORAL 8 Cetuximab 250mg/m 2 Intravenous Twice daily for 14 days only (start on evening of day 1 and finish on morning of day 15) 15 Chlorphenamine** 10mg IV bolus 15 Paracetamol 1000mg ORAL 15 Ranitidine 150mg ORAL 15 Cetuximab 250mg/m 2 Intravenous *if using Calcium Levofolinate give half the dose. **If patient reacts during first administration consider adding steroid pre-medication on subsequent cycles if not giving dexamethasone as an anti-emetic. XELOX+Cetuximab Page 1 of 7

2 Other cycles: Day Drug Daily Dose Route Diluent & Rate 1 Chlorphenamine 10mg IV bolus 1 Paracetamol 1000mg ORAL 1 Ranitidine 150mg ORAL 1 Dexamethasone 8mg IV bolus 1 Cetuximab 250mg/m 2 Intravenous Flush line with Sodium Chloride 0.9%, Wait 1 hour, then start Glucose flush 1 Glucose 5% Intravenous 1 Ondansetron 8mg IV bolus Via glucose drip 1 Oxaliplatin 130mg/m 2 IV infusion 250ml 5% Glucose 1 5% Glucose line flush 1 to 15 Capecitabine 1000mg/m 2 ORAL 8 Chlorphenamine** 10mg IV bolus 8 Paracetamol 1000mg ORAL 8 Ranitidine 150mg ORAL 8 Cetuximab 250mg/m 2 Intravenous Twice daily for 14 days only (start on evening of day 1 and finish on morning of day 15) 15 Chlorphenamine** 10mg IV bolus 15 Paracetamol 1000mg ORAL 15 Ranitidine 150mg ORAL 15 Cetuximab 250mg/m 2 Intravenous *if using Calcium Levofolinate give half the dose. **If patient reacts during previous Cetuximab administration consider adding steroid premedication on subsequent cycles if not giving Dexamethasone as an anti-emetic. CYCLE LENGTH AND NUMBER OF DAYS 21 days for up to 5 cycles (total permitted 16 doses of Cetuximab) APPROVED INDICATIONS First line treatment of metatstatic colorectal cancer with liver only metastasis. XELOX+Cetuximab Page 2 of 7

3 ELIGIABILITY CRITERIA The primary colorectal tumour has been resected or is potentially operable. The metastatic disease is confined to the liver and is unresectable. The patient is fit enough to undergo surgery to resect the primary colorectal tumour and to undergo liver surgery if the metastases become resectable after treatment with Cetuximab. The manufacturer rebates 16% of the amount of Cetuximab used on a per patient basis. The tumour has been confirmed to demonstrate k-ras wild-type by a recognised assay. EXCLUSION CRITERIA Patients with baseline renal function less than 30ml/min (Creatinine Clearance) Patients incapable of managing oral chemotherapy themselves or with the assistance of a carer Patients with swallowing difficulties Patients with k-ras mutations PREMEDICATION Patients MUST receive pre-medication with 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 Ondansetron 8mgs x twice daily for 2 to 3 days Dexamethasone 4mgs x twice daily for 1 to 3 days Metoclopramide 10 to 20mgs three to four times daily as required Many patients will tolerate this regimen with out the need for Ondansetron and with shorter courses or reducing doses of Dexamethasone. Anti-emetic cover should be individualised based on emetogenic risk factors of individual patients. INVESTIGATIONS / MONITORING REQUIRED FBC, U&E LFT s, Magnesium & tumour markers as appropriate prior to each course of chemotherapy FBC on day 1 of chemotherapy, but not required for day 8 and 15. XELOX+Cetuximab Page 3 of 7

4 Where CEA is elevated this should be measured before each cycle (no need to await result before proceeding with treatment). ASSESSMENT OF RESPONSE Metastatic: Tumour size and patient symptomatic response 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 Cetuximab should be administered at a maximum rate of 10mg/min (600mg/hour), and a maximum infusion time of 240minutes. Sodium chloride 0.9% must be used for line flushing with Cetuximab. Oxaliplatin is incompatible with saline. Must use 5% Glucose as diluent and line flush 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. Pulse, Respiration, Blood Pressure and Temperature must be measured during and 1 hour following infusion. XELOX+Cetuximab Page 4 of 7

5 If diarrhoea is a problem give Loperamide 2-4 mg four times daily when required or codeine phosphate. Bronchospasm can occur. * If severe laryngeal spasm occurs consider increasing Oxaliplatin infusion to 6 hours As with all platinum based chemotherapy, patients may experience allergic reaction during administration. The following table is intended to help differentiate between Platinum Hypersensitivity and Laryngo-pharyngeal Dysesthesia during or following oxaliplatin infusion. Patients who have previously experienced Grade I or II Platinum Hypersensitivity should be pre-medicated with Ranitidine 50 mg IV in 50 ml NS over 20 minutes, and must receive both steroid and anti-histamine premedication as described above, consider increasing Dexamethasone to 20mg. Capecitabine should start on the evening of day 1 and continue until the morning of day 15. Capecitabine should be omitted if Grade II toxicity occurs. It can recommence (see Dose Reductions) if toxicity resolves, however the treatment should still stop on day 15. (i.e. Doses are omitted not delayed). Note: Grade II Toxicity includes: Diarrhoea defined as an increase of 4-6 stools per day or nocturnal stools. TOXICITIES Peripheral neurotoxicity very common with Oxaliplatin. (dose limiting toxicity) Myleosuppression Cold induced parathesia Nausea and Vomiting Allergic reaction Diarrhoea Stomatitis Hyperbilirubinemia Palmar/Plantar Erythrodysesthesia - Can be severe, patients must be forewarned Darkening/discoloration of veins Cardiotoxicity - Occasionally patients may experience coronary artery spasm Laryngopharyngeal dysethesia XELOX+Cetuximab Page 5 of 7

6 Infusion reactions to Cetuximab Rash / skin reaction to Cetuximab Contra-indicated in patients with severe hepatic impairment, a history of severe and unexpected reactions to fluoropyrimidine therapy, hypersensitivity. Avoid concomitant use with Allopurinol DOSE MODIFICATION / TREATMENT DELAYS Haematological toxicity: Delay treatment on day 1, 1 week if WBC < 3.0, ANC < 1.5 and Platelets < 100 If delay > 1 week delay patient will need a 20% dose reduction of oxaliplatin and capecitabine There is no requirement to delay day 8 or 15 Cetuximab based on full blood count. Renal Function: If GFR falls to less than 30mls/min oxaliplatin and capecitabine are contraindicated. GFR or CrCl 30-49ml/min reduce oxaliplatin to 50% and capecitabine to 75% of original doses. Non-Haematological Toxicity: No dose reduction should apply to oxaliplatin in case of PPE In case of Grade III/IV stomatitis or diarrhoea despite a 20% reduction of 5FU, oxaliplatin should be reduced by 20% Skin reactions: CTC (v2) definition Delay Cetuximab (other chemotherapy can continue) Treatment Grade 1 Grade 2 Grade 3 Macular or popular Symptomatic generalised Macular or popular eruption/erythema with pruritis or erythroderma or macular, popular eruption/erythema without other symptoms; localised or vesicular eruption or symptoms desquamation or other lesions desquamation covering >50% of covering <50% of body 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 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. XELOX+Cetuximab Page 6 of 7

7 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 to Grade 2 or better within 3 weeks discontinue Cetuximab. Neurotoxicity: Cold related paraesthesia of hands/feet or dyseasthesia/laryngeal spasm syndrome last a few hours and do not require treatment or dose reduction. 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 reduction. TREATMENT LOCATION Can be given at Cancer Centre or Cancer Unit. Not suitable for home administration. REFERENCES: FOCUS2 Trial Protocol. August 2003 (version 1.1) BCCA Protocol Summary for ADJUVANT Combination Chemotherapy for Stage III Colon Cancer Using Oxaliplatin, 5-Fluorouracil and Folinic Acid (Leucovorin). Reference: UGIAJFFOX. Mar 2006 Cassidy J et al (2004) XELOX (capecitabine plus oxaliplatin): active first-line therapy for patients with metastatic colorectal cancer. J Clin Oncol Jun 1;22(11): Document Control Document Title: Document No: Author: Approved by: XELOX+Cetuximab CRP09 CR016 Due for Review: Nov 2011 Summary of Changes Calum Polwart, Network Pharmacist Nick Wadd 1.0a Final Version Agreed Current Version: Approval Signature* Date Approved: 1.0a 16 Nov 09 XELOX+Cetuximab Page 7 of 7