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Regimen : XELOX/ CAPOX (Xeloda

(Capecitabine) and Oxaliplatin)Indications Adjuvant Stage III (Dukes C) colon cancer

Advanced metastatic colorectal cancer

Day Drug Dose Route

1 Oxaliplatin 130mg/m

2

IV infusion

Regimen details

1-14 Capecitabine 1,000mg/m2 Twice Daily PO

Administration Administer Oxaliplatin in 250-500ml Glucose 5% over 2 hours.Ifpatients experience laryngo-pharyngeal dyaesthesia (seebelow), subsequent infusions should be should be given over 4-6 hours.

Infusions must be diluted in Glucose 5%as oxaliplatin is notcompatible with Sodium Chloride 0.9%. Lines must not bepiggybacked or flushed with Sodium Chloride 0.9% immediatelyafter the Oxaliplatin infusion.

Patients should be closely observed for platinumhypersensitivity reactions, particularly during the first andsecond infusions. Hypersensitivity reactions may occur within afew minutes following the initiation of the infusion of oxaliplatin.Facilities for the treatment of hypotension and bronchospasmmustbe available.

If hypersensitivity reactions occur, minor symptoms such asflushing or localised cutaneous reactions do not requirediscontinuation of therapy: the infusion may be temporarilyinterrupted and when symptoms improve re-started at a slower

infusion rate. Chlorphenamine 10mg IV may be administered.

Severe reactions, such as hypotension, bronchospasm orgeneralised rash/erythema require immediate discontinuation ofoxaliplatin and appropriate therapy.

Cryotherapy (ice cubes) should NOTbe used as they mayexacerbate oxaliplatin-induced pharyngo-laryngealdyaesthesias. Similarly, laryngo-pharyngeal dyaesthesia may beexacerbated by exposure to cold air. If this occurs duringinfusion, stop infusion immediately and observe patient. Check

oxygen saturation: if normal, an anxiolytic agent (e.g.lorazepam1mg SC/PO/IV) may be given. The infusion can then berestarted at a slower rate (between 4-6 hours)

Capecitabine tablets should be swallowed whole with waterwithin 30 minutes of eating a meal. Available as 500mg and150mg tablets. Doses should be banded in accordance with thetable below:

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Dose level 1000mg/m2bdBody SurfaceArea (m2) Dose (mg) to be given TWICE DAILY for 14

days followed by a 7 day break each cycle

1.24 1.38 1300

1.39 1.47 1450

1.48 1.57 1500

1.58 1.72 1650

1.73 1.89 1800

1.90 2.07 2000

2.08 2.22 2150

2.23 2300

Frequency Every 21 daysMaximum 8 cycles

Extravasation Oxaliplatin is an exfoliant (Group 4)Capecitabine is an oral agent.

Premedication None usually required.Patients who have previously experienced Grade 1 or 2 platinumhypersensitivity should be pre-medicated with as follows:

45 minutes prior to Oxaliplatin: Dexamethasone 20mg IV bolus 30 minutes prior to Oxaliplatin: Chlorphenamine 10mg IV bolus

and Ranitidine 50 mg IV bolus diluted in at least 20ml SodiumChloride 0.9% and given over at least 2 minutes.

Patients who develop peripheral neuropathy may be considered forcalcium gluconate 1g and magnesium sulphate 1g given together in250mL 5% Glucose IV over 20 minutes pre- and post-oxaliplatininfusion. Caution is required in giving this treatment to patients withknown hypercalcemia or those receiving digoxin or thiazide diuretics.

Emetogenicity This regimen has moderate-high emetogenic potential refer to localprotocol

Additionalrecommendedsupportivemedication

Mouthwashes as per local policy.

Loperamide 4mg po stat then 2mg prn if diarrhoea develops.

Pyridoxine 50 mg tds reduces the severity of plantar-palmarerythrodyesthesia (PPE). It should be given for any grade PPEand should be continued until the end of treatment.

FBC Baseline results valid for 14 days

U+E (incl SrCr) Baseline results valid for 14 days

Pre-treatmentevaluation

LFT Baseline results valid for 14 days

FBC Results valid for 72 hrsU+E (incl SrCr) Results valid for 7 days

LFT Results valid for 7 days

Ca2+ and Mg2+ Results valid for 7 days

Regularinvestigations

CT scan Perform after 4 cycles of treatment

Neutrophil count 1.0 x109/L

Platelet count 75 x109/L

Creatinine clearance 50 ml/min

Standard limits foradministration to goahead if blood resultsnot within range,authorisation to administermustbe given byprescriber/consultant

Bilirubin

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Dose modifications

Haematologicaltoxicity

If at any time during the previous cycle, infection/fever associated withneutropenia has occurred treat as follows:

Grade 3 febrile neutropenia (neutrophil count

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Acute Cold-related Dysaesthesia (CRD): Many patients experiencetransient paraesthesia of hands & feet. Onset is during or within hours ofinfusion, and resolves within minutes to a few days. Symptoms areexacerbated by cold, so patient should be advised to avoid cold. Does notrequire treatment or dose reduction.Acute laryngopharyngeal dysaesthesia: Some patients experiencelaryngopharyngeal dysaesthesia (unpleasant sensations in the throat).Onset is during or within hours of infusion, and resolves within minutes to

a few days. Symptoms are exacerbated by cold, so patient should beadvised to avoid cold drinks. Does not require treatment or dose reduction.

Grade 1:Minimalskin changes ordermatitis (e.g.,erythema, edema,or hyperkeratosis)without pain

100%

Grade 2: Skinchanges (e.g.,peeling, blisters,

bleeding, edema,or hyperkeratosis)with pain; limitinginstrumental ADL

1stappearance: delay until

resolved to Grade 1 and thenresume at 100%

2ndappearance: delay untilresolved to Grade 1 and thenresume at 75%3

rdappearance: delay until

resolved to Grade 1 and thenresume at 50%

Palmar-PlantarErythrodyaesthesia(Capecitabine)

Grade 3: Severeskin changes (e.g.,peeling, blisters,bleeding, edema,or hyperkeratosis)with pain; limiting

self care ADL

1stappearance: delay untilresolved to Grade 1 and thenresume at 75%2

ndappearance: delay until

resolved to Grade 1 and thenresume at 50%

3rdappearance: discontinueGrade 1 100%

Grade 2 1stappearance: delay untilresolved to Grade 1 and thenresume at 100%2

ndappearance: delay until

resolved to Grade 1 and thenresume at 75%3rdappearance: delay untilresolved to Grade 1 and thenresume at 50%

Grade 3 1

st

appearance: delay untilresolved to Grade 1 and thenresume at 75%2ndappearance: delay untilresolved to Grade 1 and thenresume at 50%3

rdappearance: discontinue

Diarrhoea/Mucositisand Stomatitis *(Capecitabine)

Grade 4 Discontinue

*Note that severe diarrhoea and/or severe mucositis early in the firsttreatment cycle can be the first presenting toxicity due to DPD enzymedeficiency. This can lead to potentially fatal neutropenia.

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Serious side effects Frequently occurring side effects

Myelosuppression (common) Peripheral Neuropathy

Cardiomyopathy / toxicity Diarrhoea

Secondary malignancy Palmar-plantar erythrodyaesthesia

Ovarian failure/infertility Alopecia (complete)

Nephrotoxicity Stomatitis/ Mucositis

Nausea and vomiting

Fatigue

Adverse effectsthe contents of the tableindicate the adverseeffects that should bedocumented on consentto treatment forms

Other dysgeusia, headache, dizziness

Significant druginteractions Forfull details consultproductliterature/reference texts

Warfarin/courmarin anticoagulantsAvoid use switch patients to lowmolecular weight heparin during treatment elevations in INR

Oxaliplatin:Aminoglycosides: increased risk of nephrotoxicity and possibly of ototoxicity-avoid concomitant useDiuretics: increased risk of nephrotoxicity and ototoxicity when platinumcompounds given with diuretics

Capecitabine:Phenytoin toxicity has occurred during concomitant capecitabine therapy monitor levels regularly.Sorivudine and its analogues co-administration causes increasedfluoropyrimidine toxicity which may be fatalAllopurinol A decrease in capecitabine activity as been shown when takenin combination of allopurinol. Avoid if possible.FolinatesAvoid concomitant use of folinic and folic acid enhanced toxicityof capecitabineAntacids the use of antacids with capecitabine can decrease absorption avoid.

Comments Dihydropyrimidine dehydrogenase (DPD) deficiency can result in severe

toxicity secondary to reduced fluorouracil metabolism avoid use ofcapecitabine in patients with known DPD deficiency

Cardiotoxicity has been associated with fluoropyrimidine therapy, with adverseevents being more common in patients with a prior history of coronary arterydisease. Caution must be taken in patients with a history of significant cardiacdisease, arrhythmias or angina pectoris.

Cumulative Doses N/A

References Cassidy J, Tabernero J, Twelves C, Brunet R, Butts C, Conroy T, et al.XELOX (Capecitabine Plus Oxaliplatin): Active First-Line Therapy forPatients With Metastatic Colorectal Cancer. J Clin Oncol 2004; 22(11): 2084-2091.

Daniels S. North London Cancer Network, Dose adjustment forcytotoxics in hepatic impairment [internet]. accessed 12/01/2011available at http://www.bopawebsite.org/tiki-download_file.php?fileId=621

Daniels S. North London Cancer Network, Dose adjustmentforcytotoxics in renal impairment [internet]. accessed 12/01/2011available at http://www.bopawebsite.org/tiki-download_file.php?fileId=620

Baxter K, editor. Stockleys Drug Interactions. Pharmaceutical Press;2009. Accessed online on 06/05/09 available athttps://www.medicinescomplete.com/mc/

Allwood M, Stanley A, Wright P, editors. The cytotoxics handbook. 4th

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ed. Radcliffe Medical Press . 2002.

Summary of Product Characteristics Oxaliplatin Hospira 5mg/mlconcentration for solution for infusion (Hospira) [internet]. accessed14/01/2011 available fromhttp://www.medicines.org.uk/EMC/medicine/20911/SPC

Summary of Product Characteristics Xeloda (Capecitabine)500mg and 150mg Tablets (Roche) [internet], accessed23/02/2011 available from

http://www.medicines.org.uk/EMC/medicine/4619/SPC/Xeloda/

Document title XELOX/ CAPOX (Xeloda

(Capecitabine) and Oxaliplatin)

Document number ASWCS11 GI022

Approval date 19/07/2011

Written by Stephen Falk, Consultant ClinicalOncologist BHOC

Checked by James Carr, Network Pharmacist,

ASWCSAuthorised by Jeremy Braybrooke, Chair ASWCS

Drugs and Therapeutics Committee

Review date 19/07/2013

Document reviewed by

Version number 1.1.a

Summary of changes Version

Steve FalkDigitally signed by Steve FalkDN: cn=Steve Falk, o, ou, email=james.carr@aswcs.nhs.

uk, c=GB

Date: 2011.07.27 15:10:45 +01'00'

James Carr

Digitally signed by James Carr

DN: cn=James Carr, o=ASWCS, ou=Network

Pharmacist, email=james.carr@aswcs.nhs.uk, c=GB

Date: 2011.07.27 15:11:11 +01'00'

Jeremy BraybrookeDigitally signed by Jeremy Braybrooke

DN: cn=Jeremy Braybrooke, o, ou,

email=james.carr@aswcs.nhs.uk, c=GB

Date: 2011.07.27 15:11:41 +01'00'