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Regimen : XELOX/ CAPOX (Xeloda (Capecitabine) and Oxaliplatin)

Indications
Regimen details

Administration

Controlled document

Day
1
1-14

Adjuvant Stage III (Dukes C) colon cancer


Advanced metastatic colorectal cancer
Drug
Dose
Route
Oxaliplatin
130mg/m2
IV infusion
2
Capecitabine
1,000mg/m Twice Daily
PO
Administer Oxaliplatin in 250-500ml Glucose 5% over 2 hours. If
patients experience laryngo-pharyngeal dyaesthesia (see
below), subsequent infusions should be should be given over 46 hours.

Infusions must be diluted in Glucose 5% as oxaliplatin is not


compatible with Sodium Chloride 0.9%. Lines must not be
piggybacked or flushed with Sodium Chloride 0.9% immediately
after the Oxaliplatin infusion.

Patients should be closely observed for platinum


hypersensitivity reactions, particularly during the first and
second infusions. Hypersensitivity reactions may occur within a
few minutes following the initiation of the infusion of oxaliplatin.
Facilities for the treatment of hypotension and bronchospasm
must be available.

If hypersensitivity reactions occur, minor symptoms such as


flushing or localised cutaneous reactions do not require
discontinuation of therapy: the infusion may be temporarily
interrupted and when symptoms improve re-started at a slower
infusion rate. Chlorphenamine 10mg IV may be administered.

Severe reactions, such as hypotension, bronchospasm or


generalised rash/erythema require immediate discontinuation of
oxaliplatin and appropriate therapy.

Cryotherapy (ice cubes) should NOT be used as they may


exacerbate oxaliplatin-induced pharyngo-laryngeal
dyaesthesias. Similarly, laryngo-pharyngeal dyaesthesia may be
exacerbated by exposure to cold air. If this occurs during
infusion, stop infusion immediately and observe patient. Check
oxygen saturation: if normal, an anxiolytic agent (e.g.lorazepam
1mg SC/PO/IV) may be given. The infusion can then be
restarted at a slower rate (between 4-6 hours)

Capecitabine tablets should be swallowed whole with water


within 30 minutes of eating a meal. Available as 500mg and
150mg tablets. Doses should be banded in accordance with the
table below:

Document Number
ASWCS11 GI022

Version Number

1.1.a

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Dose level 1000mg/m2 bd

Body Surface
Dose (mg) to be given TWICE DAILY for 14
Area (m2)
days followed by a 7 day break each cycle

Frequency
Extravasation
Premedication

Emetogenicity
Additional
recommended
supportive
medication
Pre-treatment
evaluation
Regular
investigations

Standard limits for


administration to go
ahead if blood results
not within range,
authorisation to administer
must be given by
prescriber/consultant

Controlled document

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

Every 21 days
Maximum 8 cycles
Oxaliplatin is an exfoliant (Group 4)
Capecitabine is an oral agent.
None usually required.
Patients who have previously experienced Grade 1 or 2 platinum
hypersensitivity 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 Sodium
Chloride 0.9% and given over at least 2 minutes.
Patients who develop peripheral neuropathy may be considered for
calcium gluconate 1g and magnesium sulphate 1g given together in
250mL 5% Glucose IV over 20 minutes pre- and post-oxaliplatin
infusion. Caution is required in giving this treatment to patients with
known hypercalcemia or those receiving digoxin or thiazide diuretics.
This regimen has moderate-high emetogenic potential refer to local
protocol

Mouthwashes as per local policy.


Loperamide 4mg po stat then 2mg prn if diarrhoea develops.
Pyridoxine 50 mg tds reduces the severity of plantar-palmar
erythrodyesthesia (PPE). It should be given for any grade PPE
and 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
LFT
Baseline results valid for 14 days
FBC
Results valid for 72 hrs
U+E (incl SrCr)
Results valid for 7 days
LFT
Results valid for 7 days
Ca2+ and Mg2+
Results valid for 7 days
CT scan
Perform after 4 cycles of treatment
Neutrophil count
1.0 x109/L
Platelet count
75 x109/L
Creatinine clearance
50 ml/min
Bilirubin
<1.5 x ULN

Document Number
ASWCS11 GI022

Version Number

1.1.a

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Dose modifications
Haematological
toxicity

Renal impairment

Hepatic
impairment

NCI Common
toxicity criteria

Controlled document

Neutrophil
count
1.0
0.5-0.9

Platelet
count
75
50-74

<0.5

25-49

<0.5

<25

Action

Dose modification
once count recovery
Full dose
Restart capecitabine at
full dose and oxaliplatin
at 100mg/m2

Go ahead
Stop capecitabine
and delay next
cycle until count
recovery
Stop capecitabine
and delay next
cycle until count
recovery
Stop capecitabine
and delay next
cycle until count
recovery

Restart capecitabine at
full dose and oxaliplatin
at 100mg/m2
Restart capecitabine at
full dose and oxaliplatin
at 65mg/m2.

If at any time during the previous cycle, infection/fever associated with


neutropenia has occurred treat as follows:
Grade 3 febrile neutropenia (neutrophil count <1.0x109/l), Restart
capecitabine at full dose and oxaliplatin at 100mg/m2
Grade 4 febrile neutropenia (neutrophil count <0.5x109/l), Restart
capecitabine at full dose and oxaliplatin at 100mg/m2.
Capecitabine
Oxaliplatin
CrCl (mL/min)
>50
100%
100%
30-49
75%
75%
<30
Contra-indicated
Omit
Capecitabine: Lack of information available. In patients with mild to moderate
hepatic dysfunction due to liver metastases (<3 x ULN bilirubin; <5 x ULN
AST/ALT). Probably no dose reduction necessary: clinical decision
Oxaliplatin: Little information available. Probably no dose reduction
necessary: clinical decision

Toxicity
Neurotoxicity
(Oxaliplatin)

Document Number
ASWCS11 GI022

Definition
Grade 1 paraesthesia
Grade 2 paraesthesia
persisting until next cycle
Grade 3 paraesthesia >7
days but resolved before
next cycle
Grade 3 paraesthesia
persisting until next cycle
or Grade 4 of any
duration

Version Number

1.1.a

Dose adjustment
100%
Reduce dose to 100mg/m2
Reduce dose to 100mg/m2

Discontinue oxaliplatin

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Acute Cold-related Dysaesthesia (CRD): Many patients experience


transient paraesthesia of hands & feet. Onset is during or within hours of
infusion, and resolves within minutes to a few days. Symptoms are
exacerbated by cold, so patient should be advised to avoid cold. Does not
require treatment or dose reduction.
Acute laryngopharyngeal dysaesthesia: Some patients experience
laryngopharyngeal 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 be
advised to avoid cold drinks. Does not require treatment or dose reduction.
Palmar-Plantar
Erythrodyaesthesia
(Capecitabine)

Grade 1:Minimal
skin changes or
dermatitis (e.g.,
erythema, edema,
or hyperkeratosis)
without pain
Grade 2: Skin
changes (e.g.,
peeling, blisters,
bleeding, edema,
or hyperkeratosis)
with pain; limiting
instrumental ADL

100%

1st appearance: delay until


resolved to Grade 1 and then
resume at 100%
2nd appearance: delay until
resolved to Grade 1 and then
resume at 75%
3rd appearance: delay until
resolved to Grade 1 and then
resume at 50%
Grade 3: Severe
1st appearance: delay until
skin changes (e.g., resolved to Grade 1 and then
resume at 75%
peeling, blisters,
2nd appearance: delay until
bleeding, edema,
resolved to Grade 1 and then
or hyperkeratosis)
resume at 50%
with pain; limiting
3rd appearance: discontinue
self care ADL
Diarrhoea/Mucositis Grade 1
100%
and Stomatitis *
Grade 2
1st appearance: delay until
(Capecitabine)
resolved to Grade 1 and then
resume at 100%
2nd appearance: delay until
resolved to Grade 1 and then
resume at 75%
3rd appearance: delay until
resolved to Grade 1 and then
resume at 50%
Grade 3
1st appearance: delay until
resolved to Grade 1 and then
resume at 75%
2nd appearance: delay until
resolved to Grade 1 and then
resume at 50%
3rd appearance: discontinue
Grade 4
Discontinue
* Note that severe diarrhoea and/or severe mucositis early in the first
treatment cycle can be the first presenting toxicity due to DPD enzyme
deficiency. This can lead to potentially fatal neutropenia.

Controlled document

Document Number
ASWCS11 GI022

Version Number

Page 4 of 6

Adverse effects

Serious side effects

the contents of the table


indicate the adverse
effects that should be
documented on consent
to treatment forms

Myelosuppression (common)
Cardiomyopathy / toxicity
Secondary malignancy
Ovarian failure/infertility
Nephrotoxicity

Significant drug
interactions For
full details consult
product
literature/reference texts

Comments

Cumulative Doses
References

Peripheral Neuropathy
Diarrhoea
Palmar-plantar erythrodyaesthesia
Alopecia (complete)
Stomatitis/ Mucositis
Nausea and vomiting
Fatigue
Other
dysgeusia, headache, dizziness
Warfarin/courmarin anticoagulants Avoid use switch patients to low
molecular weight heparin during treatment elevations in INR
Oxaliplatin:
Aminoglycosides: increased risk of nephrotoxicity and possibly of ototoxicityavoid concomitant use
Diuretics: increased risk of nephrotoxicity and ototoxicity when platinum
compounds given with diuretics
Capecitabine:
Phenytoin toxicity has occurred during concomitant capecitabine therapy
monitor levels regularly.
Sorivudine and its analogues co-administration causes increased
fluoropyrimidine toxicity which may be fatal
Allopurinol A decrease in capecitabine activity as been shown when taken
in combination of allopurinol. Avoid if possible.
Folinates Avoid concomitant use of folinic and folic acid enhanced toxicity
of capecitabine
Antacids the use of antacids with capecitabine can decrease absorption
avoid.
Dihydropyrimidine dehydrogenase (DPD) deficiency can result in severe
toxicity secondary to reduced fluorouracil metabolism avoid use of
capecitabine in patients with known DPD deficiency
Cardiotoxicity has been associated with fluoropyrimidine therapy, with adverse
events being more common in patients with a prior history of coronary artery
disease. Caution must be taken in patients with a history of significant cardiac
disease, arrhythmias or angina pectoris.
N/A

Controlled document

Frequently occurring side effects

Cassidy J, Tabernero J, Twelves C, Brunet R, Butts C, Conroy T, et al.


XELOX (Capecitabine Plus Oxaliplatin): Active First-Line Therapy for
Patients With Metastatic Colorectal Cancer. J Clin Oncol 2004; 22
(11): 2084-2091.
Daniels S. North London Cancer Network, Dose adjustment for
cytotoxics in hepatic impairment [internet]. accessed 12/01/2011
available at http://www.bopawebsite.org/tikidownload_file.php?fileId=621
Daniels S. North London Cancer Network, Dose adjustment
forcytotoxics in renal impairment [internet]. accessed 12/01/2011
available at http://www.bopawebsite.org/tikidownload_file.php?fileId=620
Baxter K, editor. Stockleys Drug Interactions. Pharmaceutical Press;
2009. Accessed online on 06/05/09 available at
https://www.medicinescomplete.com/mc/
Allwood M, Stanley A, Wright P, editors. The cytotoxics handbook. 4th

Document Number
ASWCS11 GI022

Version Number

1.1.a

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Document title
Document number
Approval date
Written by
Checked by
Authorised by
Review date
Document reviewed by
Version number
Summary of changes

Controlled document

ed. Radcliffe Medical Press . 2002.


Summary of Product Characteristics Oxaliplatin Hospira 5mg/ml
concentration for solution for infusion (Hospira) [internet]. accessed
14/01/2011 available from
http://www.medicines.org.uk/EMC/medicine/20911/SPC
Summary of Product Characteristics Xeloda (Capecitabine)
500mg and 150mg Tablets (Roche) [internet], accessed
23/02/2011 available from
http://www.medicines.org.uk/EMC/medicine/4619/SPC/Xeloda/

XELOX/ CAPOX (Xeloda (Capecitabine) and Oxaliplatin)


ASWCS11 GI022
19/07/2011
Stephen Falk, Consultant Clinical
Oncologist BHOC
Digitally signed by James Carr
James Carr, Network Pharmacist,
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'
ASWCS
Digitally signed by Jeremy Braybrooke
Jeremy Braybrooke, Chair ASWCS
DN: cn=Jeremy Braybrooke, o, ou,
c=GB
Drugs and Therapeutics Committee Jeremy Braybrooke email=james.carr@aswcs.nhs.uk,
Date: 2011.07.27 15:11:41 +01'00'
19/07/2013

Steve Falk

James Carr

1.1.a
Version

Document Number
ASWCS11 GI022

Version Number

1.1.a

Page 6 of 6

Digitally signed by Steve Falk


DN: cn=Steve Falk, o, ou, email=james.carr@aswcs.nhs.
uk, c=GB
Date: 2011.07.27 15:10:45 +01'00'