CAPIRI (XELIRI or Irinotecan & Capecitabine)

DRUG ADMINISTRATION SCHEDULE

Day Drug Dose Route Diluent &Rate
Glucose 5% 500ml Infusion Fast Running / Line Flush
Ondansetron 8mg Oral /Slow bolus/15 min infusion
Day 1
Dexamethasone 8mg IV bolus Via Glucose drip
250ml Glucose 5%
Irinotecan 200mg/m2 IV Infusion
over 2 hours
Days 1 800 mg/m2
Capecitabine Oral N/A
to 14 twice a day
*Ondansetron IV must be infused over 15 minutes in patients over 65 years of age.

PREMEDICATION
*If acute cholinergic syndrome appears atropine sulphate 250micrograms should be
administered by subcutaneous injection unless clinically contraindicated.
The manufacturer recommends the use of prophylactic atropine sulphate with subsequent
doses of irinotecan.

DOSE FORM
Capecitabine available as 500mg and 150mg tablets.

CYCLE LENGTH AND NUMBER OF DAYS

Treatment administered every 21 days, usually for up to 8 cycles.

APPROVED INDICATIONS
Treatment of Advanced Colorectal Cancer, in patients who would otherwise be considered
for Irinotecan-MdG (FOLFIRI).

ELIGIABILITY CRITERIA
Colorectal cancer patients with adequate renal function.

EXCLUSION CRITERIA
 Patients with baseline renal function less than 30 ml/min.
 Patients incapable of managing oral chemotherapy themselves or with the assistance
of a carer
 Patients with swallowing difficulties

RECOMMENDED TAKE HOME MEDICATION

Ondansetron 8mg twice daily for 2 days
Dexamethasone 4mg twice daily for 1 day
Metoclopramide 10mg three times daily as required
Loperamide as required (4mg after first loose stool and 2mgs every 2 hours, to a
maximum of 16 (2mg) tablets in 24 hours.
For diarrhoea lasting greater than 24 hours give ciprofloxacin 250mg BD.

INVESTIGATIONS / MONITORING REQUIRED

FBC, U&E’s, LFT’s & tumour markers as appropriate prior to each course of chemotherapy
FBC on the day of chemotherapy
Where CEA is elevated this should be measured before each cycle.

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ASSESSMENT OF RESPONSE
Assessed radiologically after 4th cycle.
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
 Irinotecan must only be given in units where clear arrangements are made to manage
possible toxicity related out of hour's admissions. Patients must be made aware of the
risk of delayed diarrhoea occurring 24 hours after the administration of Irinotecan and
at any time before the next cycle. This means supplying information sheets to the
patient and if appropriate to their GP.
 Early onset diarrhoea (within the first 24 hours). Can be a result of acute cholinergic
syndrome and may occur in 9% of patients. Symptoms are short lasting and respond
within minutes to administration of atropine (0.25-1mg subcutaneously)
 Delayed diarrhoea must be treated immediately with high dose Loperamide (4mg after
first loose stool and 2mgs every 2 hours, to a maximum of 16 (2mg) tablets in 24 hours.
Hospitalise if condition not resolved in 48 hours.
 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
 Acute cholinergic syndrome (defined as early diarrhoea and various other symptoms
such as sweating, abdominal cramping, lacrimation, myosis and salivation)
 Diarrhoea –risk of severe delayed diarrhoea – can be life threatening
 Nausea and Vomiting
 Stomatitis
 Palmar/Plantar Erythrodysesthesia (PPE) - Can be severe, patients must be
forewarned
 Pyrexia, fatigue, asthenia, anorexia
 Myelosuppression
 Hyperbilirubinemia
 Cardiotoxicity - Occasionally patients may experience coronary artery spasm. Stop
Treatment with fluoropyrimidine therapy if this occurs.

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 CAPIRI (XELIRI or Irinotecan & Capecitabine)
DPD Deficiency and Severe Toxicity Risk
Dihydropyrimidine dehydrogenase (DPD) plays an important role in the metabolism of
fluoropyrimidine drugs 5-fluorouracil (5FU) and capecitabine. Patients with DPD deficiency may
be predisposed to experience increased or severe toxicity when receiving 5-FU or
capecitabine, and in some cases these events can be fatal.
For all patients having capecitabine or fluorouracil, the risk of severe side effects from
capecitabine or 5FU if patients have a deficiency of DPD must be mentioned and patient
given a copy of the DPD toxicity information leaflet from cancer research UK.
Available At http://www.cancerresearchuk.org/about-cancer/cancer-in-
general/treatment/chemotherapy/side-effects/dpd-deficiency-and-fluorouracil

EXTRAVASATION See NCA / local Policy

DOSE MODIFICATION / TREATMENT DELAYS Haematological toxicity:

 Discuss with consultant if ANC 1 to 1.5 and/ or Platelets < 75 to 100.
 Delay 1 week if ANC < 1 and/or PLTs < 75.
 No dose reduction for CTC grade I/II ANC
 Grade III/IV ANC → delay chemotherapy until recovered, then proceed at 20%
capecitabine and Irinotecan dose reduction
 If further delay(s) for bone marrow suppression occur despite a 20% dose reduction,
consider a further 20% dose reduction.

Non-haematological toxicity:
Diarrhoea
Grade 1 (watery stool 2-3 times/day)
Grade 2 (watery stool 4-6 times/day)
Grade 3/4 (watery stool >7 times/day)
Loperamide 4mg then 2mg QDS PRN.
Delay treatment until recovered and give full
dose
Delay until recovered and resume treatment
at 25% reduced dose of oxaliplatin and
irinotecan

Table of dose adjustments according to CTC toxicity (Not PPE/hand/foot syndrome)

Grade 2 Grade 3 Grade 4
Interrupt treatment until Interrupt treatment until
resolved to grade 0/1, then resolved to grade 0/1, then
Discontinue
1st appearance continue at 100% of original continue at 75% of original
treatment
dose with prophylaxis where dose with prophylaxis
possible where possible
Interrupt treatment until Interrupt treatment until
resolved to grade 0/1, then resolved to grade 0/1, then
2nd appearance
continue at 75% of original continue at 50% of original
dose dose
Interrupt treatment until
resolved to grade 0/1, then
3rd appearance Discontinue treatment
continue at 50% of original
dose
4th appearance Discontinue treatment

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 CAPIRI (XELIRI or Irinotecan & Capecitabine)
Once the capecitabine dose has been reduced, it should not be increased at a later time.
Omitted doses are not replaced or restored, instead the patient should resume the
planned treatment cycle.

Table of PPE (hand/foot syndrome) toxicity grading for capecitabine only

Grade Clinical Functional Management
Numbness, Discomfort but no interruption
1
dysesthesia/parathesi of normal activities
a, tingling,
Painful painless
erythema with Discomfort which affects Interrupt treatment
2
swelling or erythema activities of daily living until grade ≤1
Moist desquamation, Severe discomfort, unable to Interrupt treatment
3 ulceration, Blistering, work or perform activities of until grade ≤1 and
severe pain daily living reduce dose by 25%

Once the capecitabine dose has been reduced, it should not be increased at a later time.
Omitted doses are not replaced or restored, instead the patient should resume the
planned treatment cycle.

Hepatic impairment
Administration of capecitabine should be interrupted if treatment-related elevations in
bilirubin of > 3.0 x ULN or treatment-related elevations in hepatic aminotransferases (ALT,
AST) of > 2.5 x ULN occur. Treatment with capecitabine monotherapy may be resumed
when bilirubin decreases to ≤ 3.0 x ULN or hepatic aminotransferases decrease to ≤ 2.5 x
ULN.

Renal function
GFR Capecitabine Oxaliplatin
30-50 ml/min 25% dose reduction No action
< 30 ml/min Contact prescriber Contact prescriber

REFERENCES:
1. Reinacher-Schick AC et al. Activity of the combination of bevacizumab (Bev) with
capecitabine/irinotecan (CapIri/Bev) or capecitabine/oxaliplatin (CapOx/Bev) in
advanced colorectal cancer (ACRC): a randomized phase II study of the AIO Colorecal
Study Group (AIO trial 0604). Am Soc Clin Oncol 2008; Abstract 4030
2. Koopman M et al. Sequential versus combination chemotherapy with capecitabine,
irinotecan, and oxaliplatin in advanced colorectal cancer (CAIRO): a phase III
randomised controlled trial. Lancet 2007; 370: 135-42
3. Ducreux M et al. Efficacy and safety of bevacizumab (BEV)-based combination
regimens in patients with metastatic colorectal cancer (mCRC): Randomised phase II
study of BEV + FOLFIRI versus BEV + XELIRI (FNCLCC ACCORD13/0503 study). Am
Soc Clin Oncol, Annual Meeting 2009; Abstract 4086 and associated oral presentation

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 CAPIRI (XELIRI or Irinotecan & Capecitabine)
Document Control
Document Title: CAPIRI-XELIRI CNTW protocol CRP09 CR017
Current
Document No: CRP09 CR017 1.4
Version:
Chris Beck Chemotherapy Pharmacist Date
Reviewer: 28.02.18
Northern Cancer Alliance Approved:
Steve Williamson Consultant Due for
Approved by: 01.03.21
Pharmacist Northern Cancer Alliance Review
Summary of
1.1 Amended inconsistencies in dose adjustment advice, updated toxicities list.
Changes
1.2 Protocol reviewed. Volume of Irinotecan infusion amended.

1.3 Protocol reviewed and reissued, Antiemetic advice updated

1.4 Protocol reviewed, parameters updated from Chemocare. DPD toxicity advice added

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Issue Date 28.02.18 Expiry Date: 01.03.2021