Download AFLIBERCEPT (ZALTRAP®) PROTOCOL

AFLIBERCEPT (ZALTRAP®) PROTOCOL
Cumbria, Northumberland, Tyne & Wear
Area Team
Aflibercept (Zaltrap®) for the second line treatment of
metastatic colorectal cancer
DRUG ADMINISTRATION
Day
Drug
Daily Dose
Route
Day 1
Aflibercept
4 mg/kg
Infusion
Diluent & Rate
100mls Normal Saline
Over 60 minutes
DOSE FREQUENCY
To be given every two weeks with two weekly FOLFIRI until disease progression or
unacceptable toxicity. Aflibercept should be administered before chemotherapy.
WARNING: MUST USE THIS PROTOCOL IN CONJUNCTION WITH IRINOTECAN
COMBINATION REGIMEN PROTOCOL
APPROVED INDICATIONS
Approved for use on the National Cancer drugs 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. PS 0-2
4. Progression following first line treatment with oxaliplatin based combination
chemotherapy with or without Bevacizumab
5. Given in combination with irinotecan-based combination chemotherapy until
unacceptable toxicity or disease progression
Note: Aflibercept is only approved for use in combination with irinotecan based
chemotherapy and is not approved as a single agent maintenance therapy
PREMEDICATION
Anti-emetics are not required for Aflibercept treatment
Take home medications as per Irinotecan chemotherapy regimen ‘backbone’
INVESTIGATIONS / MONITORING REQUIRED
Chemotherapy
 Prior to each cycle - FBC, U/Es, LFTs as required per protocol
Aflibercept
 Blood pressure before each dose
 Urinalysis for proteinuria before each dose
Aflibercept colorectal cancer NCDF Regimen v1.1
Issued 11 Feb 2014
Page 1 of 3
Expiry Date: 11 Feb 2016
AFLIBERCEPT (ZALTRAP®) PROTOCOL
Cumbria, Northumberland, Tyne & Wear
Area Team
REVIEW BY CLINICIAN
Review at each cycle as appropriate
NURSE / PHARMACIST LED REVIEW
Each cycle as applicable according to local protocols
ADMINISTRATION NOTES
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All does administered in 100ml sodium chloride 0.9% as an intravenous infusion
over 60 minutes via a PVC-free giving set with a 0.2 micron in – line filter (final
concentration 0.6-8mg/ml).
If a patient experiences a mild to moderate infusion-related reaction, pretreatment with hydrocortisone and chlorphenamine may be considered with
subsequent doses. Aflibercept must be discontinued after a severe reaction.
Aflibercept may adversely affect the wound healing process. Therapy should be
withheld for 4 weeks prior to elective surgery.
For minor surgery, including port placement, it is recommended that aflibercept is
withheld for 7 days after surgery.
Pre-existing hypertension should be adequately controlled (usually bu GP) before
starting aflibercept treatment.
Note: No treatment breaks of more than 4 weeks beyond the expected treatment
break are allowed (to allow any toxicity of current therapy to settle or in the case
of intercurrent co-morbidities).
If a treatment break of more than 4 weeks is required, i.e. surgery with prolonged
recover time, then an Individual Funding Request will need to be submitted, as
per CDF processes.
EXTRAVASATION Follow Network and Local Trust Guidelines
MAIN TOXICITIES
 Infusion-related reactions
 Gastrointestinal perforations and fistulae (serious but rare)
 Haemorrhage and delayed wound healing
 Hypertension
 Proteinuria
 Increased risk of diarrhoea
 Arterial thromboembolism and increased risk of DVT
DOSE MODIFICATIONS
Hepatic Impairment:
Dose adjustment is not required for mild to moderate hepatic impairment. There are
no data for aflibercept use in severe renal impairment.
Hypertension
 Baseline blood pressure should be < 150/100mmHg.
 A suggested assessment of blood pressure results is:
 If diastolic increase > 20mmHg above baseline or blood pressure rises to >
150/100mmHg, antihypertensive therapy may be required.
 If blood pressure > 180/110mmHg, it is advised that Aflibercept therapy is
withheld until blood pressure is well controlled.
Aflibercept colorectal cancer NCDF Regimen v1.1
Issued 11 Feb 2014
Page 2 of 3
Expiry Date: 11 Feb 2016
AFLIBERCEPT (ZALTRAP®) PROTOCOL

Cumbria, Northumberland, Tyne & Wear
Area Team
If there are recurrent problems with sever hypertension, Aflibercept should be
suspended until controlled and then the dose reduced to 2mg/kg for all
subsequent doses.
Proteinuria:
 A suggested assessment of urine dipstick results is:
 1+ or 2+ on dipstic (0.3 -2.9g/l): continue with aflibercept. No additional
evaluation required.
 3+ on dipstick (3 – 19g/L): may have dose of aflibercept as scheduled, but will
need 24 hour urine to measure 24 hour protein to be done a few days before next
cycle is due.
 If 24 hr protein result < 2g, continue with aflibercept, with continued proteinuria
monitoring via 24 hour urine before each dose. If the 24 hour protein level falls to
< 1g/24hr, return to dipstick analysis.
 If ≥ 2g, withhold aflibercept until repreat 24 hour urine collection shows < 2g
protein. Then re-introduce aflibercept, with continued proteinuria monitoring via
24 hour urine.
 If recurrence of ≥ 2g, withhold aflibercept again until <2g protein per 24 hours,
and then give 2mg/kg aflibercept for subsequent doses.
 4+ on dipstick (≥ 20g/L): withhold aflibercept. 24-hour urine required. Follow 24
hour urine monitoring and guidance as for 3+ on dipstick.
 Note: There is very limited data available for aflibercept in severe renal
impairment , so these patients should be treated with extra caution.
REFERENCES
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Van Cutsem E., et al. Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a
phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin
based regimen. J Clin Oncol. 2012 Oct 1;30(28):3499. 506. Epub 2012 Sep 4
Aflibercept summary of product characteristics (SPC). Available at
http://www.medicines.org.uk/emc/medicine/27413/SPC/Zaltrap+25mg+ml+concentrate+for+solution+for+infu
sion Last accessed 13.02.14
TREATMENT LOCATION
Cancer Centre or Cancer Unit where there is an Oncologist with a specialisation in
Colorectal cancer patients as appropriate.
Document Title:
Aflibercept colorectal cancer NCDF Regimen v1.1
Document No:
NCDF02
Prepared By:
Approved by:
Mandy Nagra
NHS England CNTW Area
Team
Steve Williamson
Consultant Cancer Pharmacist
Current Version:
1.1
Date
Approved:
20.02.14
st
Due for Review:
1 March 2016
Summary of
Changes
V1.1
Document approved.
Aflibercept colorectal cancer NCDF Regimen v1.1
Issued 11 Feb 2014
Page 3 of 3
Expiry Date: 11 Feb 2016