Download Regimen : Bevacizumab for metastatic colorectal cancer ICD10

Regimen : Bevacizumab for metastatic colorectal cancer
ICD10 codes pre-fixed with: C18, C19, C20
Indications
First or second line treatment of advanced colorectal cancer, in
combination with irinotecan and fluoropyrimidine
First or second line treatment of advanced colorectal cancer, in
combination with oxaliplatin-based chemotherapy
Note: Patients with liver-only unresectable metastases should receive
cetuximab if k-ras wild type. Bevacizumab may be prescribed if k-ras
mutant.
This drug is only available through application to the NHS South
West Cancer Drugs Fund.
Exclusion Criteria
Regimen details
Administration
Contraindicated in patients who have a history of hypersensitivity
reaction to bevacizumab or other recombinant human or humanized
antibodies
Caution in patients with:
• Untreated central nervous system metastases
• Uncontrolled hypertension
• History or risk factors for thromboembolic events
• Significant cardiac risk factors for development of congestive
heart failure
Day
Drug
Dose
Route
1
Bevacziumab
5mg/kg
IV
(if given two weekly)*
OR
1
Bevacizumab (if given
7.5mg/kg
IV
three weekly)*
*The two weekly schedule is used with fluorouracil-based regimens
(FOLFOX, FOLFIRI); the three weekly schedule is used with the
capecitabine-based regimens (XELOX, XELIRI)
Bevacizumab is administered as an intravenous infusion, ensuring the
concentration of the diluted infusion solution is within the range 1.4 to
16.5mg/ml. Doses up to 1650mg are administered in 100ml sodium chloride
0.9%, doses greater than 1650mg are administered in 250ml sodium
chloride 0.9%.
The first infusion must be given over 90 minutes. If tolerated, the next
infusion can be given over 60 minutes; if this is also tolerated, subsequent
infusions can be given over 30 minutes.
Units administering bevacizumab must have facilities available for
resuscitation and the treatment of anaphylaxis.
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
Controlled document
Document Number
ASWCS12 GI028
Version Number
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re-started at a slower infusion rate. Chlorphenamine 10mg IV may be
administered.
Severe reactions, such as hypotension, dyspnoea, angioedema or
generalised urticaria require immediate discontinuation of bevacizumab
and appropriate therapy. Paracetamol can be used to treat reactions.
Frequency
Extravasation
Premedication
Emetogenicity
Additional
recommended
supportive
medication
Pre-treatment
evaluation
Bevacizumab therapy should not be initiated for at least 35 days
following major surgery or until the surgical wound is fully healed. If
elective surgery is planned, bevacizumab should be withheld for at least
35 days.
For minor surgery, including port placement, it is recommended that
bevacizumab is withheld for 7 days after surgery.
Every 14 or 21 days depending on chemotherapy regimen used (see
‘Regimen details’ above)
Neutral (Group 1)
None routinely. If a patient experiences a mild infusion related reaction, then
future doses can be given with Paracetamol 1gram PO and Chlorphenamine
10mg IV.
This regimen has low emetogenic potential – refer to local protocol
None usually required. Antihypertensives may be required to manage the
hypertension commonly observed with bevacizumab therapy.
FBC
U+E
LFT
Cardiac assessment
including history and physical
exam. ECHO is required in
patients who have had chest
wall radiation or prior
treatment with an
anthracycline.
Regular
investigations
Baseline – results valid for 28 days
Baseline – results valid for 28 days
Baseline – results valid for 28 days
Baseline – results valid for 28 days
Proteinuria (dipstick analysis)
Blood Pressure. Must be <
150/100mmHg.
Baseline – results valid for 72 hours
Baseline – results valid for 28 days
Blood Pressure
Perform prior to infusion on first day of
cycle 1. Monitor every 2-3 weeks or more
frequently in patients with hypertension
Proteinuria (dipstick analysis)
Standard limits for
administration to
go ahead – if blood
Before each dose; if 3+ on dipstick,
perform 24-hour urinalysis and delay
treatment until urine protein < 2g/24hrs.
None, unless specified by clinician in individual cases.
results not within range,
authorisation to administer
must be given by
prescriber/consultant
Dose
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Document Number
ASWCS12 GI028
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modifications
Haematological
toxicity
Renal
impairment
Hepatic
impairment
NCI Common
toxicity criteria
No dose reduction required.
There are no data for bevacizumab in patients with renal impairment but dose
adjustments should not be required since the kidneys are not a major route of
bevacizumab metabolism or excretion.
However, deteriorating organ function should be discussed with the consultant as
this may be a sign of disease progression.
There are no data for bevacizumab in patients with hepatic impairment but dose
adjustments should not be required since the liver is not a major route of
bevacizumab metabolism or excretion.
However, deteriorating organ function should be discussed with the consultant as
this may be a sign of disease progression.
Toxicity
Definition
Dose adjustment
Infusion-related
reactions
Grade ≤ 2
90-minute infusion: continue with
dose as normal but give premedications (e.g. paracetamol 1g
PO and chlorpheniramine 10mg IV)
with the next dose and give this over
90 minutes. If the next dose is well
tolerated, subsequent infusions may
be reduced by 30 minutes as long
as premedication is used.
60-minute infusion: all subsequent
doses should be given over 90
minutes (with pre-medication).
30-minute infusion: all subsequent
doses should be given over 60
minutes (with premedication).
Permanently discontinue
Asymptomatic transient (< 24 hrs)
increase by > 20 mmHg (diastolic) or
to > 140/90 mmHg if previously
within normal limits. Re-check BP 1
hour later:
(a) If BP <140/90mmHg: administer
as normal; no further action needed
Hypertension
Grade >2
Grade 1
Grade 2
Controlled document
Document Number
ASWCS12 GI028
(b) If BP 140/90mmHg –
150/100mmHg, administer
bevacizumab but re-check BP 48
hours later.
(c) If BP >150/100mmHg omit
bevacizumab and recheck BP 48
hours later.
For (b) and (c), commence
antihypertensive therapy if BP
remains >140/90mmHg
Recurrent or persistent (> 24 hr)
increase by 20 mmHg
(diastolic) or to > 140/90 mmHg if
previously within normal limits.
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Grade 3
Grade 4
Proteinuria
(on dipstick)
Adverse
effects – the
contents of the table
indicate the adverse
Controlled document
<2
≥2+
Nephrotic
syndrome
Anti-hypertensive therapy should be
commenced. Once controlled to
<140/90 mmHg, continue
bevacizumab therapy.
Requiring more than one antihypertensive or more intensive
therapy than previously.
Withhold bevacizumab for persistent
hypertension >140/90 mmHg.
If hypertension cannot be controlled,
permanently discontinue
bevacizumab.
Life threatening (e.g. hypertensive
crisis). This is a medical emergency.
Permanently discontinue
bevacizumab.
Continue with bevacizumab as normal
See algorithm below
Permanently discontinue
bevacizumab
Rare but serious side effects
Frequently occurring side effects
Arterial/venous thromboembolism
GI perforation, fistulas, wound
dehiscence
Infusion-associated symptoms /
acute hypersensitivity reactions
Document Number
ASWCS12 GI028
Version Number
0.3.a
Last printed 08/01/2013 11:45:00 * Only valid on day of printing
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effects that should
be documented on
consent to treatment
forms
Haemorrhage
Pulmonary haemorrhage/haemoptysis
Pneumonitis
Osteonecrosis of the jaw
Reversible posterior
leukoencephalopathy syndrome
Congestive heart failure
Other
No significant interactions.
Significant drug
interactions – For full details
Hypertension
Proteinuria
Headache
Fatigue
Diarrhoea
Nausea and vomiting
Abdominal pain
consult product literature/reference
texts
Comments
Cumulative Doses
References
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None
N/A
Hurwitz HI, Fehrenbacjer L, Hainsworth JD, Heim W, Berlin J, Holmgren E, et al.
Bevacizumab in combination with fluorouracil and leucovorin: an active regimen for firstline metastatic colorectal cancer. J Clin Oncol 2005; 23(15): 3502–3508.
Saltz LB, Clarke S, Diaz-Rubio E, Scheihauer W, Figer A, Wong R, et al. Bevacizumab
in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic
colorectal cancer: A randomized phase III study. J Clin Oncol 2008; 26 (12): 2013-2019.
Tyagi P and Grothey A. Commentary on a phase III trial of bevacizumab plus XELOX or
FOLFOX4 for first-line treatment of metastatic colorectal cancer: the NO16966 trial. Clin
Colorectal Cancer 2006; 6(4): 261-4.
Kabbinavar FF, Schulz J, McCleod M, Patel T, Hamm JT, Hecht JR, et al. Addition of
bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal
cancer: results of a randomized phase II trial. J Clin Oncol 2005; 23(16): 3697–3705.
Giantonio BJ, Catalano PJ, Meropol NJ, O’Dwyer PJ, Mitchell EP, Alberts SR, et al.
Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for
previously treated metastatic colorectal cancer: results from the Eastern Cooperative
Oncology Group Study E3200. J Clin Oncol. 2007; 25(12): 1539-44
Van Cutsem E, Rivera F, Berry S, Kretzschmar A, Michael M, DiBartolomeo M, et al.
Safety and efficacy of first-line bevacizumab with FOLFOX, XELOX, FOLFIRI and
fluoropyrimidines in metastatic colorectal cancer: the BEAT study. Ann Oncol 2009; 20
(11): 1842–1847.
Daniels S. North London Cancer Network, Dose adjustment for cytotoxics in hepatic
impairment [internet]. accessed 02/03/2012 available at
http://www.nlcn.nhs.uk/sites/default/files/pro_board_gu/2008/07/Hepatic%20impairment%20%20Dosage%20adjustment%20for%20cytotoxics.doc
Daniels S. North London Cancer Network, Dose adjustment for cytotoxics in renal
impairment [internet]. accessed 02/03/2012 available at
http://www.nlcn.nhs.uk/sites/default/files/pro_board_gu/2008/07/Renal%20impairment%20%
20-%20Dosage%20adjustment%20for%20cytotoxics.doc
Summary of Product Characteristics Avastin 25mg/ml concentrate for solution for infusion
(Roche) [internet]. accessed 27/02/2012 available from
http://www.medicines.org.uk/EMC/medicine/15748/SPC
North of England Cancer Network. Bevacizumab (Avastin) for Colorectal Cancer Protocol
[internet]. Accessed 27/02/2012 available from
http://www.cancernorth.nhs.uk/hpSite/groups/Networkcrosscuttinggroups/chemotherapy/colo
rectal
South East London Cancer Network. Bevacizumab protocol [internet]. Accessed
27/02/2012 available from
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Document Number
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Version Number
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Last printed 08/01/2013 11:45:00 * Only valid on day of printing
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•
http://www.selcn.nhs.uk/content/dynamic.asp?id=829&dynamic_id=88&subid=843
Surrey, West Sussex and Hampshire Cancer Network. Bevacizumab (Avastin)
[internet]. Accessed 27/02/2012 available from http://www.swshcn.nhs.uk/healthcareprofessionals/clinical-policies-and-protocols/oncology_protocols/healthcareprofessionals/clinical-policies-and-protocols/oncology_protocols/gastro-intestinalcancer/Colorectal%20Cancer/Bevacizumab%20V1%201.11.pdf
Document title
Document number
Approval date
Written by
Checked by
Authorised by
Review date
Document reviewed by
Version number
Summary of changes
Controlled document
Bevacizumab for colorectal cancer
ASWCS12 GI028
07/01/2013
Steve Falk, Consultant Clinical
Oncologist, BHOC
Georgina Holmes, Pharmacist,
UHBristol NHSFT
Jeremy Braybrooke, Chair ASWCS
Network Chemotherapy Group
07/01/2015
Version
Steve Falk
Georgina Holmes
Jeremy Braybrooke
0.3.a
Document Number
ASWCS12 GI028
Version Number
0.3.a
Last printed 08/01/2013 11:45:00 * Only valid on day of printing
Page 6 of 6
Digitally signed by Steve Falk
DN: cn=Steve Falk, o, ou, [email protected], c=GB
Date: 2013.01.08 11:46:29 Z
Digitally signed by Georgina Holmes
DN: cn=Georgina Holmes, o=NHS, ou=NHS,
[email protected], c=GB
Date: 2013.01.08 11:46:45 Z
Digitally signed by Jeremy Braybrooke
DN: cn=Jeremy Braybrooke, o, ou,
[email protected], c=GB
Date: 2013.01.08 11:47:04 Z