Download FEC/T

Regimen: Fluorouracil, Epirubicin and Cyclophosphamide + Docetaxel (FEC/T)
for Early Breast Cancer
Indication
Adjuvant treatment for node positive early breast cancer
This protocol is subject to local approval
Regimen detail
Administration
Cycles 1 - 3
Day Drug
1
Fluorouracil (5-FU)
1
Epirubicin
1
Cyclophosphamide
Cycles 4 - 6
1
Docetaxel
Dose
500mg/m2
100mg/m2
500mg/m2
Route
IV
IV
IV
100mg/m2
IV
G-CSF: give one of the following agents (according to local
policy). Primary prophylaxis with GCSF is recommended.
2-6
Filgrastim
≤60kg = 300μg od
SC
>60kg = 480μg od
†
2-6
Lenograstim
≤1.75m2 = 263μg od
SC
>1.75 m2 = 150μg/m2
†
od
2‡
Pegfilgrastim
6mg stat
SC
®
(Neulasta )
Fluorouracil, epirubicin and cyclophosphamide are administered by slow
intravenous bolus in to the side arm of a fast flowing drip of 0.9% sodium
chloride.
Cyclophosphamide may be given in 250-500ml 0.9% sodium chloride
over 30 minutes.
Docetaxel is administered in a 250ml PVC-free sodium chloride 0.9% bag
over 60 minutes. Doses >190mg should be diluted in 500ml (maximum
concentration 0.74mg/ml).
Patients should be observed closely for hypersensitivity reactions,
particularly during the docetaxel infusions. Hypersensitivity reactions may
occur within a few minutes following the initiation of the infusion of
docetaxel and, therefore, 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. Severe reactions, such as
hypotension, bronchospasm or generalised rash/erythema require
immediate discontinuation of docetaxel and appropriate therapy. Patients
who have developed severe hypersensitivity reactions should not be re-
Controlled document
Document No
Version Number
ASWCS09 BR015
1.1.a
Last printed 03/12/2010 11:52:00 *ONLY VALID ON DATE OF PRINTING*
Page 1 of 5
challenged with docetaxel.
Frequency
Every 21 days
6 cycles (maximum)
Extravasation
Fluorouracil is an inflammatant (Group 2)
Epirubicin is a vesicant (Group 5)
Cyclophosphamide is a neutral agent (Group 1)
Docetaxel is an exfoliant (Group 4)
None required for FEC
Docetaxel - Dexamethasone 8mg bd PO for 3 days, starting the day
before each cycle of chemotherapy. Patient should receive 3 doses prior
to treatment. In the case where 3 doses have not been taken,
dexamethasone 20mg IV should be administered 30-60 minutes prior to
chemotherapy and the remaining 3 oral doses should be administered as
per standard.
Premedication
Emetogenicity
Additional recommended
supportive medication
FEC: This regimen has moderate-high emetic potential – refer to local
protocol
Docetaxel: This regimen has moderate-low emetic potential – refer to
local protocol
Mouthwashes as per local policy
H2 antagonist or Proton Pump Inhibitor if required
Loperamide 4mg po stat then 2mg prn if diarrhoea develops
Pre- treatment
evaluation
FBC
LFT
U&E (inc. SrCr)
ECHO or
MUGA
Baseline - results valid for 28 days
Baseline - results valid for 28 days
Baseline - results valid for 28 days
Baseline if significant cardiac history or previous
anthracycline therapy, repeated if suspicion of cardiac
toxicity or as necessary
Regular investigation
FBC
LFT
U&E (inc. SrCr)
Clinical
Assessment
Pre D1 – results valid for 72 hours
Pre D1 – results valid for 7 days
Pre D1 – results valid for 7 days
Clinically assess patient prior to each cycle,
particularly focusing on whether the patient has
developed stomatitis, cardiotoxicity or local toxicity.
Ask about neuropathy when patients are on docetaxel.
Standard limits for
administration to go
ahead – if blood results not
within range, authorisation to
administer must be given by
prescriber/consultant
Dose modifications
•
Haematological
toxicity
Controlled document
Neutrophil count
≥ 1 x 109/l
Platelet count
≥100 x 109/l
Creatinine Clearance
> 50ml/min*
Bilirubin
<1.5 x ULN
ALT +/- Alk Phos
<2.5 x ULN
* During FEC only
Use lower dose of epirubicin (75 or 60mg/m2) for patients with significant
co-morbidity
Delay 1 week if neutrophils <1.0 x 109/l and/or platelets <100 x 109/l.
20% dose reduction should be considered if myelosuppression results in
Document No
Version Number
ASWCS09 BR015
1.1.a
Last printed 03/12/2010 11:52:00 *ONLY VALID ON DATE OF PRINTING*
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delay of subsequent courses.
In adjuvant treatment, dose reduction and delays can compromise
outcome. G-CSF should be considered if more than one delay and/or
before dose reduction. Contact relevant consultant.
•
Renal
impairment
CrCl (ml/min)
> 20
10-20
<10
•
Hepatic
impairment
Fluorouracil
dose
100%
100%
Consider dose
reduction
Epirubicin
dose
100%
100%
Consider dose
reduction
Cyclophosphamide
dose
100%
75%
50%
No modifications of docetaxel dose for unless severe renal impairment
(<10ml/min)
FEC
Bilirubin
ALT / Alk
phos
Fluorouracil
(5FU) dose
Epirubicin
dose
Cyclophosphamide
dose
1.5-3 x
ULN
3-5 x
ULN
>5 x
ULN
2.5 – 5 x
ULN
5 – 10 x
ULN
> 10 x
ULN
100%
50%
100%*
Omit
25%
100%*
Omit
Omit
Consider dose
reduction / use
alternative regimen*
* Cyclophosphamide is not recommended in patients if bilirubin > 1.5 x
ULN or AST/ALT >2–3xULN, but exposure to active metabolites may
not be increased and therefore a dose reduction may not be necessary.
Consultant decision.
Docetaxel
AST +/or ALT
Alk Phos*
Docetaxel dose
< 1.5 x ULN and < 2.5 x ULN
100%
2.5 – 3.5 x ULN 2.5 - 6 x ULN 1
75%
and
> 3.5 x ULN
6– 10 x ULN and
60% (Discuss with consultant)
*If Bilirubin > 1.5 x ULN, withhold dose. Consultant decision to treat.
•
NCI Common
Toxicity Criteria
Toxicity
Febrile
neutropenia
Definition
ANC <0.5 x 109/l
plus fever requiring
IV antibiotics +/hospitalisation
Stomatitis & for Grade III painful
Mucositis
erythema or ulcers
requiring
rehydration
resolving to Grade I
or less by day 21
Other
Grade III/IV toxicity
toxicities
(except alopecia)
Controlled document
Dose adjustment
Consider G-CSF for subsequent
cycles or 20% reduction of
epirubicin and cyclophosphamide or
docetaxel if applicable
20% reduction of epirubicin and
fluorouracil
20% reduction of docetaxel if
applicable
Continue with 20% dose reduction
of suspected causative agent(s)
provided toxicity has resolved to
Grade I or less
Document No
Version Number
ASWCS09 BR015
1.1.a
Last printed 03/12/2010 11:52:00 *ONLY VALID ON DATE OF PRINTING*
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If further toxicity occurs, an
additional reduction may be made
after discussion with consultant.
• Defer treatment for any grade III/IV non-haematological toxicity
(excluding alopecia)
• If a delay of more than 3 weeks is required for recovery, or more than
2 dose reductions are necessary, the patient should discontinue
treatment
Adverse effects – the
contents of the table indicate
the adverse effects that should
be documented on consent to
treatment forms
Rare or Serious Side Effects
Febrile neutropenia
Myelosuppression
Risk of second malignancy e.g.
leukaemia
Cardiac toxicity
Teratogenicity
Long term risk of early
menopause, reduced fertility
Peripheral neuropathy
Frequently occurring Side Effects
Nausea and vomiting
Alopecia
Stomatitis and mucositis
Sore veins (Phlebitis)
Diarrhoea or constipation
Fatigue
Other side effects include: loss of appetite, taste disturbance, red urine for
24 hours post epirubicin, skin sensitivity, nail ridges, gritty eyes, blurred
vision, bladder irritation (including haemorrhagic cystitis), altered liver
function, myalgia.
Significant drug
interactions –
For full details consult product
literature/ reference texts
Comments
Co-trimoxazole/trimethoprim – Avoid if possible – enhances antifolate
effect. If essential, monitor FBC regularly
Enzyme inducers/inhibitors - in vitro studies suggest that CYP3A
inhibitors (such as ketoconazole and erythromycin) will raise docetaxel
levels, whereas CYP3A inducers (such as rifampicin and barbiturates) will
reduce docetaxel levels.
Dihydropyrimidine dehydrogenase (DPD) deficiency can result in severe
toxicity secondary to reduced fluorouracil metabolism – avoid use in
patients with known DPD deficiency
Cardiotoxicity has been associated with both anthracycline and
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.
Trastuzumab may be administered concurrently with docetaxel for patients
with HER2 positive breast cancer
Offer scalp cooling (cold capping) to appropriate patients
Cumulative Doses
Epirubicin has a life time maximum cumulative dose of 900mg/m2
References
• Roche H, Fumoleau P, Spielmann M, Canon J-L, Delozier T, Serin D,et
al; Sequential adjuvant epirubicin-based and docetaxel chemotherapy
for Node-positive breast cancer patients: The FNCLCC PACS 01 trial. J
Clin Oncol 2006, 24;5664-5671.
• Daniels S. North London Cancer Network, Dose adjustment for
Controlled document
Document No
Version Number
ASWCS09 BR015
1.1.a
Last printed 03/12/2010 11:52:00 *ONLY VALID ON DATE OF PRINTING*
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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
cytotoxics in hepatic impairment [internet]. accessed 16/04/2009
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 16/04/2009
available at http://www.bopawebsite.org/tikidownload_file.php?fileId=620
Baxter K, editor. Stockley’s Drug Interactions. Pharmaceutical Press;
2009. Accessed online on 06/05/09 available at
https://www.medicinescomplete.com/mc/
Trissel LA. Handbook of Injectable Drugs, 15th ed. American Society for
Health-Systems Pharmacists 2009. Accessed online on 06/05/09
available at http://www.medicinescomplete.com/mc/hid/current/
Allwood M, Stanley A, Wright P, editors. The cytotoxics handbook. 4th
ed. Radcliffe Medical Press . 2002.
Summary of Product Characteristics Fluorouracil 50mg/ml injection
(Hospira) [internet]. accessed 11/11/2009 available from
http://emc.medicines.org.uk/document.aspx?documentId=636
Summary of Product Characteristics Epirubicin Hydrochoride 2mg/ml
injection (Hospira) [internet] accessed 11/11/2009 available from
http://emc.medicines.org.uk/document.aspx?documentId=18609
Summary of Product Characteristics Cyclophosphamide 500mg
injection (Baxter) [internet]. accessed 11/11/2009 available from
http://www.ecomm.baxter.com/ecatalog/loadResource.do?bid =44228
Summary of Product Characteristics Taxotere®(Docetaxel) 20mg and
80mg concentrate and solvent for infusion (Sanofi Aventis)
[internet].accessed 21/05/2009 available from
http://emc.medicines.org.uk/document.aspx?documentId=4594
Summary of Product Characteristics Taxotere®(Docetaxel) 20 mg/1ml
and 80mg/4ml and 160 mg/8ml concentrate for solution for infusion
(Sanofi Aventis) [internet]. Accessed 01/09/2010 available from
http://www.medicines.org.uk/EMC/medicine/23210
FEC/T chemotherapy for breast cancer
ASWCS09 BR015
15/10/2010
Jeremy Braybrooke, Consultant Medical Oncologist,
BHOC, and Chair, ASWCS Drugs and Therapeutics
Committee
Becky Bagnall, Consultant Pharmacist, NBT
Jeremy Braybrooke, Chair ASWCS Drugs and
Therapeutics Committee
15/10/2011
Jeremy
Braybrooke
Digitally signed by Jeremy Braybrooke
DN: cn=Jeremy Braybrooke, o, ou,
[email protected], c=GB
Date: 2010.12.03 11:53:33 Z
Becky Bagnall
Jeremy
Braybrooke
Digitally signed by Becky Bagnall
DN: cn=Becky Bagnall, o, ou, email=james.carr@aswcs.
nhs.uk, c=GB
Date: 2010.12.03 11:52:55 Z
Digitally signed by Jeremy Braybrooke
DN: cn=Jeremy Braybrooke, o, ou,
[email protected], c=GB
Date: 2010.12.03 11:54:02 Z
1.1.a
Version
Document No
Version Number
ASWCS09 BR015
1.1.a
Last printed 03/12/2010 11:52:00 *ONLY VALID ON DATE OF PRINTING*
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