Download Regimen: Docetaxel, Carboplatin and Trastuzumab (TCH i.e.

Regimen:
Docetaxel, Carboplatin and Trastuzumab (TCH i.e. Taxotere®
Carboplatin, Herceptin®)
for Early Breast Cancer
Indication
Regimen details
Administration
Approved for the treatment of early and locally advanced breast cancer in
patients with lymph node positive, HER2 positive breast cancer where an
anthracycline is contra-indicated.
Day Drug
Dose
Route
1
Docetaxel
75mg/m2
IV
1
Carboplatin
AUC6
IV
1
Trastuzumab*
8mg/kg
IV
loading then
6mg/kg
*See protocol ASWCS10 BR018 (adjuvant trastuzumab) for monitoring
guidelines.
Order of administration: trastuzumab first, docetaxel second, carboplatin
third.
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).
Carboplatin is administered in 500ml 5% dextrose (or 0.9% sodium
chloride) over 60 minutes.
Avoid any device containing aluminium that may come into contact with
Carboplatin.
Frequency
Controlled document
Patients should be observed closely for hypersensitivity reactions,
particularly during the first and second infusions.
Hypersensitivity reactions may occur within a few minutes following the
initiation of the infusion of docetaxel, carboplatin or trastuzumab.
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 docetaxel and appropriate therapy. Patients who have
developed severe hypersensitivity reactions should not be re-challenged
with docetaxel.
Every 21 days
6 cycles chemotherapy
18 cycles of Trastuzumab
Document No
Version Number
ASWCS10 BR021
1.1.a
Last printed 19/01/2011 *ONLY VALID ON DATE OF PRINTING*
Page 1 of 5
Premedication
Docetaxel is an exfoliant (Group 4)
Carboplatin is an irritant (Group 3)
Trastuzumab is neutral (Group 1)
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 16 20mg IV should be administered 30-60 minutes prior to chemotherapy
and the remaining 3 oral doses should be administered as per standard.
Emetogenicity
This regimen has moderate-high emetic potential – refer to local protocol
Additional recommended
supportive medication
Mouthwashes as per local policy
H2 antagonist or Proton Pump Inhibitor if required
Consider GCSF if patients develop febrile neutropenia
Give diclofenac 50mg tds from Days 1-5 if the patient develops
myalgia/arthralgia. Prednisolone 5-10mg od from Days 2-6 and/or
gabapentin 300mg stat Day 0, 300mg bd Day 1 & 300mg tds Days 2-7
are alternative agents to use if myalgia/arthralgia persists
ECHO*
Pre-treatment and subsequent monitoring of cardiac
function is required. It is recommended that this
follows UK guidelines with an echocardiogram pre
chemotherapy and at 4 and 8 months. Further
assessment after completion of trastuzumab is
recommended for patients requiring cardiovascular
intervention.
FBC
Baseline - results valid for 28days
LFT
Baseline - results valid for 28 days
U&E (inc. SrCr) Baseline - results valid for 28 days
*or MUGA scan may be used according to local practice
Extravasation
Pre- treatment evaluation
Regular investigation
ECHO
Standard limits for
administration to go
ahead – if blood results not
Neutrophil count
Platelet count
Bilirubin
ALT +/- Alk Phos
within range, authorisation to
administer must be given by
prescriber/consultant
At 4 months and 8 months (more frequently only if
clinically indicated)
FBC
Pre D1 – results valid for 72 hours
LFT
Pre D1 – results valid for 7 days
U&E (inc. SrCr) Pre D1 – results valid for 7 days
Clinical
Clinically assess patient prior to each cycle,
Assessment
particularly focusing on whether the patient has
developed marked fatigue, neurological,
gastrointestinal, hypersensitivity, cutaneous or
oedematous symptoms.
≥1.0 x 109/l
≥100 x 109/l
≤1.5 x ULN
≤1.5 x ULN
Dose modifications
•
Cardiac Toxicity
See protocol ASWCS10 BR018 (adjuvant trastuzumab) for monitoring
guidelines.
•
Haematological
toxicity
Day 1: If neutrophils <1.0 x 109/l and/or platelets <100 x 109/l delay 1
week or until recovery.
Controlled document
Document No
Version Number
ASWCS10 BR021
1.1.a
Last printed 19/01/2011 *ONLY VALID ON DATE OF PRINTING*
Page 2 of 5
•
Renal impairment
•
Hepatic
impairment
•
NCI Common
Toxicity Criteria
Trastuzumab: no modifications required.
Docetaxel : no modifications required. Discuss with consultant if severe
renal impairment (CrCl < 10ml/min)
Carboplatin:
GFR ml/min
Carboplatin dose
>30
Use AUC as per protocol
≤30 calculated
EDTA then use AUC as per
protocol
≤30 EDTA
Discuss with consultant
AST +/or ALT
< 1.5 x ULN and
1.5 – 3.5 x ULN
and
> 3.5 x ULN and
Other toxicities
Controlled document
Docetaxel Dose
100%
75%
Not recommended.
Discuss with
consultant
†
Unless due to bone metastases only
If Bilirubin > 1.5 x ULN, docetaxel should usually be withheld. Consultant
decision to treat.
Carboplatin and Trastuzumab do not normally require dose reductions in
hepatic impairment.
Toxicity
Definition
Dose adjustment
Febrile
ANC <0.5 x 109/l
1st episode reduce docetaxel
neutropenia
plus fever requiring to 75% dose and carboplatin
IV antibiotics +/to AUC5. Consider
hospitalisation
prophylactic GCSF for
subsequent cycles.
2nd episode reduce docetaxel
to 60% dose and carboplatin
to AUC4
Peripheral
Grade 2
Reduce docetaxel to 75%
neuropathy
dose
Diarrhoea or
stomatitis
Adverse effects – the
contents of the table indicate the
adverse effects that should be
documented on consent to
treatment forms
Alk Phos†
< 2.5 x ULN
2.5 - 6 x
ULN
6 – 10 x
ULN
≥ grade 3
≥ grade 3
≥ grade 3 toxicity
(except alopecia)
Rare or Serious Side Effects
Febrile neutropenia
Myelosuppression
Risk of second malignancy e.g.
leukaemia
Infusion related reaction
Teratogenicity
Long term risk of early
menopause, reduced fertility
Discuss with consultant
1st episode reduce docetaxel
to 75%
2nd episode reduce docetaxel
to 60%
Defer therapy for 1 week until
resolved to ≤ grade 1. Discuss
with consultant if >1 week
delay
Frequently occurring Side Effects
Nausea and vomiting
Alopecia
Stomatitis and mucositis
Diarrhoea
Fatigue
Sore veins (phlebitis)
Document No
Version Number
ASWCS10 BR021
1.1.a
Last printed 19/01/2011 *ONLY VALID ON DATE OF PRINTING*
Page 3 of 5
Cardiac Toxicity
Other side effects include: myalgia, fluid retention, skin
sensitivity/changes, nail ridges and nail loss, altered liver function.
Significant drug
interactions –
For full details consult product
literature/ reference texts
Docetaxel: concomitant administration of substrates, inducers or
inhibitors of CYP-3A e.g. ciclosporin, terfenadine, ketoconazole,
erythromycin, rifampicin, barbiturates etc, may alter the pharmacokinetics
of docetaxel
Carboplatin:
• Aminoglycoside antibiotics : increased risk of nephrotoxicity and
ototoxicity
• Clozapine : increased risk of agranulocytosis, avoid concomitant
use
• Diuretics : increased risk of nephrotoxicity and ototoxicity
• Nephrotoxic drugs : increased nephrotoxicity ; not recommended
• Phenytoin : reduced absorption of the antiepileptic
• Warfarin : increased anticoagulant effect of warfarin
Comments
Offer scalp cooling (cold capping) to appropriate patients
Cumulative Doses
References
None
Controlled document
•
Slamon D, Eiermann,W, Robert N, Pienkowski T,Martin M,
Rolski J et al. on behalf of BCIRG006 Investigators. Phase III
Randomized Trial Comparing Doxorubicin and
Cyclophosphamide Followed by Docetaxel (AC T) with
Doxorubicin and Cyclophosphamide Followed by Docetaxel and
Trastuzumab (AC TH) with Docetaxel, Carboplatin and
Trastuzumab (TCH) in Her2neu Positive Early Breast Cancer
Patients: BCIRG 006 Study. San Antonio Breast Cancer
Symposium, 2009; Abstract 62
•
AL Jones, M Barlow, PJ Barrett-Lee, et al (2009) Management of
cardiac health in trastuzumab-treated patients with breast cancer:
updated United Kingdom National Cancer Research Institute
recommendations for monitoring. British Journal of Cancer 2009,
100. 684-692
•
Summary of Product Characteristics Taxotere® (Docetaxel) 20mg
and 80mg concentrate and solvent for infusion (Sanofi Aventis)
[internet] accessed 25/08/2010 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 25/08/2010
available from http://www.medicines.org.uk/EMC/medicine/23210
•
Summary of Product Characteristics Carboplatin 10mg/ml
Intravenous Infusion (Hospira) [internet] accessed 11/11/2010,
available at http://www.medicines.org.uk/EMC/medicine/622/SPC
•
Summary of Product Characteristics Herceptin® (Trastuzumab)
150mg powder for concentrate for solution for infusion (Roche)
[internet] accessed 28/10/2010, available from
Document No
Version Number
ASWCS10 BR021
1.1.a
Last printed 19/01/2011 *ONLY VALID ON DATE OF PRINTING*
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http://www.medicines.org.uk/EMC/medicine/3567/SPC
•
•
•
•
Daniels S. North London Cancer Network. Dose adjustment for
cytotoxics in renal impairment [internet]. accessed 21/05/2009
available at http://www.bopawebsite.org/tikidownload_file.php?fileId=620
Baxter K, editor. Stockley’s Drug Interactions. Pharmaceutical
Press; 2009. Accessed online on 21/05/09 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 21/05/09 available at
http://www.medicinescomplete.com/mc/hid/current/
Allwood M, Stanley A, Wright P, eds. The cytotoxic handbook, 4th
ed, Radcliffe Medical Press, 2002.
Document title
Document number
Approval date
Written by
TCH for Breast Cancer
ASWCS10 BR021
18/01/2011
Jeremy Braybrooke, Consultant Oncologist, BHOC
Checked by
Becky Bagnall, Consultant Pharmacist, NBT
Authorised by
Jeremy Braybrooke, Chair, ASWCS Drugs and
Therapeutics Committee
18/01/2012
Review date
Document reviewed by
Version number
Summary of changes
Controlled document
Jeremy Braybrooke
Becky Bagnall
Jeremy
Braybrooke
Digitally signed by Jeremy Braybrooke
DN: cn=Jeremy Braybrooke, o, ou,
[email protected], c=GB
Date: 2011.01.19 13:16:56 Z
Digitally signed by Becky Bagnall
DN: cn=Becky Bagnall, o, ou, [email protected].
uk, c=GB
Date: 2011.01.19 13:16:33 Z
Digitally signed by Jeremy Braybrooke
DN: cn=Jeremy Braybrooke, o, ou,
[email protected], c=GB
Date: 2011.01.19 13:17:17 Z
1.1.a
Version
Document No
Version Number
ASWCS10 BR021
1.1.a
Last printed 19/01/2011 *ONLY VALID ON DATE OF PRINTING*
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