Download Regimen: Carboplatin and Paclitaxel in combination with

Regimen: Carboplatin and Paclitaxel in combination with radiotherapy
for cancer of the oesophagus and oesophagogastric junction.
ICD10 codes pre-fixed with C15 and ICD10 code C16.0
Indication
Neoadjuvant treatment for resectable cancer of the oesophagus or
oesophagogastric junction.
Cases must be selected by the regional upper GI MDT
ECOG performance status 0-2.
Contraindications
Distant metastases
AST and/or ALT > 10 times the ULN
Total bilirubin > 1.5 x ULN
Weight loss > 10%
Tumour length >8cm
Regimen details
Day
Drug
Dose
Route
2
1,8,15,22,29
Paclitaxel
50mg/m
IV
1,8,15,22,29
Carboplatin
AUC* = 2
IV
*Dose (mg) = target AUC (mg/ml.min) x [GFR (ml/min) + 25]
Give pre-medication.
Paclitaxel should be administered before carboplatin.
Paclitaxel is administered in a 250ml sodium chloride 0.9% non-PVC
infusion bag with a 0.22 micron in-line filter over 1 hour.
Blood pressure & pulse should be monitored regularly (e.g. every 30
minutes) during paclitaxel infusion.
Carboplatin should be given in 250ml glucose 5% over 30 minutes.
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 infusions.
Facilities for the treatment of anaphylaxis, 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
and re-started at a slower infusion rate. Chlorphenamine 10mg iv may be
administered. Severe reactions, such as hypotension, dyspnoea,
bronchospasm, angioedema or generalised rash/erythema
require immediate discontinuation of infusion and appropriate therapy.
Avoid any device containing aluminium that may come into contact with
Carboplatin.
Paclitaxel and Carboplatin is given weekly for five weeks concurrent with
radiotherapy, starting the first day of radiotherapy.
Carboplatin is an irritant (Group 3)
Paclitaxel is a vesicant (Group5)
30 minutes prior to paclitaxel: Chlorphenamine 10mg IV, dexamethasone
8mg IV and ranitidine 50mg IV.
30minutes prior to carboplatin: oral 5HT3 antagonist (according to local
preference)
This regimen has moderate emetogenic potential – refer to local protocol
Administration
Frequency
Extravasation
Premedication
Emetogenicity
Additional
recommended
Controlled document
Document Number
ASWCS13 GI030
Version Number
0.1a
Last printed 15/01/2013 09:40:00 * Only valid on day of printing
Page 1 of 3
supportive
medication
Pre-treatment
evaluation
Regular
investigations
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
FBC
U+E
LFT
Baseline – results valid for 14 days
Baseline – results valid for 14 days
Baseline – results valid for 14 days
FBC
Pre day 8, 15, 22, 29. Results valid for 24 hours
U+E
Pre day 8, 15, 22, 29 Results valid for 24 hours
LFT
Pre day 8, 15, 22, 29 Results valid for 24 hours
Assess changes in neurological function weekly
Neutrophil count
≥1.0 x 109 /L
Platelet count
≥ 50 x 109 /L
Creatinine clearance
≤ULN; <20% change in GFR
Bilirubin
< 17 micromol/L
ALT/AST
<5 x ULN
If on day 8, 15, 22, 29, and 36 the WBC are < 1.0 × 109/L and/or platelets <
50 × 109/L, chemotherapy will be delayed by 1 week until recovery above
these values. In case of febrile neutropenia (granulocytes < 0.5 × 109/L and
fever > 38.5°C) or in case of severe bleeding or requiring ≥ 2 units of
platelet transfusions further chemotherapy will be withheld.
Platelets (x109/L)
Doses (both drugs)
ANC (x109/L)
≥ 1.0
and
≥ 50
100%
< 1.0
or
< 50
Delay for one week
Renal impairment
CrCl (ml/min
20
≤20
Carboplatin dose
Dose asnormal using
AUC
Contraindicated
Hepatic impairment
If bilirubin > 5 times the ULN, paclitaxel is contraindicated.
NCI Common
toxicity criteria
Toxicity
Definition
Arthralgia+/ or myalgia
Neuropathy
Rare or serious side effects
Adverse effects – the
contents of the table
indicate the adverse effects
that should be documented
on consent to treatment
forms
Controlled document
Febrile neutropenia
Myelosuppression
Urea and electrolyte disturbances
Neurotoxicity
Pulmonary fibrosis
Teratogenicity
Arrhythmias
Cardiac failure
Document Number
ASWCS13 GI030
Version Number
0.1a
Last printed 15/01/2013 09:40:00 * Only valid on day of printing
Dose adjustment
None
None
Frequently occurring side
effects
Nausea and vomiting
Alopecia
Diarrhoea or constipation
Fatigue/asthenia
Stomatitis and mucositis
Phlebitis
Allergic reactions
Myalgia+/or arthralgia
Page 2 of 3
Reduced fertility
Other
Significant drug
interactions – For full
details consult product
literature/reference texts
Oedema
Elderly patients may have a higher incidence of severe
neuropathy, severe myelosuppression, or
cardiovascular events compared to younger patients.
Paclitaxel is a CYP 2C8/9 and CYP 3A4 substrate. Drug levels may be
increased by inhibitors of these enzymes and decreased by inducers of
these enzymes.
Comments
Radiotherapy is given as follows: 41.4Gy in 23 fractions, 5 days per week.
Cumulative Doses
References
Gaast AV et al, the CROSS Study Group. Effect of preoperative concurrent chemoradiotherapy on
survival of patients with resectable esophageal or esophagogastric junction cancer: Results from a
multicenter randomized phase III study. Accessed online on 10/12/12. Available on:
http://www.asco.org/ascov2/Meetings/Abstracts?&vmview=abst_detail_view&confID=74&abstractID
=48745
Uptodate.com. Weekly carboplatin and paclitaxel chemotherapy with concurrent radiotherapy for
esophageal and esophagogastric junction (EGJ) cancer. Accessed online on 10/12/12. Available on
http://www.uptodate.com/contents/image?imageKey=ONC%2F68266&topicKey=ONC%2F85680&ra
nk=6%7E150&source=see_link&search=carboplatin+and+paclitaxel&utdPopup=true
BCCA Cancer Agency Protocol Summary for Neoadjuvant treatment of esophageal and
gastroesophageal carcinomas using carboplatin, paclitaxel and radiation therapy. Accessed online
on 10/12/12. Available on http://www.bccancer.bc.ca/NR/rdonlyres/C0A8933B-3AAD-4EBA-A95C4552A0A060C9/59944/UGIENACTRT_Protocol_12Oct2012.pdf
Summary of Product Characteristics. Paclitaxel 6mg/ml concentrate for solution for infusion.
Accessed online on 10/12/12. Available on
http://www.medicines.org.uk/EMC/medicine/21173/SPC/Paclitaxel+medac+6+mg+ml+concentrate+f
or+solution+for+infusion/
Summary of Product Characteristics. Carboplatin 10mg/ml concentrate for solution for infusion.
Accessed 10/12/12. Available online at
http://www.medicines.org.uk/EMC/medicine/25716/SPC/Carboplatin+10+mg+ml+concentrate+for+s
olution+for+infusion/
Document title
Document number
Approval date
Written by
Chemotherapy Protocol Template
ASWCS13 GI030
14/01/2013
Georgina Holmes. Pharmacist
UHBristol NHSFT.
Checked by
Steve Falk. Consultant Clinical
Steve Falk
Oncologist, UHBristol NHSFT
Jeremy Braybrooke, Chair ASWCS
Jeremy Braybrooke
Drugs and Therapeutics Committee
14/01/2015
Authorised by
Review date
Document reviewed by
Version number
Summary of changes
Controlled document
Version
Georgina Holmes
0.1.a
Document Number
ASWCS13 GI030
Version Number
0.1a
Last printed 15/01/2013 09:40:00 * Only valid on day of printing
Page 3 of 3
Digitally signed by Georgina Holmes
DN: cn=Georgina Holmes, o=NHS, ou=NHS,
[email protected], c=GB
Date: 2013.01.15 09:41:38 Z
Digitally signed by Steve Falk
DN: cn=Steve Falk, o, ou, [email protected], c=GB
Date: 2013.01.15 09:41:59 Z
Digitally signed by Jeremy Braybrooke
DN: cn=Jeremy Braybrooke, o, ou,
[email protected], c=GB
Date: 2013.01.15 09:42:17 Z