Download Regimen : Cisplatin and Capecitabine

Regimen : Cisplatin and Capecitabine
Indications
Regimen details
Administration
• Palliative therapy for stage IV or relapsed squamous cell
oesophageal cancer
• 2 courses as induction therapy prior to surgery or definitive irradiation
• Concomitant chemo-radiation for oesophageal cancer
Day
Drug
Dose
Route
2
1
Cisplatin
60mg/m
IV infusion
2
PO
1-21
Capecitabine
625mg/m twice daily
Pre hydration:1000 ml Sodium Chloride 0.9% over 60 minutes
200ml Mannitol 20% over 30 min OR 400ml Mannitol 10% over 30 min
Cisplatin is administered in 500 ml Sodium Chloride 0.9% over 60
minutes
Post Hydration: 1000 ml Sodium Chloride 0.9% + 20 mmol Potassium
Chloride+ 8 mmol Magnesium Sulphate over 2 hours.
An accurate fluid balance record should be kept.
Advise patients to drink at least 2 litres or fluid over the next 24 hours.
Cisplatin may interact with metal aluminium to form a black precipitate
of platinum. All aluminium-containing IV sets, needles, catheters and
syringes should be avoided.
Capecitabine is available as 150mg and 500mg tablets
(refer to dose calculations table). Tablets should be taken within 30
minutes after morning and evening meals.
Dose level 625mg/m2 bd
Body Surface Area (m2)
Dose (mg) to be given twice daily
1.25 – 1.36
800
Frequency
Extravasation
Premedication
Emetogenicity
Additional
recommended
supportive
medication
Controlled document
1.37 – 1.52
1000 morning, 800 evening
1.53 – 1.66
1000
1.67– 1.78
1150 morning, 1000 evening
1.79– 1.90
1150
1.91 – 2.04
1500 morning, 1000 evening
2.05 – 2.16
1300
2.17 – 2.32
1500 morning, 1300 evening
≥2.33
1500
Every 21 days for up to 4 cycles
Cisplatin is an exfoliant (Group 4)
Capecitabine is an oral agent.
Pre-hydration as above.
This regimen has high emetogenic potential – refer to local protocol
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Mouthwashes as per local policy.
Loperamide 4mg po stat then 2mg prn if diarrhoea develops.
Pyridoxine 50 mg tds reduces the severity of plantar-palmar
erythrodyaesthesia (PPE). It should be given for any grade PPE
and should be continued until the end of treatment.
Document Number
ASWCS11 GI006
Version Number
1.2.a
Last printed 20/07/2012 10:54:00 * Only valid on day of printing
Page 1 of 5
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
Renal impairment
Hepatic
impairment
FBC
U+E (incl SrCr)
LFT
Mg2+ and Ca2+
FBC
U+E (incl SrCr)
LFT
Mg2+ and Ca2+
Neutrophil count
Platelet count
Creatinine clearance
AST/ALP
Bilirubin
Defer therapy for 1 week if neutrophils <1.0 x 109/L or platelets < 100 x 109/L
and then resume capecitabine and cisplatin at 75% dose
CrCl (ml/min)
Cisplatin Dose
Capecitabine
Dose
>60
100%
100%
50-60
75%
100%
45-49
50% OR Substitute with
75%
Carboplatin AUC 5
30-44
Substitute with Carboplatin
75%
AUC 5
20-29
Substitute with Carboplatin
Omit
AUC 5
<20
Carboplatin contraindicated
Omit
AST +/- ALT
≤ 2.5 x ULN
2.5-5 x ULN
>5 x ULN
NCI Common
toxicity criteria
Toxicity
Febrile
neutropenia
Diarrhoea
(Capecitabine)
Controlled document
Baseline – results valid for 7 days
Baseline – results valid for 7 days
Baseline – results valid for 7 days
Baseline – results valid for 7 days
Results valid for 72 hrs
Results valid for 7 days
Results valid for 7 days
Results valid for 7 days
≥1.0 x 109/L
≥100 x 109/L
≥60ml/min
≤1.5 x ULN
≤26micromol/L
Document Number
ASWCS11 GI006
Bilirubin
Cisplatin
dose
100%
100%
Capecitabine
dose
≤ 3.0 x ULN
100%
> 3.0 x ULN
Discuss with
consultant.
Current
evidence
suggests safe
> 5 x ULN
Omit Treatment unless secondary
to biliary obstruction
Definition
Dose adjustment
9
ANC <0.5 x 10 /L plus
Delay until FBC recovers
fever requiring IV
then reduce both cisplatin
antibiotics +/and capecitabine to 50%
hospitalisation
dose
Grade 2: Increase of 4 - 6
stools per day over
baseline; moderate
increase in ostomy output
Version Number
1.2.a
Last printed 20/07/2012 10:54:00 * Only valid on day of printing
Delay until ≤ Grade 1 then
resume at 100%
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Palmar-Plantar
Erythrodyaesthesia
(Hand-Foot
Syndrome)
(Capecitabine)
compared to baseline
Grade 3/4: Increase of
>=7 stools per day
over baseline;
incontinence;
hospitalization indicated;
severe increase in ostomy
output compared to
baseline
Grade 1: Minimal skin
changes or dermatitis
(e.g., erythema,
edema, or hyperkeratosis)
Discomfort but no pain; no
interruption of ADL
Grade 2: Skin changes
(e.g., peeling, blisters,
bleeding, edema, or
hyperkeratosis)
Pain; limiting instrumental
ADL
Grade 3: Severe skin
changes (e.g.,peeling,
blisters, bleeding,
edema, or hyperkeratosis)
Pain; limiting self care
ADL
Controlled document
Neurotoxicity/
Ototoxocity
(Cisplatin)
≥Grade 2 Neuropathy or
Ototoxicity
Stomatitis
Grade 1: painless ulcers,
erythema, mild soreness
Grade 2: painful
erythema,
edema, or ulcers but can
eat or swallow
Grade 3: painful
erythema, edema, or
ulcers requiring IV
hydration, and cannot eat
Grade 4: severe
ulceration or requires
parenteral or enteral
nutritional support or
prophylactic intubation.
Document Number
ASWCS11 GI006
Version Number
1.2.a
Last printed 20/07/2012 10:54:00 * Only valid on day of printing
Delay until ≤ Grade 1 then
resume at 75%
Treat symptomatically and
maintain doses at 100%
1st appearance: delay until
≤ Grade 1 then resume
capecitabine at 75%
(cisplatin at 100%)
2nd appearance: delay until
≤ Grade 1 then resume
capecitabine at 50%
(cisplatin at 100%)
3rd appearance:
discontinue permanently
1st appearance: delay until
≤ Grade 1 then resume
capecitabine at 50%
(cisplatin at 100%)
2nd appearance:
discontinue or delay until ≤
Grade 1 then resume
capecitabine at 50%
(cisplatin at 100%)
Cisplatin should be
permanently stopped and
replaced with carboplatin
AUC5.
100%
Omit until toxicity ≤ Grade
1, then resume cisplatin
and capecitabine at 75%
Omit until toxicity ≤ Grade
1, then resume cisplatin
and capecitabine at 50%
Discontinue OR Omit until
toxicity ≤ Grade 1, then
resume cisplatin and
capecitabine at 50%
Page 3 of 5
Adverse effects –
Rare but serious side effects
Frequently occurring side effects
the contents of the
table indicate the
adverse effects that
should be documented
on consent to treatment
forms
Febrile neutropenia
Palmar-plantar erythrodyaesthesia
(PPE) / Hand-foot syndrome (HFS)
Stomatitis and mucositis
Nausea/vomiting
Fatigue / asthenia
Myelosuppression
Thrombosis/embolism
Cardiac toxicity including
arrhythmias or ischaemia
Ocular Toxicity
Other
Significant drug
interactions – For
full details consult
product
literature/reference
texts
Diarrhoea
Ototoxicity
Neurotoxicity
Skin reactions, nail changes, taste disturbances
Coumarin-derived anticoagulants such as warfarin – patients
established on warfarin should either be changed to low molecular weight
heparin or have weekly monitoring of INR. Patients who are initiated on
anti-coagulation should remain on low molecular weight heparin until
completion of the course of capecitabine-cisplatin.
Allopurinol and antigout agents: interactions have been observed
between allopurinol and fluorouracil with possible decreased efficacy of
fluorouracil. Concomitant use of allopurinol with capecitabine should be
avoided. Cisplatin may increase the concentration of blood uric acid. Thus,
in patients concurrently receiving antigout agents such as allopurinol,
colchicine, probenecid or sulfinpyrazone, dosage adjustment of these
drugs may be necessary to control hyperuricemia and gout.
Phenytoin and fosphenytoin: close monitoring and/or alternative agents
are recommended if co-prescribed with any of these agents. Phenytoin
serum levels may be decreased, possibly as a result of decreased
absorption and/or increased metabolism.
Capecitabine:
Sorivudine and its analogues – co-administration causes increased
fluoropyrimidine toxicity which may be fatal
Folinates Avoid concomitant use of folinic and folic acid – enhanced toxicity of
capecitabine
Antacids – the use of antacids with capecitabine can decrease absorption –
avoid.
Comments
Cumulative
Doses
References
Controlled document
Cisplatin:
Concurrent and/or sequential administration of ototoxic or nephrotoxic
drugs such as aminoglycoside antibiotics, loop diuretics and amphotericin
B may increase the occurrence of these toxicities, especially in the
presence of renal impairment.
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 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.
N/A
•
Lee SS, Kim S-B, Park S-I, Kim YH, Ryu J-S. Song H-Y, et al.
Capecitabine and Cisplatin Chemotherapy (XP) Alone or
Document Number
ASWCS11 GI006
Version Number
1.2.a
Last printed 20/07/2012 10:54:00 * Only valid on day of printing
Page 4 of 5
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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
Sequentially Combined Chemoradiotherapy Containing XP
Regimen in Patients with Three Different Settings of Stage IV
Esophageal Cancer. Jpn J Clin Oncol 2007; 37 (11): 829-835.
Lee J, Im YH, Cho EY, Hong YS, Lee HR, Kim HS, et al. A phase II
study of capecitabine and cisplatin (XP) as first-line chemotherapy
in patients with advanced esophageal squamous cell carcinoma.
Cancer Chemother Pharmacol 2008; 62 (1): 77-84. please confirm
if these two references are (a) appropriate and (b) sufficient
NCI Common Terminology Criteria for Adverse Events (CTCAE)
version 4.03 [internet] accessed 04/02/2011 available at
http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-0614_QuickReference_5x7.pdf
Daniels S. North London Cancer Network. Dose adjustment for
cytotoxics in hepatic impairment [internet]. accessed 04/02/2011
available at http://www.bopawebsite.org/tikidownload_file.php?fileId=621
Daniels S. North London Cancer Network. Dose adjustment for
cytotoxics in renal impairment [internet]. accessed 04/02/2011
available at http://www.bopawebsite.org/tikidownload_file.php?fileId=620
Summary of Product Characteristics Xeloda® (Capecitabine)
500mg and 150mg Tablets (Roche) [internet], accessed 04/02/2011
available from
http://www.medicines.org.uk/EMC/medicine/4619/SPC/Xeloda/
Summary of Product Characteristics Cisplatin 1mg/ml sterile
concentrate (Hospira) [internet].accessed 04/02/2011 available
from http://www.medicines.org.uk/EMC/medicine/623/SPC
Baxter K, editor. Stockley’s Drug Interactions. Pharmaceutical
Press; 2009. Accessed on line on 04/02/2011 available at
https://www.medicinescomplete.com/mc/
Allwood M, Stanley A, Wright P, editors. The cytotoxics handbook.
4th ed. Radcliffe Medical Press. 2002.
Cisplatin and Capecitabine
ASWCS11 GI006
19/07/2011
Stephen Falk, Consultant Clinical
Oncologist BHOC
James Carr, Network Pharmacist,
ASWCS
Jeremy Braybrooke, Chair ASWCS
Drugs and Therapeutics Committee
19/07/2013
Version
Steve Falk
James Carr
Jeremy
Braybrooke
Digitally signed by Steve Falk
DN: cn=Steve Falk, o, ou, email=james.
[email protected], c=GB
Date: 2012.07.20 10:55:42 +01'00'
Digitally signed by James Carr
DN: cn=James Carr, o=ASWCS, ou=Network
Pharmacist, [email protected], c=GB
Date: 2012.07.20 10:56:10 +01'00'
Digitally signed by Jeremy Braybrooke
DN: cn=Jeremy Braybrooke, o, ou,
[email protected], c=GB
Date: 2012.07.20 10:56:41 +01'00'
1.2.a: amended July 2012 to include the option of Mannitol 10%
Document Number
ASWCS11 GI006
Version Number
1.2.a
Last printed 20/07/2012 10:54:00 * Only valid on day of printing
Page 5 of 5