Download Regimen: Cisplatin and Gemcitabine

Regimen:
Indication
Cisplatin and Gemcitabine
Palliative Treatment for metastatic or locally advanced /unresectable Biliary
Tree cancers including Gall Bladder Cancer and Cholangiocarcinoma
ECOG Performance Status 0 – 2
Regimen detail
Administration
Day
1
1
8
8
Drug
Cisplatin
Gemcitabine
Cisplatin
Gemcitabine
Dose
25 mg/m2
1000 mg/m2
25 mg/m2
1000 mg/m2
Route
IV
IV
IV
IV
Cisplatin:
Pre hydration:1000 ml NaCl 0.9%+ 20 mmol KCl+ 8 mmol Mg S04 over 1 hr
Give Cisplatin dose in 500 ml NaCl 0.9% over 1 hr
Post Hydation – 500 ml NaCl 0.9% over 30 mins.
then
Gemcitabine: IV infusion in 250-500 ml NaCl 0.9% over 30 mins
Frequency
Total time:3 hours
Every 21 days for 6 to 8 cycles
Extravasation
Cisplatin is an exfoliant (Group 4)
Gemcitabine is a neutral agent (Group 1)
Premedication
None required
Emetogenicity
Moderate to high emetic potential – refer to local protocol
Additional recommended
supportive medication
Benzydamine (Difflam®) mouthwash
Loperamide 4mg stat then 2mg prn
Pre- treatment evaluation
Controlled document
FBC
LFT
U&E (inc. SrCr)
Baseline – results valid for 14 days
Baseline – results valid for 14 days
Baseline – results valid for 14 days
Document No
Version Number
ASWCS10 GI018
1.1.a
Last printed 03/12/2010 *ONLY VALID ON DATE OF PRINTING*
Page 1 of 5
Regular investigation
FBC
LFT
U&E (inc. SrCr)
Clinical
Assessment
Standard limits for
administration to go
ahead – if blood results not
Neutrophil count
Platelet count
Creatinine Clearance
Bilirubin
ALT +/- Alk Phos
within range, authorisation to
administer must be given by
prescriber/consultant
Pre D1 and D8 – results valid for 72 hours
Pre D1- results valid for 7 days
Pre D1- results valid for 7 days
Clinically assess patient prior to D1 of each cycle,
particularly focusing on whether the patient had
nausea, diarrhoea or stomatitis.
≥ 1 X 109/l
≥ 100 X 109/l
≥ 45 ml/hour
<1.5 x ULN
<5 x ULN
Dose modifications for
day 8 treatment
•
Haematological
toxicity (Gem)
ANC
(x 109/l)
≥1.0
0.5 – 1.0
< 0.5
Platelets (x
109/l)
and >100
or
50 – 100
or
<50
Gemcitabine
Cisplatin
dose
dose
100%
100%
75%
100%
Omit
Omit
*If a day 8 chemotherapy dose is missed or withheld due to toxicity, it will
not be given at a later date, i.e. the cycle will continue with the next day 1
treatment.
•
Renal impairment
For Cisplatin only
CrCl
> 45 ml/min
30-45 ml/min
<30ml/min
Cisplatin Dose
100%
Omit*
Omit*
Gemcitabine
100%
100%
Consider dose
reduction
*Consider carboplatin (AUC2) if CrCl <45 ml/min
•
Hepatic
impairment
Controlled document
No dose adjustments are necessary for hepatic impairment
Document No
Version Number
ASWCS10 GI018
1.1.a
Last printed 03/12/2010 *ONLY VALID ON DATE OF PRINTING*
Page 2 of 5
•
NCI Common
Toxicity Criteria
Toxicity
Febrile neutropenia
Neurotoxicity
Controlled document
Definition
ANC <0.5 x 109/l plus
fever requiring IV
antibiotics +/hospitalisation
Objective weakness
or sensory loss
interfering with
activities of daily life
Renal Toxicity
CrCl<45 ml/min
Stomatitis
Grade III painful
erythema or ulcers
requiring hydration
Document No
Version Number
ASWCS10 GI018
1.1.a
Last printed 03/12/2010 *ONLY VALID ON DATE OF PRINTING*
Dose Adjustment
Reduce dose of
Gemcitabine by 25%
Cisplatin should be
permanently stopped
and replaced with
carboplatin AUC5.
Continue with
gemcitabine
See above dose
reductions for
cisplatin
25% dose reduction
of gemcitabine days 1
and 8
Page 3 of 5
Adverse effects – the
contents of the table indicate
the adverse effects that
should be documented on
consent to treatment forms
Significant drug
interactions –
For full details consult
product literature/ reference
texts
Rare or Serious Side Effects
Febrile neutropenia
Myelosuppression
Interstitial Pneumonitis
Frequently occurring Side Effects
Nausea and vomiting
Fatigue
Rash
Oedema
Mucositis and Stomatitis
Constipation
Peripheral Neuropathy
Ototoxity
Nephrotoxicity
Influenza-like symptoms
Aminoglycoside antibiotics, when given concurrently or within 1-2 weeks
after cisplatin administration, may potentiate its nephrotoxic effects. Use of
other potentially nephrotoxic drugs (e.g. amphotericin B) is not
recommended during Cisplatin therapy.
Concurrent and/or sequential administration of ototoxic drugs such as
aminoglycoside antibiotics or loop diuretics may increase the potential of
Cisplatin to cause ototoxicity, especially in the presence of renal
impairment.
In patients receiving Cisplatin and phenytoin, phenytoin serum levels may
be decreased, possibly as a result of decreased absorption and/or
increased metabolism. In these patients, serum levels of phenytoin should
be monitored and dosage adjustments made as necessary.
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.
Comments
Cumulative Doses
References
Controlled document
none
1. Derby-Burton cancer network controlled document no. CCPG B87.
2. Kintzel PE, Dorr RT. Anticancer drug renal toxicity and elimination:
dosing guidelines for altered renal function Cancer Treat Rev 1995;
21: 33-64
3. Valle JW, Wasan HS, Palmer DD, Cunningham D, Anthoney DA,
Maraveyas A, et al. Gemcitabine with or without cisplatin in patients
(pts) with advanced or metastatic biliary tract cancer (ABC): Results
of a multicenter, randomized phase III trial (the UK ABC-02 trial). J
Clin Oncol 27:15s, 2009 (suppl; abstr 4503)
4. Heinemann V; Quietzsch D; Gieseler F, Gonnermann M, Schönekäs
H, Rost A, et al Randomized phase III trial of gemcitabine plus
cisplatin compared with gemcitabine alone in advanced pancreatic
cancer. J Clin Oncol 2006;24(24):3946-52.
5. British Columbia Cancer Agency Protocol Summary for First-line
Palliative Chemotherapy for Advanced Gallbladder Cancer and
Cholangiocarcinoma using Gemcitabine and Cisplatin [internet],
viewed 07/10/2010, available at
http://www.bccancer.bc.ca/NR/rdonlyres/C0A8933B-3AAD-4EBAA95C-4552A0A060C9/46104/GIAVPG_Protocol_Jul2010.pdf
6. Daniels S. North London Cancer Network. Dose adjustment for
cytotoxics in hepatic impairment [internet]. accessed 07/10/2010
available at http://www.bopawebsite.org/tikidownload_file.php?fileId=621
7. Daniels S. North London Cancer Network. Dose adjustment for
cytotoxics in renal impairment [internet]. accessed 07/10/2010
Document No
Version Number
ASWCS10 GI018
1.1.a
Last printed 03/12/2010 *ONLY VALID ON DATE OF PRINTING*
Page 4 of 5
available at http://www.bopawebsite.org/tikidownload_file.php?fileId=620
8. Summary of Product Characteristics Gemzar® (Gemcitabine)
200mg powder for solution for infusion, 1g powder for solution for
infusion (Eli Lilly) [internet], accessed 07/10/2010 available from
http://www.medicines.org.uk/EMC/medicine/596/SPC
9. Summary of Product Characteristics Cisplatin 1 mg/ml Sterile
Concentrate (Hospira) [internet] accessed 07/10/2010 available from
http://www.medicines.org.uk/EMC/medicine/623/SPC
10. Baxter K, editor. Stockley’s Drug Interactions. Pharmaceutical Press;
2009. Accessed on line on 07/10/2010 available at
https://www.medicinescomplete.com/mc/
11. Trissel LA. Handbook of Injectable Drugs, 15th edition. American
Society for Health-Systems Pharmacists 2009. Accessed on line on
07/10/2010 available at
http://www.medicinescomplete.com/mc/hid/current/
12. Allwood M, Stanley A, Wright P, editors. The cytotoxics handbook.
4th ed. Radcliffe Medical Press. 2002.
Document title
Document number
Approval date
Written by
GemCis for metastatic or locally advanced /unresectable biliary tree cancers including Gall
Bladder Cancer and Cholangiocarcinoma
ASWCS10 GI018
04/11/2010
Stephen Falk, Consultant Clinical Oncologist BHOC
Checked by
James Carr, Network Pharmacist, ASWCS
James Carr
Authorised by
Jeremy Braybrooke, Chair ASWCS Drugs and
Therapeutics Committee
04/11/2011
Jeremy
Braybrooke
Review date
Document reviewed by
Version number
Summary of changes
Controlled document
Steve Falk
Digitally signed by Steve Falk
DN: cn=Steve Falk, o, ou, [email protected], c=GB
Date: 2010.12.03 17:51:30 Z
Digitally signed by James Carr
DN: cn=James Carr, o=ASWCS, ou=ASWCS,
[email protected], c=GB
Date: 2010.12.03 17:51:57 Z
Digitally signed by Jeremy Braybrooke
DN: cn=Jeremy Braybrooke, o, ou,
[email protected], c=GB
Date: 2010.12.03 17:52:27 Z
1.1.a
Document No
Version Number
ASWCS10 GI018
1.1.a
Last printed 03/12/2010 *ONLY VALID ON DATE OF PRINTING*
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