Regimen: Carboplatin single agent
Indications
1. Post surgical adjuvant or neoadjuvant (as in the EORTC 55791 trial) or
relapse therapy for stage IC to IV ovarian or primary peritoneal cancer or
fallopian tube cancer.
2. Relapse therapy initiated within 6 months of previous platinum based
therapy has a low response rate. Many patients may show higher
responses to non-platinum or dose-dense weekly regimens.
Regimen details
Administration
Day Drug
Dose
Route
1
Carboplatin
AUC 5 or 6* IV
*Dose (mg) = target AUC (mg/ml.min) x [GFR (ml/min) + 25]
Measured GFR (e.g. calculated using a patient specific method such as a
24-hour urine sample or 51Cr-EDTA/ DTPA measurement) is preferred
whenever feasible, particularly in circumstances of co-morbidity that could
affect renal function such as dehydrated patients or patients with a either a
high or low weight. Alternatively the Cockcroft & Gault Method can also be
used to estimate a patient’s GFR.
If using 24-hour urine or 51Cr-EDTA/DTPA is used, consider dosing at AUC5.
If using Cockcroft and Gault, consider dosing at AUC 6
Carboplatin should be given in 250 - 500ml glucose 5% over 30 - 60
minutes.
Avoid any device containing aluminium that may come into contact with
Carboplatin.
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
carboplatin. 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 restarted 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 carboplatin
and appropriate therapy.
Frequency
Every 21 days .
Extravasation
Usually 6 cycles.
(In a small number of neoadjuvant patients, it may be appropriate to debulk
after 6 cycles; in these cases, a further 2 cycles may be given post-surgery)
Carboplatin is an irritant (Group 3).
Premedication
Controlled document
None usually required although chlorphenamine 10mg IV + hydrocortisone
100mg IV should be given if there has been more than a 6 month gap
between courses of treatment due to a possible reaction to carboplatin
antibodies.
Document No
Version Number
ASWCS09 GYN001
1.1.a
Last printed 15/12/2011 15:58:00 *ONLY VALID ON DATE OF PRINTING*
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Emetogenicity
This regimen has moderate - high emetic potential – refer to local
protocol.
Additional
recommended
supportive medication
Loperamide 4mg po stat then 2mg prn if diarrhoea develops.
Mouthwashes as per local policy
Pre- treatment
evaluation
Regular investigation
Standard limits for
administration to go
ahead – if blood results not
within range, authorisation to
administer must be given by
prescriber/consultant
FBC
LFT
U&E (inc. SrCr,
Ca & Mg)
Ca125
EDTA/DTPA
assessment
Baseline - results valid for 28 days
Baseline - results valid for 28 days
Baseline - results valid for 28 days
FBC
LFT
U&E (inc. SrCr,
Ca & Mg)
Ca125
Clinical
Assessment
Pre D1 – results valid for 72 hours
Pre D1 – results valid for 7 days
Pre D1 – results valid for 7 days
Pre D1 – results valid for 28 days
Baseline if significant/suspected renal dysfunction
Pre D1 – results valid for 7 days
Clinically assess patient prior to each cycle,
particularly focusing on whether the patient has
developed renal dysfunction, neurotoxicity or
ototoxicity
Neutrophil count
Platelet count
Bilirubin
Creatinine Clearance
≥ 1 x 109/L
≥100 x 109/L
≤3 x ULN
> 30ml/min & <10% change in
GFR from previous cycle
Dose modifications
•
Haematological
toxicity
Day 1: If neutrophils <1.0 x 109/L and/or platelets <100 x 109/Ldelay 1
week or until recovery.
20% dose reduction should be considered if myelosuppression results in
delay of subsequent courses.
•
Renal
impairment
•
Hepatic
impairment
If the calculated GFR falls by more than10% from the previous cycle then
consider a dose alteration.
GFR ml/min
Carboplatin dose
≥30
Use AUC as per protocol
20-30 calculated EDTA then use AUC as per
protocol. Or consider
alternative non-nephrotoxic
regimen*
<20
Contra-indicated
*Clinician decision.
Transient increases in liver enzymes have been seen although no dose
reduction is usually required. If Bilirubin ≥3 x ULN and/or transaminases
>5 x ULN, discuss with consultant.
Controlled document
Document No
Version Number
ASWCS09 GYN001
1.1.a
Last printed 15/12/2011 15:58:00 *ONLY VALID ON DATE OF PRINTING*
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•
NCI Common
Toxicity Criteria
Toxicity
Febrile
neutropenia
Peripheral
neuropathy
Other toxicities
Adverse effects – the
contents of the table indicate
the adverse effects that should
be documented on consent to
treatment forms
Definition
ANC <0.5 x 109/L
plus fever requiring
IV antibiotics +/hospitalisation
≥ grade 3
Dose adjustment
Give a dose reduction of 1 x
AUC for all future doses of
carboplatin
≥ grade 3 toxicity
(except alopecia)
Defer therapy for 1 week until
resolved to ≤ grade 1 and then
continue with 20% dose
reduction.
Discuss with consultant if >1
week delay.
Discuss with consultant
•
Defer treatment for any grade 3/4 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
Rare or Serious Side Effects
Febrile neutropenia
Myelosuppression
Nephrotoxicity
U & E disturbances (especially
hypomagnesiumaemia,
hypokalaemia & hypocalcaemia)
Neurotoxicity (including
ototoxicity)
Risk of second malignancy e.g.
leukaemia
Hypersensitivity reactions
Pulmonary fibrosis (very rare)
Frequently occurring Side Effects
Nausea and vomiting
Mild alopecia
Diarrhoea or constipation
Fatigue / asthenia
Allergic reactions
Stomatitis and mucositis
Altered sense of taste
For full details of adverse effects and contraindications, see the Summary
of product characteristics (SPC).
Significant drug
interactions –
For full details consult product
literature/ reference texts
Comments
Controlled document
•
Warfarin/coumarin anticoagulants Avoid if possible as use often
causes an elevation or fluctuation in the INR – in the first instance
consider switching patient to a low molecular weight heparin during
treatment or if the patient continues taking an oral anticoagulant
monitor the INR at least once a week and adjust dose accordingly.
• 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
In patients with significant frailty or co-morbidity where chemotherapy is
nevertheless deemed appropriate, consider strategies to minimise toxicity
such as reducing the carboplatin dose to AUC 5 or AUC 4. Alternatively,
the treatment intensity may be attenuated by changing to q28d schedule.
Document No
Version Number
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Cumulative Doses
None.
References
•
•
•
•
Trimbos JB, Parmar M, Vergote I, Guthrie D, Bolis G, Colombo N, et al. International Collaborative
Ovarian Neoplasm trial 1 and Adjuvant ChemoTherapy In Ovarian Neoplasm trial: two parallel
randomized phase III trials of adjuvant chemotherapy in patients with early-stage ovarian
carcinoma. J Natl Cancer Inst 2003 95 (2): 105-12.
Colombo N, Guthrie D, Chiari S, Parmar M, Qian W, Swart AM, et al for the ICON1 Collaborators.
International Collaborative Ovarian Neoplasm Trial 1:A Randomized Trial of Adjuvant
Chemotherapy in
Women With Early-Stage Ovarian Cancer. J Natl Cancer Inst 2003 95 (2): 125-32.
Chan JK , Tian C, Fleming GF, Monk BJ, Herzog TJ, Kapp DS, et al. The potential benefit of 6 vs.
3 cycles of chemotherapy in subsets of women with early-stage high-risk epithelial ovarian cancer:
An exploratory analysis of a Gynecologic Oncology Group study. Gynecol Oncol 2010 116 (3): 301306.
•
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
•
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
•
•
•
•
Daniels S. North London Cancer Network. Dose adjustment for cytotoxics in hepatic
impairment [internet]. accessed 15/12/2010 available at http://www.bopawebsite.org/tikidownload_file.php?fileId=621
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, editors. The cytotoxics handbook. 4th ed. Radcliffe Medical Press.
2002.
Document title
Document number
Approval date
Written by
Checked by
Authorised by
Review date
Document
reviewed by
Version number
Summary of
changes
Controlled document
Carboplatin chemotherapy for breast cancer
ASWCS09 GYN001
11/12/2011
Dr Paul Cornes, Consultant Clinical
Oncologist, BHOC
Jarrod Dunn, Cancer Service Pharmacist,
TST
James Carr, Network Pharmacist, ASWCS
Jeremy Braybrooke, Chair, ASWCS Network
Chemotherapy Group
December 2013
Paul
Cornes
James Carr
Jeremy
Braybrooke
Digitally signed by Paul Cornes
DN: cn=Paul Cornes, o=BHOC,
ou=Consultant Oncologist, email=james.
[email protected], c=GB
Date: 2011.12.15 15:59:54 Z
Digitally signed by James Carr
DN: cn=James Carr, o=ASWCS, ou=Network
Pharmacist, [email protected], c=GB
Date: 2011.12.15 16:00:37 Z
Digitally signed by Jeremy Braybrooke
DN: cn=Jeremy Braybrooke, o, ou,
[email protected], c=GB
Date: 2011.12.15 16:01:14 Z
1.1.a
Version
Document No
Version Number
ASWCS09 GYN001
1.1.a
Last printed 15/12/2011 15:58:00 *ONLY VALID ON DATE OF PRINTING*
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