Download Regimen: Liposome-encapsulated Doxorubicin (Myocet )

Regimen: Liposome-encapsulated Doxorubicin (Myocet®)
1. NICE approved indication (TA91) - Pegylated Liposome-encapsulated
Doxorubicin Hydrochloride is recommended as an option for the second-line
(or subsequent) treatment of women with partially platinum-sensitive, platinum
resistant or platinum-refractory advanced ovarian cancer, and for women who
are allergic to platinum-based compounds. In November 2011, Janssen
Pharmaceuticals announced that there is a worldwide lack of Caelyx and
stocks were expected to run out in December 2011. The company is unable to
provide a date when Caelyx may return to the market. In the absence of
Caelyx, Myocet® provides an alternative treatment option in this setting.
2. Palliative therapy for relapsed ovarian, fallopian tube or primary peritoneal
cancer. This is an off licence indication which has been endorsed by the
NCRI Ovarian Subgroup.
Indications
Regimen detail
Administration
This is NOT a NICE-approved treatment for fallopian tube or primary
peritoneal cancer. Please ensure that this regimen is locally funded
before prescribing this treatment or discussing with patients.
Day
Drug
Dose
Route
1
Liposome-encapsulated Doxorubicin 40-60mg/m2 *
IV
Hydrochloride (Myocet®)
*Although 60mg/m2 is the dose used in several trials in ovarian cancer, many
patients may not tolerate this dose and clinicians may choose to commence at
the lower dose of 50mg/m2 and dose escalate as tolerated. Heavily pre-treated
patients may be commenced at 40mg/m2.
Liposome-encapsulated Doxorubicin Hydrochloride is administered in glucose
5% or 0.9% NaCl infusion bag at a final concentration of 0.4mg/ml to 1.2mg/ml
over one hour.
Infusions must not be filtered.
Liposome-encapsulated Doxorubicin Hydrochloride can be associated with an
infusion reaction, which usually occurs during the first cycle. If a reaction
occurs, the infusion should be stopped until symptoms have resolved and can
be recommenced at a slower rate. Hydrocortisone 100mg IV bolus and
chlorphenamine 10mg IV bolus may be administered if appropriate.
Frequency
Every 28 days for a maximum of 6 cycles
Extravasation
Liposome-encapsulated Doxorubicin Hydrochloride is an exfoliant (Group 4)
Pre-medication
Infusion associated reactions have been reported, including flushing,
dyspnoea, fever, facial swelling, back pain, chest pain and hypotension.
Dexamethasone 16-20mg IV 30 minutes before Myocet are recommended.
Chlorphenamine 10mg IV and Ranitidine 50mg IV 30 minutes before
chemotherapy may also be considered.
Emetogenicity
This regimen has moderate-low emetic potential – refer to local protocol.
Controlled document
Document No
ASWCS12 GYN016
*ONLY VALID ON DATE OF PRINTING*
Version Number
1.1.a
Page 1 of 4
Additional
recommended
supportive medication
Loperamide 4mg po stat then 2mg prn if diarrhoea develops.
Mouthwashes as per local policy.
Pre- treatment
evaluation
FBC
Baseline - results valid for 28 days
LFT
Baseline - results valid for 28 days
U&E (inc. SrCr) Baseline - results valid for 28 days
Ca125
Pre D1 (if applicable) – results valid for 28 days
ECHO
Only required if clinically indicated*
* Significantly less cardiac toxicity has been reported in patients treated
with Myocet® compared to conventional doxorubicin at the same dose in
mg, however, baseline cardiac assessment may be desirable and
potassium levels must be monitored regularly.
Regular investigations
FBC
LFT
U&E (inc. SrCr)
Ca125
Clinical
Assessment
Standard limits for
administration to go
ahead – if blood results not
Neutrophil count
Platelet count
Creatinine Clearance
Bilirubin
ALT/AST
within range, authorisation to
administer must be given by
prescriber/consultant
Pre D1 – results valid for 72 hours
Pre D1 – results valid for 7 days
Pre D1 – results valid for 7 days
Pre D1 (if applicable ) – results valid for 7 days
Clinically assess patient prior to each cycle
≥ 1.0 x 109/L
≥100 x 109/L
> 30ml/min
< 20micromol/L
< 60iu/L
Dose modifications
Haematological toxicity
Defer therapy for 1 week if:
• Neutrophils <1.0 x 109/L or Platelets < 100 x 109/L
Renal impairment
No dosage adjustment required.
Hepatic impairment
Serum bilirubin (micromol/L)
<20
20-51
51-68
>68
Liposome-encapsulated
Doxorubicin Hydrochloride Dose
100%
75%*
50%*
Avoid
* If the first dose is tolerated without an increase in bilirubin or serum
trasnaminases, the second dose can be increased to the next dose increment
and then titrated to full dose on subsequent cycles if again tolerated.
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ASWCS12 GYN016
*ONLY VALID ON DATE OF PRINTING*
Version Number
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NCI Common
Toxicity Criteria
Toxicity
Febrile
neutropenia
Stomatitis
Definition
ANC <0.5 x 109/l
plus fever requiring
IV antibiotics +/hospitalisation
Grade 2 (painful
erythema, oedema
or ulcers, but can
eat)
Grade 3 (painful
erythema, oedema
or ulcers, and
cannot eat)
Other toxicities
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
Dose adjustment
Reduce dose by 25% for all future
doses of Liposome-encapsulated
Doxorubicin Hydrochloride.
Treat symptomatically and/or delay
until recovered to
Grade 1. If symptoms continue,
reduce dose of Liposomeencapsulated Doxorubicin
Hydrochloride by 25%.
Treat symptomatically and delay
until recovered to Grade 1 and then
reduce dose of Liposomeencapsulated Doxorubicin
Hydrochloride by 25%
Discontinue treatment
Grade 4 (requires
parenteral or enteral
support)
Grade 3 toxicity
Reduce dose of Liposome(except alopecia,
encapsulated Doxorubicin
nausea & vomiting) Hydrochloride by 10mg/m2
provided toxicity has resolved to ≤
Grade 1.
If further toxicity occurs, an
additional reduction may be made
after discussion with consultant
Grade 4 toxicity
Withhold treatment and discuss
(except alopecia,
with consultant
nausea & vomiting)
If a delay of more than 4 weeks is required for recovery, or more than two
dose reductions are necessary, the patient should discontinue treatment.
Rare but Serious Side Effects
Frequently occurring Side Effects
Cardiac toxicity
Nausea and vomiting
Venous thromboembolism
Alopecia (reversible)
Secondary leukaemias
Diarrhoea or constipation
Hyperglycaemia
Fatigue / asthenia
Acute Hypersensitivity reactions
Discoloured urine
Stomatitis and mucositis
(first infusion)
Anorexia
Myelosuppression
Can cause dizziness – do not drive or
operate machinery
Warfarin/coumarin anticoagulants Use may cause an elevation or fluctuation
in the INR. In the first instance consider switching patient to a low molecular
weight heparin during treatment. If the patient continues taking an oral
anticoagulant monitor the INR at least once a week and adjust dose
accordingly.
Ciclosporin, Verapamil, paclitaxel and other P-glycoproteins (P-Gp)
inhibitors will increase plasma levels of doxorubicin and its metabolite
doxorubicinol. Care needs to be taken when giving doxorubicin with high doses
of ciclosporin as this can lead to neurotoxicity.
Controlled document
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ASWCS12 GYN016
*ONLY VALID ON DATE OF PRINTING*
Version Number
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Concomitant therapy with other liposomal or lipid-complexed substances
including fat emulsions could change the pharmacokinetic profile of Myocet
Interactions with doxorubicin (not specifically Myocet) have been reported with
streptozocin, phenobarbital and phenytoin.
Concomitant treatment with other substances reported to be cardiotoxic or
cardiologically active (eg calcium antagonists) increase the risk of cardiotoxicity
Comments
Cumulative Doses
Myocet must not be used in pregnancy unless absolutely necessary.
Women of child bearing potential should avoid pregnancy during treatment and
for 6 months after discontinuation of therapy.
Women receiving Myocet should not breastfeed.
Use with caution at cumulative doses in excess of 450mg/m2 (or equivalent
antracycline dosage). Consider previous anthracycline exposure.
References
•
Rose PG. Pegylated liposome-encapsulated doxorubicin: optimizing the dosing schedule in ovarain
cancer. The Oncologist. 2004;10 (3):205–14.
•
Daniels S. North London Cancer Network. Dose adjustment for cytotoxics in hepatic impairment
[internet]. Accessed 09/12/2010 at http://www.bopawebsite.org/tiki-download_file.php?fileId=621
•
Daniels S. North London Cancer Network. Dose adjustment for cytotoxics in renal impairment [internet].
Accessed 09/12/2010 at http://www.bopawebsite.org/tiki-download_file.php?fileId=620
•
Summary of Product Characteristics Myocet® (Liposome–encapsulated doxorubicin–citrate complex)
powder and pre-admixtures for concentrate for liposomal dispersion for infusion (Cephalon) [internet],
accessed 20/07/2012 available from http://www.medicines.org.uk/EMC/medicine/5945/SPC
•
Baxter K, editor. Stockley’s Drug Interactions. Pharmaceutical Press; 2009. Accessed on line
(09/12/2010) https://www.medicinescomplete.com/mc/
•
Angioli R, Palaia I, Calcagno M, Manci N, Zullo MA, Bellati F, et al. Liposome-encapsulated doxorubicin
citrate in previously treated recurrent/metastatic gynecological malignancies. Int J Gynecol Cancer 2007
17(1):88-93.
Angelucci M, Zullo MA, Terranova C, Montera R, Guzzo F, De Oronzo MA, et al. Use of Myocet as a valid
drug in patients affected by ovarian cancer suffering from chemotherapy side-effects. ESGO 2011
abstract 297
Eichbaum M, Thum J, Mayer C, Gebauer G, Mallmann P, Marme F, et al. Non-pegylated liposomeencapsulated doxorubicin as second-line therapy for patients with platinum-refractory recurrent ovarian
cancer: Preliminary data of a multicenter phase II trial; Archives of Gynecology and Obstetrics, October
2010, vol./is. 282/(S128)
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Document title
Document number
Approval date
Written by
Liposome-encapsulated Doxorubicin Hydrochloride (Myocet ) chemotherapy for ovarian cancer
ASWCS12 GYN016
24/07/2012
Rebecca Bowen, Consultant Oncologist, RUH Bath Cancer Centre
Checked by
James Carr, Network Pharmacist, ASWCS
James Carr
Authorised by
Review date
Document reviewed by
Version number
Summary of changes
Jeremy Braybrooke, Chair, ASWCS Network Chemotherapy Group
24/07/2013
Jeremy Braybrooke
Rebecca Bowen
Digitally signed by Rebecca Bowen
DN: cn=Rebecca Bowen, o=RUH Bath, ou=RUH Bath, email=james.
[email protected], c=GB
Date: 2012.07.27 11:45:03 +01'00'
Digitally signed by James Carr
DN: cn=James Carr, o=ASWCS, ou=Network Pharmacist,
[email protected], c=GB
Date: 2012.07.27 11:45:36 +01'00'
Digitally signed by Jeremy Braybrooke
DN: cn=Jeremy Braybrooke, o, ou, [email protected], c=GB
Date: 2012.07.27 11:46:09 +01'00'
1.1.a
Version
Controlled document
Document No
ASWCS12 GYN016
*ONLY VALID ON DATE OF PRINTING*
Version Number
1.1.a
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