Download Pegylated Liposomal Doxorubicin Hydrochloride (Caelyx ® )

Regimen: Pegylated Liposomal Doxorubicin Hydrochloride PLDH (Caelyx®)
Indications
1. NICE approved indication (TA91) - Pegylated Liposomal 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.
2. Palliative therapy for relapsed ovarian, fallopian tube or primary
peritoneal cancer
Regimen details
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(s) Drug
Dose
Route
1
Pegylated Liposomal Doxorubicin 40IV
Hydrochloride
50mg/m2 *
*Although 50mg/m2 is the licensed dose, most patients do not tolerate this
dose and clinicians may choose to commence at a lower dose.
Pegylated Liposomal Doxorubicin Hydrochloride is administered in 250ml
glucose 5% infusion bag.
For doses over 90mg administer in a 500ml glucose 5% infusion bag.
Pegylated Liposomal Doxorubicin Hydrochloride should be given at
1mg/minute for the first cycle. If well tolerated then subsequent doses can
be administered over 60 minutes.
Infusions must not be filtered.
Pegylated Liposomal 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
Pegylated Liposomal Doxorubicin Hydrochloride is an exfoliant (Group 4)
Pre-medication
None usually required
Emetogenicity
This regimen has moderate-low 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.
To minimise the risk of PPE for the first week after Pegylated Liposomal
Doxorubicin Hydrochloride infusion:
Controlled document
•
Keep hands and feet as cool as possible.
•
Avoid tight-fitting gloves, sock, footwear and high-heeled shoes.
Document No
Version Number
ASWCS09 GYN007
1.1.a
Last printed 15/12/2011 16:39:00 *ONLY VALID ON DATE OF PRINTING*
Page 1 of 4
•
Avoid exposing the skin to very hot water.
•
Avoid vigorous rubbing of skin-pat skin dry after washing.
•
Pre- treatment
evaluation
Avoid use of topical anaesthetics as these can worsen skin
reactions.
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 – results valid for 28 days
ECHO
Only required if clinically indicated
Regular investigation
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 – results valid for 7 days
Clinically assess patient prior to each cycle,
particularly focusing on whether the patient has
developed marked stomatitis, Palmar-Plantar
Erythrodysaesthesia or neurotoxicity
≥ 1.0 x 109/L
≥100 x 109/L
> 30ml/min
< 20μmol/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
NCI Common Toxicity
Criteria
Controlled document
Serum bilirubin (micromol/L)
Pegylated Liposomal Doxorubicin
Hydrochloride Dose
<20
100%
20-51
75%*
51-68
50%*
>68
Avoid
* If the first dose is tolerated without an increase in bilirubin or LFTs, the
second dose can be increased to the next dose increment and then titrated
to full dose on subsequent cycles if again tolerated.
Toxicity
Febrile
neutropenia
Definition
ANC <0.5 x 109/l plus
fever requiring IV
antibiotics +/hospitalisation
Dose adjustment
Reduce dose by 25% for all
future doses of Pegylated
Liposomal Doxorubicin
Hydrochloride.
Stomatitis
Grade 2 (painful
erythema, oedema or
ulcers, but can eat)
Treat symptomatically and/or
delay until recovered to
Grade 1. If symptoms continue,
Document No
Version Number
ASWCS09 GYN007
1.1.a
Last printed 15/12/2011 16:39:00 *ONLY VALID ON DATE OF PRINTING*
Page 2 of 4
PPE (HandFoot
Syndrome)
Other
toxicities
reduce dose of Pegylated
Liposomal Doxorubicin
Hydrochloride by 25%.
Grade 3 (painful
Treat symptomatically and delay
erythema, edema or
until recovered to Grade 1 and
ulcers, and cannot eat) then reduce dose of Pegylated
Liposomal Doxorubicin
Hydrochloride by 25%.
.
Grade 4 (requires
Discontinue treatment
parenteral or enteral
support)
Grade 2
Treat symptoms until recovered
to ≤Grade 1. If patient not
recovered to ≤Grade 1 by 42
days after previous dose,
discontinue treatment
Grade 3 or 4
Discontinue treatment
Grade 3 toxicity
(except alopecia,
nausea & vomiting)
Grade 4 toxicity
(except alopecia,
nausea & vomi ing)
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
Reduce dose of Pegylated
Liposomal Doxorubicin
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
Withhold treatment and discuss
with consultant
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
Frequently occurring Side Effects
Febrile neutropenia
Nausea and vomiting
Myelosuppression
Alopecia (reversible)
Peripheral neuropathy
Possible diarrhoea or constipation
Convulsions
Fatigue / asthenia
Thromboembolism
Stomatitis and mucositis
Allergic reactions such as rash and
Secondary leukaemias
pruritus
Optic neuritis
Acute Hypersensitivity reactions
Palmar-Plantar Erythrodysaesthesia
(first infusion)
(PPE) / Hand-Foor Syndrome (HFS)
Cardiac toxicity
Discoloured urine
Warfarin/coumarin anticoagulants Avoid if possible-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.
Ciclosporin Care needs to be taken when giving doxorubicin with high
doses of ciclosporin as this can lead to neurotoxicity.
Controlled document
Document No
Version Number
ASWCS09 GYN007
1.1.a
Last printed 15/12/2011 16:39:00 *ONLY VALID ON DATE OF PRINTING*
Page 3 of 4
Comments
The licensed dose by the EMEA is 50mg/m2 but in practice this has proved to
deliver excessive toxicity. Observational studies such as those of the NorthEastern German Society of Gynaecological Oncology have shown similar
tumour responses with 40mg/m2.
Cumulative Doses
Use with caution at cumulative doses in excess of 450mg/m2 (or equivalent
anthracycline dosage). Consider previous anthracycline exposure.
References
•
•
National Institute for Health and Clinical Excellence. Technology Appraisal 91. Paclitaxel, pegylated
liposomal doxorubicin hydrochloride and topotecan for second-line or subsequent treatment of
advanced ovarian cancer. [internet] accessed 09/12/2010, available at
http://www.nice.org.uk/nicemedia/live/11554/33024/33024.pdf
Rose PG. Pegylated liposomal doxorubicin: optimizing the dosing schedule in ovarain cancer. The
Oncologist. 2004;10 (3):205–14.
•
Sehouli J, Camara O, Schmidt M, Mahner S, Seipelt G, Otremba B, et al. North-Eastern German
Society of Gynecological Oncology. Pegylated liposomal doxorubicin (CAELYX®) in patients with
advanced ovarian cancer: results of a German multicenter observational study. Cancer Chemother
Pharmacol. 2009 64(3):585-91.
•
Daniels S. North London Cancer Network. Dose adjustment for cytotoxics in hepatic impairment
[internet]. accessed 09/12/2010 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 09/12/2010 available at http://www.bopawebsite.org/tikidownload_file.php?fileId=620
•
Summary of Product Characteristics Caelyx® (Pegylated Liposomal Doxorubicin Hydrochloride)
2mg/ml concentrate for solution for infusion (Schering-Plough) [internet], accessed 10/09/2010
available from http://www.medicines.org.uk/EMC/medicine/7017/SPC
•
Baxter K, editor. Stockley’s Drug Interactions. Pharmaceutical Press; 2009. Accessed on line on
09/12/2010 available at https://www.medicinescomplete.com/mc/
•
Trissel LA. Handbook of Injectable Drugs, 15th edition. American Society for Health-Systems
Pharmacists 2009. Accessed on line on 09/12/2010 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
Pegylated Liposomal Doxorubicin Hydrochloride PLDH (Caelyx ) chemotherapy for ovarian cancer
ASWCS09 GYN007
11/12/2011
Dr Paul Cornes, Consultant Oncologist, BHOC
Digitally signed by Paul Cornes
DN: cn=Paul Cornes, o=BHOC,
ou=Consultant Oncologist, email=james.
Jarrod Dunn, Cancer Services Pharmacist, TST
Checked by
James Carr, Network Pharmacist, ASWCS
James Carr
Authorised by
Jeremy Braybrooke, Chair, ASWCS Network
Chemotherapy Group
Review date
Document reviewed by
Version number
Summary of changes
December 2013
Jeremy
Braybrooke
Controlled document
Paul Cornes
[email protected], c=GB
Date: 2011.12.15 16:40:30 Z
Digitally signed by James Carr
DN: cn=James Carr, o=ASWCS, ou=Network
Pharmacist, [email protected],
c=GB
Date: 2011.12.15 16:40:59 Z
Digitally signed by Jeremy Braybrooke
DN: cn=Jeremy Braybrooke, o, ou,
[email protected], c=GB
Date: 2011.12.15 16:41:27 Z
1.1.a
Version
Document No
Version Number
ASWCS09 GYN007
1.1.a
Last printed 15/12/2011 16:39:00 *ONLY VALID ON DATE OF PRINTING*
Page 4 of 4