Download Regimen: Vinorelbine (Oral) for Advanced Breast Cancer

Regimen:
Indication
Regimen detail
Administration
Frequency
Vinorelbine (Oral) for Advanced Breast Cancer
NICE approved for the treatment of advanced breast cancer where initial
cytotoxic chemotherapy (including anthracycline) has failed or is
inappropriate.
Days
1&8
Drug
Vinorelbine
Dose
60mg/m2 (Cycle 1, Days 1 & 8 and
Cycle 2, Day 1)
Oral
80mg/m2 (Cycle 2, Day 8 onwards if
nadir neutrophil count >0.5 x 109/l and
no neutropenic sepsis)*
*For any administration planned to be given at 80mg/m², if the neutrophil
count is below 500/mm3 or more than once between 500 and 1000 / mm3
the administration should be delayed until recovery and the dose reduced
from 80 to 60mg/m2 per week during the 3 following administrations.
The dose may be re-escalated from 60 to 80 mg/m2 per week if the
neutrophil count did not drop below 500/mm3 or more than once between
500 and 1000/mm3 during 3 administrations given at 60 mg/m2.
Available as 20mg, 30mg and 80mg capsules.
Vinorelbine should be swallowed with cold water without chewing or
sucking the capsule. It is recommended to take the capsule with some
food.
Recommended doses are:
80mg/ m2
60mg/m2
Body surface area
Dose (mg)
Dose (mg)
1.25-1.34
80
100
1.35-1.44
80
110
1.45-1.54
90
120
1.55-1.64
100
130
1.65-1.74
100
140
1.75-1.84
110
140
1.85-1.94
110
150
>1.95
120
160
Every 21 days
Usual maximum 6 cycles
Vinorelbine may also be given weekly for 3 weeks out of 4 (i.e. on days 1,
8 & 15 every 28 days)
Extravasation
Not applicable
Premedication
None required
Emetogenicity
Moderate-high emetic potential – refer to local protocol
NB: In the case of vomiting within a few hours after drug intake,
Controlled document
Route
Oral
Document No
Version Number
ASWCS09 BR014
1.1.a
Last printed 03/12/2010 *ONLY VALID ON DATE OF PRINTING*
Page 1 of 4
Additional recommended
supportive medication
administration of this dose should NOT be repeated.
H2 antagonist or Proton Pump Inhibitor if required
Pre- treatment evaluation
FBC
LFT
U&E (inc. SrCr)
Regular investigation
FBC
Pre D1 – results valid for 72 hours
LFT
Pre D1 – results valid for 96 hours
U&E (inc. SrCr) Pre D1 – results valid for 96 hours
Clinical
Clinically assess patient prior to each cycle,
Assessment
particularly focusing on whether the patient has
developed neuropathy and gastrointestinal toxicity.
Evaluate response at least every 3 cycles.
Standard limits for
administration to go
ahead – if blood results not
Neutrophil count
Platelet count
Bilirubin
ALT / AST
within range, authorisation to
administer must be given by
prescriber/consultant
Baseline - results valid for 14 days
Baseline - results valid for 14 days
Baseline - results valid for 14 days
≥1.5 x 109/l
≥100 x 109/l
≤1.5 x ULN
≤ 1.5 x ULN
Dose modifications
•
Haematological
toxicity
Day 1: If neutrophils <1.5 x 109/l and/or platelets <100 x 109/l delay 1
week or until count recovery.
Day 8: If neutrophils <1.0 x 109/l and/or platelets <75 x 109/l delay 1 week
or until count recovery.
•
Renal impairment
No dose adjustment for renal impairment
•
Hepatic
impairment
AST +/or ALT
1.5 -2.5 x ULN and/or
Any and
Any and
Bilirubin
≤ 1.5 x ULN
1.5 – 3 x ULN
> 3 x ULN
Vinorelbine dose
60mg/m2
50mg/m2
Discontinue
If liver toxicity persists for more than 3 weeks then discontinue treatment.
•
NCI Common
Toxicity Criteria
Toxicity
Febrile
neutropenia
Definition
ANC <0.5 x
109/l plus
fever requiring
IV antibiotics
+/hospitalisation
Peripheral
neuropathy
Grade 2
Constipation
Controlled document
≥ Grade 3
≥ Grade 3
Dose adjustment
1st episode reduce vinorelbine dose
back to 60mg/m2 (or to 50mg/m2 if
already on 60mg/m2)
2nd episode reduce vinorelbine dose
to 50mg/m2 and omit day 8 in
subsequent cycles
Once febrile neutropenia has
occurred, doses should NOT be reescalated.
Reduce vinorelbine back to 60mg/m2
(or to 50mg/m2 if already on 60mg/m2)
Discuss with consultant
Reduce vinorelbine back to 60mg/m2
(or to 50mg/m2 if already on 60mg/m2)
Document No
Version Number
ASWCS09 BR014
1.1.a
Last printed 03/12/2010 *ONLY VALID ON DATE OF PRINTING*
Page 2 of 4
Other
toxicities
Adverse effects – the
contents of the table indicate the
adverse effects that should be
documented on consent to
treatment forms
≥ Grade 3
toxicity (except
alopecia)
Rare or Serious Side Effects
Febrile neutropenia
Myelosuppression
Risk of second malignancy e.g.
leukaemia
Teratogenicity
Long term risk of early
menopause, reduced fertility
Peripheral neuropathy
Systemic allergic reactions
including anaphylaxis
Ischaemic heart disease
Significant drug
interactions –
For full details consult product
literature/ reference texts
Defer therapy for 1 week until
resolved to ≤ grade 1. Discuss with
consultant if >1 week delay
Frequently occurring Side Effects
Nausea and vomiting
Constipation
Stomatitis and mucositis
Myalgia
Fatigue
Peripheral neuropathy
Bronchospasm
Mild alopecia
Other side effects include: SIADH, hyponatraemia, hypotension
Vaccines – Vinorelbine is contra-indicated with yellow fever and should
also not be given with other live attenuated vaccines
Enzyme inducers/inhibitors - in vitro studies suggest that CYP3A4
inhibitors (such as ketoconazole and erythromycin) will raise vinorelbine
levels, whereas CYP3A inducers (such as rifampicin and barbiturates) will
reduce vinorelbine levels.
Anticoagulants - the frequency of monitoring the INR should be
increased due to the potential interaction with oral anticoagulants and
increased variability of coagulation in patients with cancer.
Comments
Cumulative Doses
None
References
• National Institute of Health and Clinical Excellence Guideline CG81.
Advanced Breast Cancer: Diagnosis and Treatment February 2009.
Accessed online on 21/05/2009 available at
http://www.nice.org.uk/nicemedia/pdf/CG81FullGuideline.pdf
• Daniels S. North London Cancer Network. Dose adjustment for
cytotoxics in hepatic impairment [internet]. accessed 21/05/2009
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 21/05/2009
available at http://www.bopawebsite.org/tikidownload_file.php?fileId=620
• 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.
Controlled document
Document No
Version Number
ASWCS09 BR014
1.1.a
Last printed 03/12/2010 *ONLY VALID ON DATE OF PRINTING*
Page 3 of 4
•
Document title
Document number
Approval date
Written by
Checked by
Authorised by
Review date
Document reviewed by
Version number
Summary of changes
Controlled document
Summary of Product Characteristics Navelbine (Vinorelbine)
30mg soft capsule (Pierre Fabre) [internet] accessed 01/09/2010
available from http://www.medicines.org.uk/EMC/medicine/1604
Vinorelbine (oral) for Breast Cancer
ASWCS09 BR014
15/10/2010
Jeremy Braybrooke, Consultant Medical Oncologist,
BHOC, and Chair, ASWCS Drugs and Therapeutics
Committee
Becky Bagnall, Consultant Pharmacist, NBT
Jeremy Braybrooke, Chair ASWCS Drugs and
Therapeutics Committee
15/10/2011
Jeremy
Braybrooke
Becky Bagnall
Jeremy
Braybrooke
Digitally signed by Jeremy Braybrooke
DN: cn=Jeremy Braybrooke, o, ou,
[email protected], c=GB
Date: 2010.12.03 13:10:27 Z
Digitally signed by Becky Bagnall
DN: cn=Becky Bagnall, o, ou, [email protected].
uk, c=GB
Date: 2010.12.03 13:11:18 Z
Digitally signed by Jeremy Braybrooke
DN: cn=Jeremy Braybrooke, o, ou,
[email protected], c=GB
Date: 2010.12.03 13:10:48 Z
1.1.a
Version
Document No
Version Number
ASWCS09 BR014
1.1.a
Last printed 03/12/2010 *ONLY VALID ON DATE OF PRINTING*
Page 4 of 4