Download Regimen: Paclitaxel weekly for Breast Cancer

Regimen: Paclitaxel weekly for Breast Cancer
Indication
Treatment of advanced breast cancer where initial cytotoxic
chemotherapy (including anthracycline) has failed or is inappropriate.
Regimen detail
Day
Drug
Dose
Route
1,8,15 Paclitaxel
80mg/m2 *
IV
*dose may vary from 70-100mg/m2 depending on patient status
Administration
Paclitaxel is administered in 250-500ml sodium chloride 0.9% via nonPVC infusion bag with a 0.22 micron in-line filter. Paclitaxel should be
diluted to a concentration 0.3-1.2mg/ml.
Paclitaxel is administered over 1 hour
Frequency
Every 21 days for 6 cycles (i.e. weekly for a total of 18 doses)
Extravasation
Paclitaxel is a vesicant
Premedication
Paclitaxel can cause a severe allergic reaction due to the drug carrier.
Therefore patients should receive the following pre-medication prior to
each paclitaxel dose
Drug
Dexamethasone
Emetogenicity
Additional
recommended
supportive medication
Dose
8mg
Route
IV
Administration
30-60 minutes prior to
paclitaxel infusion
Chlorphenamine 10mg IV
30-60 minutes prior to
paclitaxel infusion over at least
1 minute
Ranitidine
50mg IV
30-60 minutes prior to
paclitaxel infusion over at least
2 minutes
This regimen has moderate emetic potential – refer to local protocol
Mouthwashes as per local policy
H2 antagonist or PPI if required
Pre- treatment
evaluation
FBC
LFT
U&E
Baseline - results valid for 2 weeks
Baseline - results valid for 2 weeks
Baseline - results valid for 2 weeks
Regular investigation
FBC
LFT
D1, 8 and 15 – results valid for 24 hours
Pre D1 – results valid for 72 hours (do weekly LFTs if
raised at baseline)
Pre D1 – results valid for 72 hours
U&E
Controlled document
Document No
Version Number
ASWCS09 BR011
1.1.a
Last printed 03/12/2010 *ONLY VALID ON DATE OF PRINTING*
Page 1 of 3
Standard limits for
administration to go
ahead – if blood results not
within range, authorisation to
administer must be given by
prescriber/consultant
Neutrophil count
Platelet count
Creatinine Clearance
Bilirubin
≥1.0 x 109/l
≥100 x 109/l
≥ 20ml/min
≤1.5 x ULN
Dose modifications
•
9
9
Haematological Day 1: If neutrophils <1.0 x 10 /l and/or platelets <100 x 10 /l delay 1
week, then resume at 100% dose. If > 1 week for recovery discuss with
toxicity
consultant.
•
Renal
impairment
No dose adjustment for renal impairment
•
Hepatic
impairment
Paclitaxel is not recommended in severe hepatic impairment. A dose
reduction should be given initially if hepatic function impaired at baseline
(bilirubin > 26 micromol/L). For more severe impairment, treatment may
proceed at reduced dose, at consultant’s discretion, and with weekly
monitoring of LFTs.
•
NCI Common
Toxicity
Criteria
Toxicity
Febrile
neutropenia
Definition
ANC <0.5 x 109/l
plus fever requiring
IV antibiotics +/hospitalisation
Dose adjustment
Reduce paclitaxel to 80% for
subsequent cycles. Recommend
prophylactic ciprofloxacin 250mg
bd for 7 days starting day 5
Peripheral
neuropathy
Grade 2
Reduce paclitaxel to 65mg/m2
≥ grade 3
≥ grade 3 toxicity
(except alopecia)
Omit paclitaxel
Defer therapy for 1 week until
resolved to ≤ grade 1. Discuss
with consultant if >1 week delay
Other
toxicities
Adverse effects – the
contents of the table indicate
the adverse effects that
should be documented on
consent to treatment forms
Rare or Serious Side Effects
Febrile neutropenia
Myelosuppression
Risk of second malignancy e.g.
leukaemia
Infusion related reaction
Teratogenicity
Long term risk of early
menopause, reduced fertility
Frequently occurring Side Effects
Nausea and vomiting
Alopecia
Stomatitis and mucositis
Peripheral neuropathy
Diarrhoea
Fatigue
Sore veins
Other side effects include: myalgia, arthralgia, taste changes, headaches,
abdominal pain, bradycardia, low blood pressure, altered liver function.
Significant drug
interactions –
Controlled document
Warfarin/courmarin anticoagulants Avoid use – switch patients to low
molecular weight heparin during treatment – elevations in INR.
Document No
Version Number
ASWCS09 BR011
1.1.a
Last printed 03/12/2010 *ONLY VALID ON DATE OF PRINTING*
Page 2 of 3
For full details consult
product literature/ reference
texts
Enzyme inducers/inhibitors – Concomitant administration of inducers or
inhibitors of cytochrome P450 isoenzymes (CYP2C8 and 3A4) e.g.
erythromycin, fluoxetine, gemfibrozil, rifampicin, carbamazepine,
phenytoin, phenobarbital etc, may alter the pharmacokinetics of paclitaxel
presenting a theoretical interaction.
Comments
Cumulative Doses
None
References
Peretz T, Sulkes A, Chollet P, Gelmon K, Paridaens R, Gorbonuva V, et al (1999) A multicenter,
randomized study of two schedules of paclitaxel (PXT) in patients with advanced breast cancer.(ABC)
Eur J Cancer. 31A (Supplement 5): S75.
Seidman AD, Hudis CA, Albanel J, Tong W, Tepler I, Currie V, et al. (1998) Dose-dense therapy with
weekly 1-hour paclitaxel infusions in the treatment of metastatic breast cancer. J Clin Oncol. 16: 335361.
Daniels S. North London Cancer Network. Dose adjustment for cytotoxics in hepatic impairment
[internet]. accessed 21/09/2010 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 21/09/2010 available at http://www.bopawebsite.org/tikidownload_file.php?fileId=620
Summary of Product Characteristics Paclitaxel 6mg/ml concentrate for solution for infusion (Hospira)
[internet], accessed 21/09/2010 available from
http://www.medicines.org.uk/EMC/medicine/15842/SPC/Paclitaxel+6+mg+ml++concentrate+for+soluti
on+for+infusion+(Hospira+UK+Ltd)
Baxter K, editor. Stockley’s Drug Interactions. Pharmaceutical Press; 2009. Accessed on line on
21/09/2010 available at https://www.medicinescomplete.com/mc/
th
Trissel LA. Handbook of Injectable Drugs, 15 edition. American Society for Health-Systems
Pharmacists 2009. Accessed on line on 21/09/2010 available at
http://www.medicinescomplete.com/mc/hid/current/
th
Allwood M, Stanley A, Wright P, editors. The cytotoxics handbook. 4 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
Paclitaxel weekly for Breast Cancer
ASWCS09 BR011
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 12:33:38 Z
Digitally signed by Becky Bagnall
DN: cn=Becky Bagnall, o, ou, [email protected],
c=GB
Date: 2010.12.03 12:33:16 Z
Digitally signed by Jeremy Braybrooke
DN: cn=Jeremy Braybrooke, o, ou,
[email protected], c=GB
Date: 2010.12.03 12:33:57 Z
1.1.a
Version
Document No
Version Number
ASWCS09 BR011
1.1.a
Last printed 03/12/2010 *ONLY VALID ON DATE OF PRINTING*
Page 3 of 3