2
nd
Docetaxel Single Agent
line in oesophago-gastric adenocarcinoma
(Palliative)
Background: Single agent docetaxel has demonstrated an overall survival
advantage over best supportive care in selected patients with
adenocarcinoma of the oesophagus, oesophago-gastric junction or stomach
who have progressed on or relapsed within 6 months of first line
chemotherapy (COUGAR-02 Trial).
Patient Group:
For patients with advanced, histologically confirmed adenocarcinoma of the
oesophagus, oesophago-gastric junction, or stomach that has progressed on
or within 6 months of treatment with platinum/fluoropyrimidine combination
chemotherapy.
PS 0-2
Pre-treatment Assessment:
Weight, FBC, U&E, LFTs and Creatinine clearance
CT/MRI scan
Treatment Threshold
WBC ≥ 3 x 109/L
ANC ≥ 1.5 x 109/L
Platelets ≥ 150 x109/L
AST or ALT < 1.5 x ULN
Bilirubin < 22µmol/L
Regimen Details:
Day 1
Docetaxel 75mg/M2 in 500mL sodium chloride 0.9% IV infusion over 60
minutes.
Checked by:
Gwenda Duffy
Authorised by:
Dr D Wilkins
Date:
April 14
Protocol No. 625
Version No. 1
**CONTROLLED DOCUMENT- ONLY VALID ON DATE OF PRINTING**
Page
Written by:
Tracy Parry-Jones
1
Repeated every 3 weeks for 4-6 cycles
Administration: Patients should be observed closely for hypersensitivity
reactions especially during the first and second infusions. Hypersensitivity
reactions may occur within a few minutes following the initiation of the infusion
of docetaxel, thus facilities for the treatment of hypotension and
bronchospasm should be available. If hypersensitivity reactions occur, minor
symptoms such as flushing or localized cutaneous reactions do not require
interruption of therapy. However, severe reactions, such as severe
hypotension, bronchospasm or generalised rash/erythema require immediate
discontinuation of docetaxel and appropriate therapy. Patients who have
developed severe hypersensitivity reactions should not be re-challenged with
docetaxel
Pre-medication: Dexamethasone 8mg PO BD for 3 days starting the day
before chemotherapy.
Ondansetron 8mg IV or PO 30 minutes prior to chemotherapy.
Anti-emetics: Highly emetogenic.
Monitoring and Assessment:
Clinical Assessment
FBC – prior to each cycle
U&E, LFT creatinine clearance (calculated) – prior to each cycle
CT/MRI scan post 3 cycles to assess response to treatment.
Dose Modifications:
Haematological toxicity
Neutrophils < 1.5 x 109/L
Platelets
< 150 x 109/L
defer dose
defer dose
In patients who experienced either febrile neutropenia, neutrophil < 0.5 x
109/L for more than one week, severe or cumulative cutaneous reactions or
severe peripheral neuropathy during docetaxel therapy, the dose of docetaxel
should be reduced from 75 to 55mg/m². If the patient continues to experience
these reactions at 55mg/m², the treatment should be discontinued. GCSF use
is not indicated.
Non Haematological Toxicity (Excluding Alopecia)
Checked by:
Gwenda Duffy
Authorised by:
Dr D Wilkins
Date:
April 14
Protocol No. 625
Version No. 1
**CONTROLLED DOCUMENT- ONLY VALID ON DATE OF PRINTING**
Page
Written by:
Tracy Parry-Jones
2
For toxicities of up to grade 2- delay treatment by one or more weeks until
recovery to grade 0 or 1.
For severe or cumulative cutaneous reactions or severe peripheral
neuropathy during docetaxel therapy, the dose of docetaxel should be
reduced from 75 to 55mg/m2.
For other grade 3 or 4 non-haematological toxicities docetaxel should be
reduced from 75 to 55 mg/m2. If the patient continues to experience these
reactions the treatment should be discontinued
Renal impairment
No dose modification required.
Hepatic Impairment
AST or ALT > 1.5 x upper limit normal Reduce dose of Docetaxel by 25%
If Bilirubin >22µmol/L +/or ALT/AST >3.5 ULN with ALP >6 x ULN, docetaxel
should not be used unless strictly indicated.
Final concentration of 0.74mg/mL docetaxel should not be exceeded.
•
Clinically significant interactions which induce, inhibit or are
metabolised by cytochrome P450-3A, include: ciclosporin, terfenadine,
ketoconazole, erythromycin and troleandomycin.
Most Common Toxicities:
• Alopecia
• Neutropenia +/- infection
• Fatigue
• Sensory neuropathy
• Skin reaction (May be severe)
• Oedema
• Mucositis
• Diarrhea
• Nausea and Vomiting
• Fever
• Nail disorder
• Hypersensitivity (May be severe)
• Myalgia and arthralgia
• Motor neuropathy
• ↑ LFTs
• Pain
• Eye disorders /Watering eyes
Written by:
Tracy Parry-Jones
Checked by:
Gwenda Duffy
Authorised by:
Dr D Wilkins
Date:
April 14
Protocol No. 625
Version No. 1
**CONTROLLED DOCUMENT- ONLY VALID ON DATE OF PRINTING**
Page
•
3
Pharmaceutical Care:
References:
1. SPC Docetaxel 20mg/mL concentrate for solution for infusion Actavis.
Actavis UK Ltd. www.medicines.org.uk [accessed 12th March 2014]
2. H E R Ford et al Docetaxel versus active symptom control for refractory
oesophagogastric adenocarcinoma (COUGAR-02):an open-label,
phase 3 randomised controlled trial Lancet Oncology 2014; 15: 78–86
Checked by:
Gwenda Duffy
Authorised by:
Dr D Wilkins
Date:
April 14
Protocol No. 625
Version No. 1
**CONTROLLED DOCUMENT- ONLY VALID ON DATE OF PRINTING**
Page
Written by:
Tracy Parry-Jones
4
3. North London Cancer Network guidelines for dosage adjustment for
cytotoxics in renal and hepatic impairment. NLCN 2009.