Download 2.05 Fludarabine Version 2.3

West London Cancer Network
2.05 Protocol Name:
Fludarabine (single agent)
Indications
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CLL (NICE TAG No. 119, February 2007)
Mantle Cell lymphoma
Advanced stage indolent and follicular lymphoma
Pre-treatment Evaluation
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Document histological sub-type of lymphoproliferative disorder according
to WHO Classification.
Document FBC (with film), U&E, creatinine, LFTs, calcium, glucose,
serum protein electrophoresis, immunoglobulin levels and a direct
antiglobulin test (DAT).
If staging is relevant this should include documentation of B symptoms,
CT of chest, abdomen & pelvis and bone marrow aspirate & trephine.
Document WHO performance status of patient.
A positive DAT is a relative contraindication to fludarabine therapy
Document height, weight and body surface area.
Consider ECG ± echocardiogram if clinical suspicion of cardiac
dysfunction.
Give adequate verbal and written information for patients and relatives
concerning patient’s disease, treatment strategy and side effects.
Obtain written consent from patient or guardian.
If appropriate, discuss the possibility of pregnancy with female patients
of child-bearing age and the need for contraception with both male and
female patients.
If appropriate, discuss potential risk of infertility with patient and
relatives.
Consider intravenous hydration in patients with bulk disease.
Allopurinol should be given for the first 2 cycles of chemotherapy.
Significant pleural effusions or ascites should be drained to a minimum
prior to commencement of fludarabine.
All cellular blood components should be irradiated to prevent the
rare occurrence of transfusion associated graft versus host
disease.
Caution- patients with a positive DAT/ AIHA
- Patients with a positive DAT without haemolysis must be monitored closely
throughout treatment.
- Haemolysis on fludarabine is a contraindication to further treatment with this agent.
- Patients haemolysing before treatment should be treated with steroids / before
initiating chemotherapy. If haemolysis is mild, use 2 to 3 weeks of steroids.
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West London Cancer Network
Drug Regimen
(OPCS code: X70.5)
Days
Drug
Dose
Route
Comments
1-5
Fludarabine
25mg/m²
IV
Intravenous bolus in 10-100mls 0.9%
saline over 15-30 minutes
Alternative ORAL schedule
(OPCS code: X70.4)
Days
Drug
Dose
Route
Comments
1–5
Fludarabine
40mg/ m² *
PO
Once daily after breakfast
* appropriate rounding to available tablet size (fludarabine 10mg tablets)
Cycle Frequency
Repeat every 28 days
Dose Modifications
Renal impairment:
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Reduce by up to 50% doses if renal impairment
(creatinine clearance between 30-60ml/min).
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Do not give if creatinine clearance <30ml/min.
Haematological toxicity:
Patients with good prognosis - consider maintaining dose intensity with GSCF.
GCSF should be administered in doses sufficient to allow full dose of treatment on
schedule. However use of GCSF should be in accordance with the local protocol/
ASCO guidance – therefore only for maintenance of full dose after an episode of
febrile neutropenia or prolonged neutropenia that has led to a dose reduction.
Neutropenia and thrombocytopenia may be due to disease.
If a fall in counts is considered to be due to treatment (and GCSF is not
appropriate) then, the following guidelines should be followed.
- At the time of the next cycle: If neutrophils <1 x 109/l or platelets <75 x 109/l,
delay treatment for 1 week.
- If these values are not improved after a delay of 2 weeks treatment should
proceed at 50% of the dose.
- If neutrophils are below 0.5 x 109/l or platelets below 50 x 109/l by the time a
new course is due, delay treatment until counts rise to at least these levels, with
dose modifications as above if necessary.
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West London Cancer Network
Investigations prior to subsequent cycles
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FBC, U+E, Creat and LFTs
Clinical assessment of response to be documented in notes
Assuming clinical response, restage after cycle 3 and again after cycle 6
Treatment Duration
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Maximum 6 cycles
Concurrent Medication
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Allopurinol 300mg od PO (100mg if creatinine clearance <20mls/min) for
first 2 cycles
Oral systemic PCP prophylaxis should be given according to local
protocol throughout treatment and for 6 months after completion of
chemotherapy
Consider aciclovir antiviral prophylaxis if previous history of VZV or HSV
reactivation
Anti-emetics
This regimen has mild emetic potential - refer to local protocol.
** Issue patient with DOH/National Blood Service Irradiated Blood Products
information sheet: **
References
MRC CLL4 Trial
NICE Technology Appraisal Guidance No. 119, February 2007
Patient information
http://www.macmillan.org.uk/Cancerinformation/Cancertreatment/Treatmenttypes/Che
motherapy/Individualdrugs/Fludarabine.aspx
Written by: Dr G Hughes, Dr E Kanfer, Dr D Macdonald, Dr M Sekhar and Melanie Schenck
Revised by: Sasha Marks and Stephanie Kirschke, September 2009
Authorised by:
WLCN Haematology TWG, September 2009
Date for review by Haematology TWG: September 2010
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