Download 2.27 R-Fludarabine version1.2 Jul08

2.27 Protocol Name:
Rituximab-Fludarabine
Indications
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Advanced stage indolent and follicular lymphoma
(especially useful for diabetic patients in whom the clinician
wishes to avoid steroids)
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 contra indication 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.
Rituximab has been associated with potentially serious
Hepatitis ‘flare’ in patients with chronic hepatitis B infection.
All patients should have hepatitis B serology checked
before therapy, and in those who have positive serology
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lamivudine 100mg daily should be commenced 1-2 weeks
prior to rituximab. Currently it is recommended that
lamivudine is continued for 6 months after rituximab is
discontinued.
Drug Regimen
(OPCS code: X70.4)
Days
1
Drug
Rituximab
Dose
375mg/m²
Route
IV
Comments
See below for infusion speed
1–5
Fludarabine
40mg/ m²
PO
Once daily after breakfast
Rituximab infusion speed:
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First infusion: Initiate at 50mg/h; if tolerated increase rate
at 50mg/h increments every 30 minutes to a maximum of
400mg/h.
Subsequent infusions: Initiate at 100 mg/h; if tolerated
increase rate at 100mg/h increments every 30 minutes to a
maximum of 400 mg/h.
Fast rate infusion: Many units have implemented this
locally as a safe method of reducing the infusion time
Patients MUST have tolerated their first cycle of rituximab
(at the standard recommended infusion rates as specified
above) before being given the rapid infusion rate.
All rituximab doses are prepared in 250mls 0.9% sodium
chloride, with 50mls being given over the first 30 minutes
and the remaining 200mls given over 1 hour.
If a 500ml volume of 0.9% sodium chloride is used, then
100mls is given over the first 30 minutes and the remaining
400mls given over 1 hour.
Considerations
Oral fludarabine is only available as 10mg tablets so round doses
up or down to the nearest whole tablet.
Cycle Frequency
Repeat every 28 days.
Dose Modifications
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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 dose reductions:
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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 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.
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 5.
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 six months
after completion of chemotherapy.
Consider Acyclovir 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: **
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References
SPC
Patient Information
http://www.cancerbackup.org.uk/Treatments/Chemotherapy/Individualdrugs/Fludarabi
ne
http://www.cancerbackup.org.uk/Treatments/Biologicaltherapies/Monoclonalantibodies
/Rituximab
Written by:
Dr Ed Kanfer
Authorised by:
WLCN Haematology TWG
Date for review by Haematology TWG:
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