Download DA-EPOCH-R

DERBY-BURTON LOCAL CANCER NETWORK
FILENAME
DA-EPOCH_R.DOC
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CSIS Regimen Name:
DA_EPOCH_R
DA-EPOCH-R
Available for Routine Use in
Derby in-patient
Derby day-case
Derby community
Derby out-patient
Burton in-patient
Burton day-case
Burton community
Burton out-patient
Indication
Treatment Intent
Anti-Emetics
Frequency &
Duration

First line treatment of primary mediastinal B-cell lymphoma
Radical
Pre-chemotherapy
Day 1-5
3
Post-chemotherapy
A
Every 21 days for 6 to 8 cycles.
Restage after 4 and 6 cycles. If tumour masses shrink>20%
between cycles 4 and 6, continue for a further 2 cycles.
** DOSES FOR THE FIRST CYCLE (DOSE LEVEL 1) ARE SHOWN
BELOW. DOSES MAY BE ADJUSTED FROM CYCLE 2 BASED ON THE
PREVIOUS CYCLE’S NADIR (see haematological toxicity)**
Day 1
Allopurinol
300mg
Prednisolone
60 mg/m2
Paracetamol
1g
Chlorphenamine
10mg
Hydrocortisone
100mg
Rituximab
375mg/m2
Cotrimoxazole
Aciclovir
Fluconazole
Omeprazole
Metoclopramide
Ondansetron
480mg
400mg
50mg
20mg
10mg
8mg
DATE OF ISSUE: 25.08.16
REVIEWED BY: C.WARD
REVIEW DATE: 25.08.18
Oral once daily for 7 days for 1- 2
cycles. Consider pre-hydration with
IV fluids for bulky disease
Oral twice daily for 5 days (give 1st
dose 30 minutes pre rituximab)
Orally as a single dose 30 minutes
pre rituximab
Intravenous injection 30 minutes pre
rituximab
Intravenous injection 30 minutes pre
rituximab
Intravenous infusion in 500ml
sodium chloride 0.9% as per
rate calculator
Oral once daily for 21 days
Oral twice daily for 21 days
Oral once daily for 21 days
Oral once daily for 5 days
Oral four times daily as needed
Oral as a single dose prior to
chemotherapy, then twice daily as
needed
AUTHORISED BY: Dr J Addada
*** VALID ON DATE OF PRINTING ONLY ***
VERSION 2
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Ctd overleaf
2
Day 1-4 Doxorubicin
Vincristine
10 mg/m /day
0.4mg/m2/day
(no cap)
Day 1-4 Etoposide
50 mg/m2/day
Ondansetron
Day 5
8mg
Cyclophosphamide 750 mg/m
GCSF (Biosimilar)
Day 6
2
300
micrograms
Intravenous infusion in an
elastomeric infusor in sodium
chloride 0.9% via a central line over
96 hours
Intravenous infusion in 500ml sodium
chloride 0.9% over 24 hours via a
central line
Oral as a single dose prior to
chemotherapy
Intravenous bolus
Subcutaneous injection once daily
until neutrophil recovery (supply 7
doses)
Notes:



Doses are based on actual body weight and should not be routinely capped.
Consider omitting Rituximab in the first cycle if bulky disease.
Consider intrathecal prophylaxis for patients with >1 extranodal site and
elevated LDH
Rituximab
This section should be read in conjunction with the ‘Guidelines for the
administration of Rituximab’.
1. The day 1 dose of prednisolone should be given 30 mins prior to receiving
rituximab.
Premedication consisting of analgesia and an antihistamine and an intravenous
corticosteroid should always be administered 30 minutes before each infusion of
rituximab. (e.g. paracetamol 1g oral STAT and chlorphenamine 4mg oral or
10mg IV bolus STAT and hydrocortisone 100mg IV STAT). In addition pethidine
25mg IV should be available in case of a severe infusion reaction.
2. Rituximab doses should be rounded to the nearest 100mg.
Use rituximab rate calculator to assist with rate escalation of rituximab infusion.
3. Occurrence of an Infusion Related Event or Hypersensitivity:
Stop the infusion and contact a doctor.
When symptoms improve, continue the infusion at half the rate prior to the
reaction.
Accelerate the infusion rate more slowly as tolerated by the patient.
DATE OF ISSUE: 25.08.16
REVIEWED BY: C.WARD
REVIEW DATE: 25.08.18
AUTHORISED BY: Dr J Addada
*** VALID ON DATE OF PRINTING ONLY ***
VERSION 2
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Dose modifications and toxicities
1. Pre-treatment tests
FBC, U&Es, LFTs.
Urate, bone profile prior to 1st cycle and as clinically indicated. Patients at high
risk of tumour lysis refer to tumour lysis protocol.
Consider ECHO/MUGA to assess LV function in patients over 65 years or with
cardiac risk factors.
Double lumen central venous access required.
2. Haematological toxicity
Cycles should be repeated on day 22 provided the neutrophil count > 1x109/l
and the platelet count >75x109/l, otherwise repeat FBC daily until recoveryadminister filgrastim as necessary.
Patients with bone marrow involvement should be treated on time irrespective
of counts if safe to do so. Consider support with platelet transfusions.
Dose Adjustments according to nadir
Doxorubicin, Etoposide and Cyclophosphamide ONLY:
Doses may be adjusted from Cycle 2 based on the previous cycle’s neutrophil
(ANC) nadir. This is monitored by obtaining TWICE WEEKLY FBC, i.e. days 9,
12, 15,18:
 If nadir ANC ≥0.5x109/l: increase by 1 dose level
 If nadir ANC <0.5x109/l on 1 or 2 measurements: same dose as last
Cycle
 If nadir ANC <0.5x109/l on at least 3 measurements: decrease by 1 dose
level
 If platelet nadir <25x109/l: reduce by 1 dose level regardless of ANC
 Life threatening infections: decrease by 1 dose level
There is no maximum number of dose escalations.
Please see Table 1. overleaf:
DATE OF ISSUE: 25.08.16
REVIEWED BY: C.WARD
REVIEW DATE: 25.08.18
AUTHORISED BY: Dr J Addada
*** VALID ON DATE OF PRINTING ONLY ***
VERSION 2
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Table 1: Drug Dose Adjustments
Drugs
Drug Doses per Dose Levels
-2
-1
1
2
3
CYCLE 1
Prednisolone (mg/m2
twice daily)
Rituximab
2
(mg/m /day)
Doxorubicin
(mg/m2/day)
Vincristine
(mg/m2/day)
Etoposide
(mg/m2/day)
Cyclophosphamide
(mg/m2/day)
64%
(64%x0.8)
80%
(100%x0.8)
100%
(starting
dose)
120%
(100%x1.2)
144%
(120%x1.2)
60
60
60
60
60
375
375
375
375
375
10
10
10
12
14.4
0.4
0.4
0.4
0.4
0.4
50
50
50
60
72
480
600
750
900
1080
3. Non-haematological toxicity
Neurotoxicity:
If the patient complains of significant constipation or sensory loss in fingers
and/or toes, consider dose reduction of vincristine:
 Reduce by 25% for grade 2 motor neuropathy
 Reduce by 50% for grade 3 motor or sensory neuropathy
 For patients who develop ≥ grade 3 ileus, treatment should be delayed
until recovery and vincristine introduced at 75% of the normal dose
thereafter. If ≥ grade 3 ileus recurs, vincristine should be discontinued.
Infections:
Consider reducing by one dose level for life threatening infections associated
with organ failure or prolonged morbidity.
4. Renal impairment
Cyclophosphamide- clinical decision. Consider whether patient is being
treated with high dose.
Creatinine Clearance
Dose Modification
ml/min
10-20
75% dose of cyclophosphamide
<10
50% dose of cyclophosphamide
DATE OF ISSUE: 25.08.16
REVIEWED BY: C.WARD
REVIEW DATE: 25.08.18
AUTHORISED BY: Dr J Addada
*** VALID ON DATE OF PRINTING ONLY ***
VERSION 2
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Etoposide
Creatinine Clearance
ml/min
15-50
<15
Dose Modification
75% dose of etoposide
50% dose of etoposide
Doxorubicin
Clinical decision-discuss with Consultant if renal impairment severe.
Vincristine
No dose reduction required.
5. Hepatic impairment
Cyclophosphamide
No dose reductions are required for for hepatic impairment.
These are recommended doses although it should always be considered
whether liver impairment is disease related.
Doxorubicin
Bilirubin
micromol/L
20-51
51-85
>85
AST Units/L
2-3xULN
>3xULN
Etoposide
Bilirubin
micromol/L
26-51
>51
AST/ALT
Units/L
60-180
>180
DATE OF ISSUE: 25.08.16
REVIEWED BY: C.WARD
REVIEW DATE: 25.08.18
Dose Modification
50% dose of doxorubicin
25% dose of doxorubicin
omit
Dose Modification
75% dose
50% dose
Dose Modification
50% dose of etoposide
Clinical decision regarding further reduction of
etoposide
Dose Modification
50% dose of etoposide
Clinical decision regarding further reduction of
etoposide
AUTHORISED BY: Dr J Addada
*** VALID ON DATE OF PRINTING ONLY ***
VERSION 2
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FILENAME
DA-EPOCH_R.DOC
Vincristine
Bilirubin
micromol/L
26-51
>51
AST/ALT
Units/L
60-180
>180
HCCPG B52
CONTROLLED DOC NO:
CSIS Regimen Name:
DA_EPOCH_R
Dose Modification
50% dose of vincristine
50% dose of vincristine if AST/ALT normal, (if
AST/ALT>180 consider omission)
Dose Modification
50% dose of vincristine
Consider omission of vincristine
6. Drug Interactions
Itraconazole, posaconazole and voriconazole inhibit the metabolism of
vincristine increasing neurotoxicity, therefore are contraindicated.
Supportive care
1. Allopurinol 300mg once daily (100mg if creatinine clearance <20mls/min) for 12 cycles. Consider rasburicase for patients at high risk of tumour lysis. Refer to
tumour lysis protocol.
2. Co-trimoxazole 480mg once daily. In cases of allergy to co-trimoxazole,
consider dapsone 100mg daily.
3.
4.
5.
6.
7.
Aciclovir 400mg twice daily.
Fluconazole 50mg daily.
Omeprazole 20mg once daily for 5 days (i.e. concurrently with prednisolone)
All patients receive primary prophylaxis with GCSF (filgrastim).
Consider mesna if high dose cyclophosphamide prescribed on dose escalation
(>1.5g/m2)
References
1. Dunleavy D, et al. Dose-Adjusted EPOCH-Rituximab Therapy in Primary
Mediastinal B-Cell Lymphoma. N Engl J Med 2013; 368:1408-16.
2. The North London Cancer Network- Dose Adjustment for Cytotoxics in Renal
Impairment. Jan 2009
3. The North London Cancer Network- Dose Adjustment for Cytotoxics in Hepatic
Impairment. Jan 2009
4. SPC Vincristine accessed online on 18/9/15 at www.medicines.org.uk
DATE OF ISSUE: 25.08.16
REVIEWED BY: C.WARD
REVIEW DATE: 25.08.18
AUTHORISED BY: Dr J Addada
*** VALID ON DATE OF PRINTING ONLY ***
VERSION 2
PAGE 6 of 6