DERBY-BURTON LOCAL CANCER NETWORK
FILENAME
R-ICE
HCCPG B55
CONTROLLED DOC NO:
CSIS Regimen Name:
R-ICE
R-ICE Regimen- Rituximab, Etoposide, Ifosfamide (with
MESNA), Carboplatin (+ Depocyte® if CNS involvement)
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
Day 1
Day 2

Relapsed DLBCL /DLBCL with CNS involvement
Radical
Pre-chemotherapy
3
Post-chemotherapy
A
Every 21 days(or upon recovery of bone marrow).
For up to 3 cycles after completion of 3 cycles of MATRIX
chemotherapy if used in this combination.
Allopurinol
Paracetamol
300mg
1g
Chlorphenamine
10mg
Hydrocortisone
100mg
Rituximab
375mg/m2
Etoposide
100mg/m2
Phenytoin
Aciclovir
300mg
400mg
Cotrimoxazole
480mg
Metoclopramide
Sodium chloride
0.9%
Sodium chloride
0.9%
10mg
1 litre
Oral once daily for 14 days
As a single oral dose 30 minutes prior to
rituximab
As a single intravenous dose 30 minutes
prior to rituximab
As a single intravenous dose 30 minutes
prior to rituximab
Intravenous infusion in 500ml 0.9%
sodium chloride
Intravenous infusion in 500ml-1000ml
sodium chloride 0.9% over 60 mins (max
conc. 0.4mg/ml)
Oral once daily at night for 6 days
Oral twice daily until lymphocytes >1 x
109/l
Oral Once daily until lymphocytes >1 x
109/l
Oral four times daily as required
Intravenous infusion over 6 hours
1 litre
Intravenous infusion over 6 hours
Dexamethasone
8mg
As a single oral or intravenous dose prior
to chemotherapy
DATE OF ISSUE 06.03.17
REVIEWED BY K.GRAHAM
/ C.WARD
REVIEW DATE 06.03.19
VERSION 3
AUTHORISED BY: Dr J Addada
*** VALID ON DATE OF PRINTING ONLY ***
PAGE 1 of 6
DERBY-BURTON LOCAL CANCER NETWORK
FILENAME
Day 3
Day 4
Day 6
Day 6
R-ICE
HCCPG B55
CONTROLLED DOC NO:
CSIS Regimen Name:
R-ICE
Etoposide
100mg/m2
Carboplatin
Mesna
AUC=5
5x(25+CrCl)
(max 800mg)
1000mg/m2
Ifosfamide &
Mesna
5000mg/m2
2
5000mg/m
Etoposide
100mg/m2
Mesna
3000mg/m2
Dexamethasone
4mg
Only if CNS involvement:
Liposomal
50mg
cytarabine
(Depocyte®)
G-CSF
300
(Filgrastim)
micrograms
(non-mobilising
cycles)
OR
Lenograstim
263
(stem cell
micrograms if
mobilising
BSA <1.8m2,
cycles)
368
micrograms if
BSA ≥ 1.8m2
DATE OF ISSUE 06.03.17
REVIEWED BY K.GRAHAM
/ C.WARD
REVIEW DATE 06.03.19
Intravenous infusion in 500ml-1000ml
sodium chloride 0.9% over 60 mins (max
conc. 0.4mg/ml)
Intravenous infusion in 500ml 5%
glucose over 1 hour
Intravenous infusion in 100ml sodium
chloride 0.9% over 15 minutes
immediately before Ifosfamide and
Mesna infusion
Intravenous infusion in 2000ml sodium
chloride 0.9% (2 x 1000ml infusion bags)
over 24 hours
Intravenous infusion in 500ml-1000ml
sodium chloride 0.9% over 60 mins (max
conc. 0.4mg/ml)
Intravenous infusion in 1000ml dextrose
4% & sodium chloride 0.18% over 12
hours immediately after the end of
Ifosfamide and Mesna infusion
Oral twice daily for 6 days (if having
Depocyte®) or for 2 days otherwise
Intrathecal injection- prescribe on a
separate intrathecal chart
Subcutaneous injection ONCE daily until
neutrophils > 1.0 x 109/L (supply 8
doses)
Subcutaneous injection ONCE daily until
adequate stem cell collection (supply 7
doses)
VERSION 3
AUTHORISED BY: Dr J Addada
*** VALID ON DATE OF PRINTING ONLY ***
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DERBY-BURTON LOCAL CANCER NETWORK
FILENAME
R-ICE
HCCPG B55
CONTROLLED DOC NO:
CSIS Regimen Name:
R-ICE
Notes:
Pre-treatment investigations
FBC, U&Es, LFTs, CrCl (ideally by measured Cr-EDTA prior to 1st cycle)
It is recommended that patients receive pre-hydration with 2 litres of sodium
chloride 0.9% over 12 hours.
Assess response after the 1st and 3rd cycle and review treatment plan if stable or
progressive disease.
Rituximab
This section should be read in conjunction with the ‘Guidelines for the
administration of Rituximab’.
1. 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.
Dose modifications and toxicities
1. Haematological toxicity
Delay treatment until neutrophils > 1 x109/l and platelets > 100x109/l unless
cytopenias are considered to be disease-related.
The dose of chemotherapy will be determined according to the nadir neutrophil
or platelet counts of the previous course as follows:
Nadir
neutrophils
3
R-ICE dose
Nadir platelets
3
R-ICE dose
3
(x10 /mm )
3
(x10 /mm )
<0.5
75% dose of
ifosfamide
if
complicated with
infection
DATE OF ISSUE 06.03.17
REVIEWED BY K.GRAHAM
/ C.WARD
REVIEW DATE 06.03.19
< 25
75% dose of
ifosfamide if
complicated with
bleeding
VERSION 3
AUTHORISED BY: Dr J Addada
*** VALID ON DATE OF PRINTING ONLY ***
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DERBY-BURTON LOCAL CANCER NETWORK
FILENAME
R-ICE
HCCPG B55
CONTROLLED DOC NO:
CSIS Regimen Name:
R-ICE
2. Non-haematological toxicity
For CTCAE grade 2 or less non-hematological toxicity, no dose reductions will
be required. For CTC (version 4.03) grade 3-4 non-hematological toxicity, the
total dose of etoposide, carboplatin and ifosfamide to be administered for the
next course will be reduced as follows:
Toxicity
Grade 3
Grade 4
Cardiovascular
Coagulation
Gastrointestinal
Renal
Hepatic
Pulmonary
Interruption
Unchanged
Unchanged
75% dose of all drugs
75% dose of all drugs
Unchanged
Interruption
75% dose of ifosfamide
75% dose of all drugs
75% dose of all drugs
75% dose of all drugs
75% dose of all drugs
3. Renal impairment
GFR ml/min
> 60
40-60
< 40
Ifosfamide Dose
Full dose
70% of dose
Clinical decision
Etoposide Dose
Full dose
80% of dose
Clinical decision
Carboplatin: Contraindicated if CrCl<20ml/min
3. Hepatic impairment
Etoposide
Bilirubin
micromol/L
26-51
>51
AST/ALT
IU/L
60-180
>180
Etoposide Dose
50%
omit
Ifosfamide
No standard dose modification therefore clinical decision. Consider dose
reduction of ifosfamide in patients with significant hepatic dysfunction. The
manufacturer states that ifosfamide is not recommended if bilirubin>17umol/l or
serum transaminases or ALP>2.5xULN. Clinical decision.
Carboplatin: No dose reduction necessary.
DATE OF ISSUE 06.03.17
REVIEWED BY K.GRAHAM
/ C.WARD
REVIEW DATE 06.03.19
VERSION 3
AUTHORISED BY: Dr J Addada
*** VALID ON DATE OF PRINTING ONLY ***
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DERBY-BURTON LOCAL CANCER NETWORK
FILENAME
R-ICE
HCCPG B55
CONTROLLED DOC NO:
CSIS Regimen Name:
R-ICE
4. Neurotoxicity
Ifosfamide may cause a reversible encephalopathy at high doses. This usually
manifests as decreased rousability and disorientation often leading to
somnolence. In severe cases this can progress to irreversible encephalopathy
and death. Patients should be monitored regularly for signs/symptoms of
neurotoxicity.
Symptoms may develop within 2 hours of initiation or up to 28 days after
treatment; the usual onset is within 24-96 hours after the initiation of ifosfamide
and disappears within 48-72 hours of discontinuing ifosfamide.
Risk factors include:
 Elevated serum creatinine
 Previous exposure to cisplatin (cumulative dose >300mg/m 2)
 Low serum albumin. Discuss with Consultant if albumin <35g/l.
 Previous exposure to ifosfamide
 Abdominal lymphoma
 Short ifosfamide infusions (<6hrs)
 Prior cranial irradiation
 Other CNS-active drugs
If a patient is at risk of developing encephalopathy, consideration should be
given to the use of an alternative (non-ifosfamide containing) regimen.
Management of ifosfamide-induced encephalopathy
1. Discontinue ifosfamide.
2. Consider use of methylthioninium chloride (methylene blue) (Unlicensed
indication):
50mg slow intravenous bolus over 5 minutes. This may need to repeated up
to 6 times/day.
Methylthioninium chloride is available as a 0.5% solution; 10ml of 0.5%
solution is equivalent to 50mg. The 0.5% solution does not require filtering,
and is incompatible with sodium chloride 0.9% so will need to be diluted in
5% dextrose if dilution is necessary.
3. In patients who have had a history of ifosfamide-induced encephalopathy and
require further doses of ifosfamide, methylthioninium chloride has been used
prophylactically (50mg slow intravenous bolus over 5 minutes 4 times daily).
DATE OF ISSUE 06.03.17
REVIEWED BY K.GRAHAM
/ C.WARD
REVIEW DATE 06.03.19
VERSION 3
AUTHORISED BY: Dr J Addada
*** VALID ON DATE OF PRINTING ONLY ***
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DERBY-BURTON LOCAL CANCER NETWORK
FILENAME
R-ICE
HCCPG B55
CONTROLLED DOC NO:
CSIS Regimen Name:
R-ICE
4. Haloperidol & lorazepam have been reported to help with hallucinations and
agitation. Use with caution, -no controlled trials exist and these agents may
mask the evolution or severity of neurotoxicity.
Methylthioninium chloride frequently colours secretions blue, patients should
be made aware of this effect
4. Haemorrhagic Cystitis
Urine should be dipstick tested for signs of haematuria.
If microscopic haematuria is present, an increase in hydration can be used to
facilitate the elimination of ifosfamide and its metabolites. Additional mesna
appears to have little benefit as its role is in prevention rather than treatment.
However, owing to its low toxicity consideration should be given to increasing the
dose of mesna (although arbitrary, local practice is to double the dose).
In the case of frank haematuria, a urological opinion should be sought. Mesna
is of little value at this point as it’s role is to prevent haemorrhagic cystitis and
not for its treatment.
Supportive care
1. Consider allopurinol (300mg) once a day if bulky disease. Reduce dose to
100mg daily if GFR <10mls/min.
2. All patients should receive Pneumocystis jiroveci prophylaxis throughout
treatment::
Co-trimoxazole 480mg ONCE daily. In cases of allergy to co-trimoxazole,
consider dapsone 100mg daily.
3. Aciclovir 400mg twice daily.
4. All patients receive primary prophylaxis with GCSF. GCSF is mandatory for stem
cell collection. Typically this is performed after the 2nd or 3rd MATRIX cycle or the
1st R-ICE cycle in selected patients with extensive or bulky disease.
References
1. Kewalramani et al. Rituximab and ICE as second line therapy before autologous
stem cell transplantation for relapsed or primary refractory diffuse large B cell
lymphoma. Blood 2004; 103:3684-3688.
2. IELSG 42 Protocol- version 3.0- Fenruary 08, 2016
DATE OF ISSUE 06.03.17
REVIEWED BY K.GRAHAM
/ C.WARD
REVIEW DATE 06.03.19
VERSION 3
AUTHORISED BY: Dr J Addada
*** VALID ON DATE OF PRINTING ONLY ***
PAGE 6 of 6