Regimen R-CODOX M

Indication Burkitt’s Lymphoma or DLBCL with adverse features

Therapeutic Intent Radical/Curative

PATIENTS WITH GOOD PERFORMANCE STATUS

Day Medication Dose Route Administration Details
Slow IV bolus injection or add to sodium
1 Cyclophosphamide 800mg/m2 IV
chloride 0.9% and give over 30 minutes.
Refer to local intrathecal policy for further
2 and 4 Cytarabine 70mg Intrathecal
guidance.
1 Doxorubicin 40mg/m2 IV Slow IV Bolus injection
Add to sodium chloride 0.9%, see local
1 and 11 Rituximab 375mg/m2 IV protocol or product SPC for information on
rate of infusion.
Max dose 2mg. 50ml sodium chloride
1 and 8 Vincristine 1.5mg/m2 IV
0.9% minibag over 5-10 minutes.
Slow IV bolus injection or add to sodium
2 to 5 Cyclophosphamide 200mg/m2 IV
chloride 0.9% and give over 30 minutes.
Infuse over 60 minutes in 100ml or 250ml
10 Methotrexate 300mg/ m2 IV
sodium chloride 0.9%
Infuse over 23 hours in 1000ml sodium
10 Methotrexate 2700mg/ m2 IV
chloride 0.9%
13 G-CSF daily SC 7 day course.
Bolus injection. Refer to local intrathecal
15 Methotrexate 12.5mg Intrathecal
policy for further guidance.

An intensified intrathecal treatment is required for patients with CNS disease at diagnosis. This is given for
the first cycle of RCODOX M as follows;
Cycle Day Medication Dose Route Administration Details
R-CODOX-M 6 Cytarabine 70mg Intrathecal Refer to local intrathecal
R-CODOX-M 17 Methotrexate 12.5mg Intrathecal policy for further guidance.

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 PATIENTS WITH POORER PERFORMANCE STATUS
Day Medication Dose Route Administration Details
Slow IV bolus injection or add to sodium
1 Cyclophosphamide 800mg/m2 IV
chloride 0.9% and give over 30 minutes.
Refer to local intrathecal policy for further
2 and 4 Cytarabine 70mg Intrathecal
guidance.
1 Doxorubicin 40mg/m2 IV Slow IV Bolus injection
Add to sodium chloride 0.9%, see local
1 and 11 Rituximab 375mg/m2 IV protocol or product SPC for information on
rate of infusion.
Max dose 2mg. 50ml sodium chloride
1 and 8 Vincristine 1.5mg/m2 IV
0.9% minibag over 5-10 minutes.
Slow IV bolus injection or add to sodium
2 to 5 Cyclophosphamide 200mg/m2 IV
chloride 0.9% and give over 30 minutes.
Infuse over 60 minutes in 100ml or 250ml
10 Methotrexate 100mg/ m2 IV
sodium chloride 0.9%
Infuse over 23 hours in 1000ml sodium
10 Methotrexate 900mg/ m2 IV
chloride 0.9%
13 G-CSF daily SC 7 day course.
Refer to local intrathecal policy for further
15 Methotrexate 12.5mg Intrathecal
guidance.

An intensified intrathecal treatment is required for patients with CNS disease at diagnosis. This is given for
the first cycle of RCODOX M as follows;
Cycle Day Medication Dose Route Administration Details
R-CODOX-M 6 Cytarabine 70mg Intrathecal Refer to local intrathecal
R-CODOX-M 17 Methotrexate 12.5mg Intrathecal policy for further guidance.

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 Low risk patients – Give three cycles of RCODOX M only , each cycle
starting as soon as possible after neutrophils have regenerated >1 x109/L
and unsupported platelets >75 >1 x109/L.

High risk patients – Give 2 cycles alternating with 2 cycles of R-IVAC (i.e.
RCODOX M - R-IVAC - R-CODOX M - R-IVAC), each cycle starting as soon as
Cycle Frequency possible after neutrophils have regenerated >1 x109/L and unsupported
platelets >75 >1 x109/L. Two further doses of Rituximab will be
administered on Day 21 and 42 after day one of the final course of R-IVAC
to bring the total of Rituximab infusions to 8. The neutrophil count should
be > 1.0 x 109/l on the day of administration.

See treatment algorithm for further information on risk stratification.

FBC, U&E, LFT, Bone profile, glucose, LDH, serum Igs, electrophoresis.
GFR calculated using the wright equation or EDTA testing.
Tests required prior to Undertake relevant staging.
initiation of course Consider cardiac function tests.
WHO performance status.
Tumour Lysis screen.
Tests required prior to FBC, U&E, LFT.
individual cycle GFR calculated using the Wright equation or EDTA testing.
Antihistamine and paracetamol pre-medication prior to rituximab as per
local policy.
High risk of tumour lysis syndrome – strongly consider rasburicase.
Allopurinol for first two cycles.
Anti-emetics as per local policy.
Concurrent Medication PPI, although there have been case reports of reduced methotrexate
clearance in patients taking concomitant PPI. If patient is considered low
risk of GI disturbance ranitidine may be sufficient.
Consider antifungal, antiviral, PCP prophylaxis and mouthwashes as per
local policy (note interaction between co-trimoxazole and methotrexate
and between itraconazole and vincristine).
Stop methotrexate infusion at hour 24 regardless of dose given. Adequate
hydration is essential during high dose methotrexate.
Pre-hydration
For at least 6 hours prior to commencement of the methotrexate.
Hydration fluid – given pre, during and after MTX infusion;
• 1 litre Sodium Chloride 0.9% with 20mmol Potassium Chloride
add 50mmol Sodium Bicarbonate (= 50ml of 8.4% solution)
Hydration ALTERNATE WITH
• 1 litre Dextrose 5% with 20mmol Potassium Chloride
add 50mmol Sodium Bicarbonate (= 50ml of 8.4% solution)
Infusion rate
125ml/m2/hr (max. 250ml/hr).
Fluid balance
Check fluid balance at regular intervals (4-hourly) throughout each day,
taking early action if fluid overload occurs by giving furosemide if the urine

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 output falls below 400ml/m2 in any given 4-hour period.
Check urine pH
Adjust the sodium bicarbonate concentration to maintain the urinary pH
between 7 and 8 (i.e. alkaline). A urinary pH greater than 7 must be
achieved before starting the methotrexate infusion.
Serum methotrexate levels should be obtained as follows;
• Initially 48 hours after commencement of methotrexate
• Then daily until methotrexate level is below 5 x 10-8 M (or
0.05µmol/L) when rescue is stopped
Commence folinic acid rescue at hour 36 from start of methotrexate
Folinic acid rescue &
infusion.
Methotrexate levels
Administer intravenously at a dose of 15mg/m2 every 3 hours from hours
36 to 48 and then continue folinic acid every 6 hours until serum
methotrexate level < 5 x 10-8 M (or 0.05µmol/L).
Folinic acid can be given orally after the first 24 hours if patients are
compliant, not vomiting and otherwise without complication.

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Dose Modifications
Hepatic Serum Bilirubin AST/ ALT Modification
(micromol/L) (units)

If AST 2-3 x ULN 75% of doxorubicin dose

21-50 Or If AST >3x ULN 50% of doxorubicin dose
51-85 25% of doxorubicin dose
>85 Omit doxorubicin
26-51 Or 60-180 50% of vincristine dose
>51 And Normal 50% of vincristine dose
>51 And >180 Omit
Renal Creatinine clearance (ml/min) Modification
>20 100% of cyclophosphamide
10-20 75% of cyclophosphamide
<10 50% of cyclophosphamide
>80 100% of methotrexate
50-80 50% of methotrexate
A creatinine clearance of at least
50ml/min is required to proceed
<50 with this regimen, consider
alternative treatment if poor renal
function
Haematological
There are no dose modifications for haematological toxicity. Treatment should be
delayed until neutrophil count >1 x109/L and unsupported platelets >75 x109/L
Neurotoxicity Grade 2 motor weakness or Grade 3 sensory Give 50% vincristine
toxicity
Higher grades of neurological toxicity OMIT vincristine

Additional Information None.

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 Mead GM et al. A prospective clinicopathological study of dose
modified CODOX-M/IVAC in patients with sporadic Burkitt lymphoma
defined using cytogenetic and immunophenotypic criteria (MRC/NCRI
LY10 trial). Blood (2008)112:2248-2260
References Dose Adjustments for Cytotoxics in Hepatic Impairment January 2009,
available at www.eastmidlandscancernetwork.nhs.uk
Dose Adjustments for Cytotoxics in Renal Impairment January 2009,
available at www.eastmidlandscancernetwork.nhs.uk
www.medicines.org.uk

Author Pharmacy CNG

Approved & Checked by Haematology CNG (Review Date = Jan 2017)

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