2.07 Protocol Name:
Indication


CHOP & Rituximab
Intermediate and high grade, B-cell non-Hodgkins
lymphoma expressing CD20.
Second or third line therapy for low grade, B cell nonHodgkins lymphoma expressing CD20.
Pre-treatment Evaluation

Document histological sub-type of lymphoproliferative
disorder according to WHO classification.

Document disease stage clinically, including presence or
absence of B symptoms. Investigations should include CT
scan of chest, abdomen and pelvis, bone marrow aspirate
& trephine biopsy.

Document FBC (with film), U&E, creatinine, LFTs, calcium,
glucose, immunoglobulin levels and a direct antiglobulin
test. LDH is also required for patients with aggressive NHL.

CSF cytology must be obtained for patients with aggressive
NHL involving peripheral blood, testis, orbit, paranasal
sinus or paraspinal area.

Document WHO performance status of patient.

For aggressive NHL, document International Prognostic
Index (IPI) score according to NEJM 1994; 329: 987-994

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.

Consider intravenous hydration in patients with bulk
disease and tumour lysis precautions according to local
practice.

If appropriate, discuss the possibility of pregnancy with
female patients of childbearing age and the need for
contraception with both male and female patients.

If appropriate, discuss potential risk of infertility with patient
and relatives.
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Drug Regimen
(OPCS code: X71.2)
Day
Drug
Dose
1
Rituximab
375mg/m²
1
1
1
1-5
Rou
te
IV
Comments
See below for infusion speed;
give before CHOP
Cyclophosphamide 750mg/m²
IV
Bolus or Infusion in 0.9% saline
over 30 mins.
Doxorubicin
50mg/m²
IV
Bolus via fast running drip of
0.9% saline.
Vincristine
1.4mg/m² †
IV
In 20mls 0.9% saline – bolus
(max 2mg)
injection as per national protocol.
Prednisolone
40mg/m²
PO
Take in the mornings; swallow
(max 100mg)
whole with food.
†
Consider Vincristine 1mg for elderly patients (>70 years)
Rituximab infusion speed:



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 day-care units have implemented
this locally as a safe and time efficient method of reducing
the infusion time of R-CHOP for patients.
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.
Cycle Frequency

Every 21 days.

Treat to CR or maximum response plus further two cycles
(maximum 8 cycles).
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Dose Modifications

Hepatic impairment:
Serum Bilirubin
Modification
<1.5 x upper limit of normal
100%
1.5-3.0 x upper limit of normal
50% doses of Doxorubicin
100% dose of other drugs
>3.0 x upper limit of normal
25% doses of Doxorubicin
100% dose of other drugs

Renal impairment:
Creatinine clearance (mls/min)
>50
10-50
<10



Modification
100%
75% dose of Cyclophosphamide
50% dose of Cyclophosphamide
Haematological:
No dose modification on the first cycle. If, at the start of
subsequent cycles, the neutrophil count is <1.0 x 109/l and
the platelets<50 x 109/l, therapy should be delayed for 1
week and then given with the following dose modifications
below:
However, patients with a good prognosis should be
administered GCSF in doses sufficient to allow full dose of
treatment on schedule. 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.
Neutrophils x 109/l
>1.0
<1.0
Dose Given
100%
Delay all drugs for 1 week
Platelets x 109/l
>75
50-74
Dose Given
100%
75% doses of Cyclophosphamide and
Doxorubicin.
100% doses of Vincristine and Prednisolone
Delay all drugs for 1 week.
<50


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Vincristine: If patient complains of significant constipation
or sensory loss in fingers and/or toes, discuss possible
dose reduction with Consultant before administration.
Doxorubicin: Maximum cumulative dose = 450mg/m2
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Previous neutropenic sepsis, discuss the use of
prophylactic antibiotics and/or G-CSF support with
Consultant.

-
Rituximab
Circulating tumour cells > 50 x 109/l consider delay of
Rituximab
Tumour bulk; single lesion >10cm consider delay of
Rituximab
Investigations prior to subsequent cycles



FBC.
LFT, U&E, Creatinine, LDH ESR, Glucose if indicated,
Immunoglobulins (after last cycle).
If clinical response, formal restaging should be undertaken
after 4 cycles and again after 6 cycles.
Concurrent Medication


Allopurinol 300mg OD PO (100mg if creatinine clearance
<20mls/min) for first 2 cycles.
Premedicate Rituximab using Paracetamol 1gm PO and
Chlorpheniramine 10mg IV; consider Corticosteroids e.g.
100mg Hydrocortisone
Anti-emetics
This regimen has moderate emetic potential - refer to local
protocol
References

Vose JM et al. Phase II study of Rituximab in combination
with CHOP chemotherapy in patients with previously
untreated, aggressive non-Hodgkin’s Lymphoma.
J Clin Oncol 2001;19(2):389-97.

Howard O et al. Rituximab/CHOP induction therapy in
newly diagnosed patients with mantle cell lymphoma.
Blood 1999;94,suppl1:2804a.

Coiffier B et al. CHOP chemotherapy plus Rituximab
compared with CHOP alone in elderly patients with diffuse
large-B-cell lymphoma.
N Engl J Med 2002;346:235-242.
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
Sehn L, Donaldson J, Filewich, Fitzgerald C, Gill K, Runzer
N, Searle B, Souliere S, Spinelli J, Sutherland J and
Connors J. Abstract #1407. ASH meeting Dec 2004
Patient Information
http://www.cancerbackup.org.uk/Treatments/Chemotherapy/Combinationregimen/RCHOP
Written by:
Dr George Hughes, Dr Ed Kanfer, Dr Donald Macdonald, Dr Mallika Sekhar,
Pauline McCalla and Melanie Schenck
Authorised by:
WLCN Haematology TWG
Date for review by Haematology TWG:
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