Regimen R-CEOP Therapeutic Intent

1 Page 1 of 3 Regimen R-CEOP Indication diffuse large B Cell lymphoma with contraindications to anthracyclines Therapeutic Intent Radical/Curative Day Medication Dose Route Administration Details 1 Rituximab 375mg/m2 IV Add to sodium chloride See local protocol or product SPC for information of rate of infusion 1 Vincristine IV Max dose 2mg. 50ml sodium chloride minibag over 5-10 minutes. 1 Etoposide 50mg/m2 IV 500ml to 1000ml sodium chloride over 1-2 hours 1 Cyclophosphamide 750mg/m2 IV Slow IV bolus injection or add to sodium chloride and give over 30 minutes. 2 and 3 Etoposide 100mg/m2 PO Take on an empty stomach. Round dose to the nearest 50mg. 1 to 5 Prednisolone 100mg or PO As a single dose with food in the morning. Day 1 may be given prior to the Rituximab infusion as part of the pre-med Cycle Frequency Every 21 days for 3-6 cycles depending on stage of disease Tests required prior to initiation of course FBC, U&E, LFT, Bone profile, glucose, LDH, B2M, serum Igs, hep B screen, electrophoresis.

2 Undertake relevant staging. Consider cardiac function tests. WHO performance status. Tests required prior to individual cycle FBC, U&E, LFT. Concurrent Medication Antihistamine, corticosteroid and paracetamol pre-medication prior to rituximab as per local policy. Allopurinol for at least the first cycle. Anti-emetics as per local policy. PPI. Consider antifungal, antiviral, PCP prophylaxis and mouthwashes as per local policy. Page 2 of 3 Dose Modifications Hepatic There is conflicting information regarding dose reduction of etoposide in hepatic impairment. Although etoposide is contraindicated in patients with severe hepatic dysfunction, the following advice is suggested by some reference sources. Serum Bilirubin (micromol/L) OR AST (units/L) Modification <26 <60 100% dose etoposide 26-51 60-180 50% dose etoposide >51 >180 Clinical Decision 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 >50 100% of etoposide 15-50 75% of etoposide <15 50% of etoposide Haematological No dose modifications for first cycle Neutrophils (x109/L) Modification < on day treatment due Delay cycle one or two weeks.

3 If count has not recovered after 14 days, stop chemotherapy Grade 4 neutropenia or any febrile neutropenia following any cycle of chemotherapy All subsequent cycles given with G-CSF support Grade 4 neutropenia leading to infection despite G-CSF support Reduce dose of cyclophosphamide and etoposide by 50% for all subsequent cycles Grade 4 neutropenia recurs despite 50% dose reduction in cyclophosphamide and etoposide Stop chemotherapy Platelets (x109/L) Modification Platelets <100 on day treatment due Delay cycle one or two weeks. If count has not recovered after 14 days chemotherapy will be stopped Grade 3 or 4 thrombocytopenia following any cycle of CHOP Reduce dose of cyclophosphamide and etoposide by 50% for all subsequent cycles Grade 3 or 4 thrombocytopenia recurs despite 50% dose reduction in cyclophosphamide and etoposide Stop chemotherapy Neurotoxicity Grade 2 motor weakness or Grade 3 sensory toxicity Give 50% vincristine Higher grades of neurological toxicity OMIT vincristine Page 3 of 3 Additional Information None.

4 References 1. 408 R-CHOP with Etoposide Substituted for Doxorubicin ( R-CEOP ): Excellent Outcome in diffuse large B Cell lymphoma for Patients with a Contraindication to Anthracyclines. Oral and Poster Abstracts Oral Session: lymphoma : Chemotherapy, excluding Pre-Clinical Models - Non-Hodgkin lymphoma : Therapy. Monday, December 7, 2009: 11:45 AM 2. Dose Adjustments for Cytotoxics in Hepatic Impairment January 2009, available at 3. Dose Adjustments for Cytotoxics in Renal Impairment January 2009, available at 4. SPC for rituximab available at Author Pharmacy CNG Approved & Checked by Haematology CNG (Review Date = Jan 2017)