CEOP Regimen Available for Routine Use in Burton in-patient Derby in-patient Burton day-case Derby day-case Burton community Derby community Burton out-patient Derby out-patient Indication T-cell non-hodgkin s lymphoma Diffuse large B-cell lymphoma. Patients with a contraindication to anthracyclines e.g inadequate cardiac function, prior exposure to anthracyclines, multiple comorbidities. Treatment Intent Radical Anti-Emetics Pre-chemotherapy 2 Frequency & Duration Post-chemotherapy A Every 21 days for 3-6 cycles. Restage after 4 cycles Day 1 Ondansetron 8mg Oral as a SINGLE dose prior to chemotherapy Prednisolone 100mg Oral once daily for 5 days. First dose given prior to chemotherapy Cyclophosphamide 750mg/m 2 Intravenous bolus Etoposide 50mg/m 2 Intravenous infusion in 500ml 0.9% sodium chloride PVC-free bag over 60 mins. Maximum concentration 0.4mg/ml Vincristine 1.4mg/m 2 maximum 2mg Intravenous infusion in 50ml sodium chloride 0.9% over 5-10 minutes (See notes) Metoclopramide 10mg Oral four times daily for 2 days and then as required Allopurinol 300mg Oral once daily for 1-2 cycles Cotrimoxazole 480mg Oral once daily for 21 days Omeprazole 20mg Oral once daily for 5 days Aciclovir 400mg Oral twice daily for 21 days Day 2 Etoposide 100mg/m 2 ORALLY once daily for 2 days Round to the nearest 50mg. Notes: REVIEWED BY K.Graham AUTHORISED BY: Dr J Addada PAGE 1 of 5
Pre-treatment investigations FBC, U&Es and LFTs pre each cycle. Supportive care 1. It is advisable to give allopurinol (300mg) once a day for the first 1 or 2 courses of therapy whilst there is bulky disease. Reduce dose to 100mg daily if GFR <10mls/min. 2. All patients should receive Pneumocystis jirovecii and antiviral prophylaxis throughout treatment: Co-trimoxazole 480mg ONCE daily. In cases of allergy to co-trimoxazole, consider dapsone 100mg daily. Aciclovir 400mg twice daily. 3. Omeprazole 20mg ONCE daily for 5 days (i.e. concurrently with prednisolone). 4. GCSF 300 micrograms ONCE daily by subcutaneous injection on days 7, 9, 11 (& 13 if) 65 years or has developed neutropenic sepsis with previous cycles of chemotherapy. Dose modifications and toxicities Patients older than 70: Consider reducing the initial vincristine dose to a fixed dose of 1mg ( elderly CHOP ) Consider giving a 1 week steroid pre-phase. Consider an initial dose reduction. Doses may be escalated up in subsequent cycles depending on tolerability. 1. Haematological toxicity At the start of each cycle the neutrophil count should be > 1.0 x 10 9 /l and platelets > 100 x 10 9 /l. a) Neutropenia Neutrophils <1.0 x 10 9 /l Grade 4 neutropenia* or febrile neutropenia following any cycle of CHOP Grade 4 neutropenia* leading to infection despite GCSF support Grade 4 neutropenia* recurs despite 50% dose reduction in cyclophosphamide and etoposide Delay one week and give GCSF with subsequent cycles (days 7,9,11 initially) Give GCSF support with all subsequent cycles Consider 50% reduction of cyclophosphamide and etoposide for all subsequent cycles Consider termination of protocol REVIEWED BY K.Graham AUTHORISED BY: Dr J Addada PAGE 2 of 5
b)thrombocytopenia Platelets < 100 x 10 9 /l Grade 3 or 4 thrombocytopenia* following any cycle of CHOP Grade 4 thrombocytopenia* recurs despite 50% dose reduction in cyclophosphamide and etoposide Delay one week Reduce dose of cyclophosphamide and etoposide by 50% for all subsequent cycles Consider termination of protocol 2. Renal impairment Cyclophosphamide GFR ml/min Dose >20 100% 10-20 75% <10 50% Etoposide GFR ml/min Dose >50 100% 15-50 75% <15 50% Dose reduction for renal impairment is not required for doxorubicin or vincristine. 3. Hepatic impairment If liver impairment is due to lymphoma consider maintaining doses. Etoposide Bilirubin AST/ALT micromol/l Units/l Dose 26-51 or 60-180 50% >51 or >180 Clinical decision Vincristine Bilirubin AST/ALT micromol/l Units/L Dose 26-51 or 60-180 50% >51 & normal 50% >51 & >180 omit REVIEWED BY K.Graham AUTHORISED BY: Dr J Addada PAGE 3 of 5
4. Neurotoxicity Vincristine If grade 2 motor weakness* or grade 3 sensory toxicity*, reduce dose to 1mg or replace vincristine by vinblastine 6mg/m 2. For higher grade toxicity omit. *NCI Common Toxicity Criteria Grade Toxicity 1 2 3 4 Neutrophils 1.5-1.99 1.0-1.49 0.5-0.99 <0.5 x 10 9 /l Platelets 75-149 50-74 10-49 <10 x 10 9 /l Neuropathy (motor) Subjective weakness but no objective findings Mild objective weakness function, but not interfering with activities Objective weakness activities of daily living Paralysis Neuropathy (sensory) Loss of deep tendon reflexes or parasthesia (including tingling) but not function of daily living Objective sensory loss or parasthesia (including tingling) function, but not interfering with activities of daily living Sensory loss or parasthesia activities of daily living REVIEWED BY K.Graham AUTHORISED BY: Dr J Addada PAGE 4 of 5 Permanent sensory loss that interferes with function References 1. Bezwoda W, Ristogi RB, Erazo Valla A, et al. Long-term results of a multicentre randomised, comparative phase III trial of CHOP versus CNOP regimens in patients with intermediate- and high-grade non-hodgkin's lymphomas. Novantrone International Study Group. Eur J Cancer. 1995;31A:903-911 2. British Committee for Standards in Haematology - Guidelines on diagnosis and therapy Nodal non-hodgkin's lymphoma; August 2002 [draft 2] 3. Using Vinca Alkaloid Minibags (Adults/Adolescent Units); NPSA Rapid Response Alert 4; 11 August 2008 4. 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
5. How I treat patients with diffuse large B-cell lymphoma. James O. Armitage. Blood 2007; 110: 29-36 REVIEWED BY K.Graham AUTHORISED BY: Dr J Addada PAGE 5 of 5