2.07 Protocol Name: CHOP & Rituximab

Transcription

1 2.07 Protocol Name: CHOP & Rituximab Indication Intermediate and high grade, B-cell non-hodgkins lymphoma expressing CD20. Second or third line therapy for low grade, B cell non- Hodgkins 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: 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 R-CHOP Version 2 0 Jul08.doc Page 1 of 5

2 Drug Regimen (OPCS code: X71.2) Day Drug Dose Rou Comments te 1 Rituximab 375mg/m² IV See below for infusion speed; give before CHOP 1 Cyclophosphamide 750mg/m² IV Bolus or Infusion in 0.9% saline over 30 mins. 1 Doxorubicin 50mg/m² IV Bolus via fast running drip of 0.9% saline. 1 Vincristine 1.4mg/m² (max 2mg) IV In 20mls 0.9% saline bolus injection as per national protocol. 1-5 Prednisolone 40mg/m² (max 100mg) PO Take in the mornings; swallow 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) R-CHOP Version 2 0 Jul08.doc Page 2 of 5

3 Dose Modifications Hepatic impairment: Serum Bilirubin Modification <1.5 x upper limit of normal 100% 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) Modification >50 100% % dose of Cyclophosphamide <10 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 Dose Given > % <1.0 Delay all drugs for 1 week Platelets x 109/l Dose Given >75 100% % doses of Cyclophosphamide and Doxorubicin. 100% doses of Vincristine and Prednisolone <50 Delay all drugs for 1 week. 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/m R-CHOP Version 2 0 Jul08.doc Page 3 of 5

4 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): 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: R-CHOP Version 2 0 Jul08.doc Page 4 of 5

5 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 CHOP 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: 2 07 R-CHOP Version 2 0 Jul08.doc Page 5 of 5