DERBY-BURTON LOCAL CANCER NETWORK FILENAME R-GCVP.DOC CONTROLLED DOC NO: HCCPG B12 CSIS Regimen Name: R-GCVP. R-GCVP Regimen

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1 R-GCVP 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 CD 20 positive Diffuse Large B Cell Lymphoma in patients unable to receive RCHOP due to inadequate cardiac function or borderline cardiac function with co-morbidities Treatment Intent Curative Anti-Emetics Pre-chemotherapy 2 Frequency & Duration Post-chemotherapy A Every 21 days for a maximum of 6 cycles After 2 cycles, responding patients may be considered for high dose chemotherapy and autologous stem cell transplant Day 1 Ondansetron 8mg As a single oral dose Paracetamol 1g As a single oral dose 30 minutes prior to rituximab Chlorphenamine 10mg As a single intravenous bolus 30 minutes prior to rituximab Hydrocortisone 100mg As a single intravenous bolus 30 minutes prior to rituximab Prednisolone 100mg Oral once daily for 5 days - give first dose 30 minutes prior to rituximab Gemcitabine Cycle 1 750mg/m 2 Cycle 2 875mg/m 2 Cycle 3 onwards 1000mg/m 2 (see notes below) Intravenous infusion in 250ml sodium chloride 0.9% over 30 minutes Cyclophosphamide 750mg/m 2 Intravenous bolus Vincristine 1.4mg/m 2 maximum 2mg (1mg if >70 yrssee notes) Intravenous infusion in 50ml sodium chloride 0.9% over 5-10 minutes Rituximab 375mg/m 2 Intravenous infusion in 500ml REVIEWED BY K Graham AUTHORISED BY: Dr J Addada PAGE 1 of 6

2 sodium chloride 0.9% Metoclopramide 10mg Oral four times daily for 2 days then as required Allopurinol 300mg Oral once daily for 1 or 2 cycles Omeprazole 20mg Oral once daily for 5 days Cotrimoxazole 480mg Oral once daily for 21 days Aciclovir 400mg Oral twice daily for 21 days Day 8 Ondansetron 8mg As a single oral dose Dexamethasone 8mg As a single oral dose Gemcitabine Cycle 1 750mg/m 2 Cycle 2 875mg/m 2 Cycle 3 onwards 1000mg/m 2 (see notes below) Intravenous infusion in 250ml sodium chloride 0.9% over 30 minutes Day 9 Filgrastim biosimilar 300micrograms Subcutaneous injection ONCE daily on Days 9, 11, 13, 15 Notes: Rituximab This section should be read in conjunction with the Guidelines for the administration of Rituximab. 1. The day 1 dose of prednisolone should be given 30 mins prior to receiving rituximab. Premedication consisting of analgesia and an antihistamine and an intravenous corticosteroid should always be administered 30 minutes before each infusion of rituximab. (e.g. paracetamol 1g oral STAT and chlorphenamine 4mg oral or 10mg IV bolus STAT and hydrocortisone 100mg IV STAT). In addition pethidine 25mg IV should be available in case of a severe infusion reaction. 2. Rituximab doses should be rounded to the nearest 100mg. Use rituximab rate calculator to assist with rate escalation of rituximab infusion. 3. Occurrence of an Infusion Related Event or Hypersensitivity: Stop the infusion and contact a doctor. When symptoms improve, continue the infusion at half the rate prior to the reaction. REVIEWED BY K Graham AUTHORISED BY: Dr J Addada PAGE 2 of 6

3 Accelerate the infusion rate more slowly as tolerated by the patient. Pre-treatment tests Day 1: FBC, U&Es, LFTs Day 8: FBC Dose modifications and toxicities Patients older than 70 or those with poor performance status: Reduce vincristine dose to a fixed dose of 1mg. 1. Gemcitabine dose The dose of Gemcitabine may be escalated sequentially if tolerated with no evidence of haematological toxicity from 750mg/m 2 in cycle 1 to 875mg/m 2 in cycle 2 and 1000mg/m 2 in cycle 3 to continue thereafter. 2. Haematological toxicity At the start of each cycle the neutrophil count should be 1.0 x 10 9 /l and platelets 75 x 10 9 /l. Prior to every cycle i.e. Day 1 Neutrophils Platelets GCVP dose adjustment 1.0 x 10 9 /L & 75 x 10 9 /L 100% dose x 10 9 /L or x 10 9 /L 75 % dose of Gemcitabine, cyclophosphamide and Vincristine < 0.5 x 10 9 /L or < 50 x 10 9 /L Delay until neutrophils 1.0 x 10 9 /L and platelets 75 x 10 9 /L and give 100% dose. Prior to Day 8 gemcitabine: Neutrophils Platelets Day 8 Gemcitabine dose adjustment 1.0 x 10 9 /L & 75 x 10 9 /L 100% dose x 10 9 /L or x 10 9 /L 75 % dose < 0.5 x 10 9 /L or < 50 x 10 9 /L Omit Consider increasing the duration of filgrastim in the event of neutropaenic sepsis or delays to treatment due to neutropaenia. If recurrent neutropaenic sepsis or delays to treatment then reduce to 75% dose of Gemcitabine, Cyclophosphamide and Vincristine. REVIEWED BY K Graham AUTHORISED BY: Dr J Addada PAGE 3 of 6

4 2. Renal impairment Cyclophosphamide GFR ml/min Dose >20 100% % <10 50% Gemcitabine GFR ml/min Dose >30 100% <30 Consider dose reductionclinical decision Dose reduction for renal impairment is not required for vincristine. 3. Hepatic impairment Consider maintaining doses if liver impairment is due to lymphoma Vincristine Bilirubin AST/ALT micromol/l Units/l Dose or % >51 & normal 50% >51 & >180 omit Gemcitabine Bilirubin Dose micromol/l % >27 80% of dose initially and increase if tolerated. No reductions required for Cyclophosphamide REVIEWED BY K Graham AUTHORISED BY: Dr J Addada PAGE 4 of 6

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 Neutrophils <0.5 x 10 9 /l Platelets <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 Permanent sensory loss that interferes with function 5. Non-haematological toxicities With-hold treatment for any Grade 3 or 4 non-haematological toxicities, excluding neuropathy. Once the symptoms of the toxicity have resolved, treatment may be re-initiated at a 25% reduced dose. Gemcitabine commonly causes skin rashes. Treat with oral antihistamines and topical corticosteroids if needed. Gemcitabine commonly causes elevations in liver enzymes (ALT/AST and ALP) in up to 60% of patients. Elevations are usually transient and reversible. 6. Drug Interactions Itraconazole, posaconazole and voriconazole inhibit the metabolism of vincristine increasing neurotoxicity, therefore are contraindicated. REVIEWED BY K Graham AUTHORISED BY: Dr J Addada PAGE 5 of 6

6 7. Alcohol content of gemcitabine Doses of gemcitabine not available as ready- made infusions contain up to approximately 11g of ethanol (1.5units). Patients should be advised not to drive on the day of treatment. Where alcohol content is a concern please contact pharmacy for advice about alternative formulations. Supportive care 1. Allopurinol 300mg once daily for the first 1 or 2 courses of therapy whilst there is bulky disease. Reduce dose to 100mg if GFR < 10ml/min. 2. All patients should receive Pneumocystis jirovecii prophylaxis throughout treatment: Co-trimoxazole 480mg ONCE daily. In cases of allergy to co-trimoxazole, consider dapsone 100mg daily. 3. Aciclovir 400mg bd. 4. Omeprazole 20mg once daily for 5 days (i.e. concurrently with prednisolone) 5. All patients receive primary prophylaxis with GCSF (filgrastim). References 1. Fields A et al. De Novo Treatment of Diffuse Large B-Cell Lymphoma With Rituximab, Cyclophosphamide, Vincristine, Gemcitabine and Prednisolone in Patients With Cardiac Comorbidity: A United Kingdom National Cancer Research Institute Trial. J Clin Oncol 2014; 32(4): Using Vinca Alkaloid Minibags (Adults/Adolescent Units); NPSA Rapid Response Alert 4; 11 August SPC Gemcitabine accessed online on 6/6/14 at 4. Field K, Dow C and Michael M. Part I: Liver function in oncology: biochemistry and beyond. Lancet Oncol 2008;9: SPC Vincristine accessed online on 6/6/14 at REVIEWED BY K Graham AUTHORISED BY: Dr J Addada PAGE 6 of 6