High Dose Cytarabine plus high dose Methotrexate for CNS Lymphoma

Transcription

1 High Dose Cytarabine plus high dose Methotrexate for CNS Lymphoma 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 Primary or Secondary CNS lymphoma Treatment Intent Radical Anti-Emetics Pre-chemotherapy 3 Post-chemotherapy C Frequency and duration Every 21 days for 4 cycles. Followed by complementary whole-brain radiotherapy within 4 weeks from the last course of chemotherapy as appropriate Day 1 Day 2 Ondansetron 8mg Oral Dexamethasone 8mg Oral (provided urine ph >7.5) Methotrexate 500mg/m 2 Intravenous in 100ml sodium chloride 0.9% over 15 mins, immediately followed by Methotrexate 3000mg/m 2 Intravenous in 0.9% over 3 hours concurrently with REVIEWED BY K. GRAHAM AUTHORISED BY: Dr J Addada PAGE 1 of 6 Intravenous (combined rate with = 125ml/m 2 /hr) Metoclopramide 10mg Oral four times daily for 4 days then as required

2 Followed by REVIEWED BY K. GRAHAM AUTHORISED BY: Dr J Addada PAGE 2 of 6 Day 3 Dexamethasone 8mg Oral Ondansetron 8mg Oral TWICE daily for 2 days then as needed Cytarabine 2000mg/m 2 Intravenous in 0.9% over 1 hour at 8am 24 hours after 30 hours after 36 hours after 42 hours after 48 hours after Cytarabine 2000mg/m 2 Intravenous in 0.9% over 1 hour at 8pm (i.e. 12 hours between doses) Prednisolone (Predsol 1 drop Into both eyes 4 times 0.5%) or Dexamethasone daily for 7 days 0.1% eye drops

3 Day 4 Dexamethasone 8mg Oral Cytarabine 2000mg/m 2 Intravenous in 0.9% over 1 hour at 8am Cytarabine 2000mg/m 2 Intravenous in 0.9% over 1 hour at 8pm (i.e. 12 hours between doses) Dexamethasone 4mg Oral TWICE daily at 8am and 6pm for 2 days, then Dexamethasone 2mg Oral TWICE daily at 8am and 6pm for 2 days 54 hours after 60 hours after 66 hours after 72 hours after Day 5 78 hours after REVIEWED BY K. GRAHAM AUTHORISED BY: Dr J Addada PAGE 3 of 6

4 84 hours after 90 hours after 96 hours after Day 9 Filgrastim biosimilar 300 micrograms Subcutaneous injection ONCE DAILY for 7 days Notes: Supportive care 1. Consider allopurinol (300mg) once a day for the prevention of tumour lysis syndrome. Reduce dose to 100mg daily if GFR <30ml/min. 2. All patients should receive Pneumocystis jirovecii prophylaxis throughout treatment as dapsone 100mg daily. (Note that cotrimoxazole should not be given due to the potential for interaction with ). 3. Aciclovir 400mg twice daily. 4. Hydration (with sodium bicarbonate containing s) throughout treatment is essential (at least 3 litres a day). Urinary ph must be maintained between 7 and 8 throughout the period of treatment to ensure excretion. If 100mmol sodium bicarbonate / litre is insufficient to keep the urine ph>7, give mmol sodium bicarbonate (i.e ml of 8.4% sodium bicarbonate) over minutes (piggy back onto existing hydration fluids). If repeated extra doses are required, increase the hydration fluids to contain 150mmol sodium bicarbonate / litre. 5. Patients require a double or triple lumen central venous catheter 6. Strict fluid balance chart should be maintained. Prescribe furosemide 20-40mg stat if fluid balance is 2 litres positive. 7. Methotrexate levels every 24 hours, at 48 hours after commencement of the. If the patient is not vomiting folinic acid may be given orally after the first two doses. Folinic acid rescue should continue until the serum level falls to less than 0.1 micromol/l REVIEWED BY K. GRAHAM AUTHORISED BY: Dr J Addada PAGE 4 of 6

5 Drug interactions AVOID concurrent use of the following drugs: Aspirin Non-steroidal anti-inflammatories Penicillins (Including Tazocin ) Aminoglycosides Trimethoprim (including co-trimoxazole) Probenacid Sulphonamides Neutropenic sepsis should be managed with meropenem (discuss with Microbiologist) Pre-treatment tests Prior to day 1: FBC, U&Es, LFTs. Prior to cycle 1 and cycle 3: Creatinine clearance measured by 24 hour urine collection or chromium EDTA. Repeat on cycle 2 if there is delayed excretion with the 1 st cycle. Repeat if there is a 20% or greater increase in serum creatinine from the previous cycle. Consider baseline echocardiogram (patients need to be able to tolerate large volumes of fluid). Dose modifications and toxicities 1. Haematological Neutrophils 1x10 9 /l and platelets 100x10 9 /l prior to each cycle. 2. Renal impairment GFR ml/min Methotrexate dose > 80 Full dose % dose <50 Do not give Consider alternative approaches (e.g. intrathecal) GFR ml/min Cytarabine dose >60 100% % % <30 contraindicated REVIEWED BY K. GRAHAM AUTHORISED BY: Dr J Addada PAGE 5 of 6

6 Check serum creatinine levels daily whilst receiving folinic acid rescue. 3. Hepatic impairment Methotrexate Bilirubin AST/ALT micromol/l Units/L Dose <50 & < % or >180 75% >85 omit Cytarabine: If blirubin >34 micromol/l give 50% dose cytarabine. 4. Table for the calculation of folinic acid rescue on the basis of MTX plasma levels. Time after Methotrexate Plasma Concentration (micromol/l) < > hours None 15mg/m 2 6hrly 15mg/m 2 6hrly 10mg/ m 2 72 hours None 15mg/m 2 6hrly 10mg/ m 2 100mg/ m 2 96 hours None 15mg/m 2 6hrly 10mg/ m 2 100mg/ m hours None 15mg/m 2 6hrly 10mg/ m 2 100mg/ m 2 100mg/ m mg/ m mg/ m mg/ m 2 The dose of folinic acid should also be increased if serum creatinine increases >50% from baseline. References: 1. Ferreri A.J.M et al. High dose cytarabine plus high dose versus high dose alone in patients with primary CNS lymphoma: a randomised phase 2 trial. Lancet 2009; 374: UKALL XII trial protocol V4.1 Feb Communication with Haematology team University Hospitals of Leicester 4. The North London Cancer Network; Dosage Adjustment for Cytotoxics in Renal and Liver Impairment 2009 REVIEWED BY K. GRAHAM AUTHORISED BY: Dr J Addada PAGE 6 of 6