DERBY-BURTON LOCAL CANCER NETWORK FILENAME R-CODOX-M.DOC CONTROLLED DOC NO: HCCPG B115 CSIS Regimen Name: R-CODOXM. Rituximab + CODOX-M

Transcription

1 Rituximab + CODOX-M 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 Burkitt s and Burkitt-like non-hodgkin s Lymphoma Treatment Intent Anti-Emetics Pre-chemotherapy 3 Post-chemotherapy A Frequency & Duration See notes below Day 0 Cytarabine 70mg Intrathecal injection Day 1 Prednisolone 100mg Oral 30 minutes prior to rituximab Chlorphenamine 10mg Intravenous bolus 30 minutes prior to rituximab Hydrocortisone 100mg Intravenous bolus 30 minutes prior to rituximab Paracetamol 1g Oral 30 minutes prior to rituximab Rituximab 375mg/m 2 Intravenous infusion in 500ml sodium chloride 0.9% Ondansetron 8mg Oral or intravenous pre-chemotherapy Cyclophosphamide 800mg/m 2 Intravenous infusion in 250ml sodium Vincristine 1.5mg/m 2 (Maximum 2mg) Intravenous infusion in 50ml sodium chloride 0.9% over 5-10 minutes Doxorubicin 40mg/m 2 Intravenous bolus Dapsone 100mg Oral once daily until lymphocytes >1.0 x 10 9 /l Aciclovir 400mg Oral twice daily until lymphocytes >1.0 x 10 9 /l AUTHORISED BY Dr J Addada PAGE 1 of 8

2 Metoclopramide 10mg Oral four times daily for 8 days as required Day 2 Ondansetron 8mg Oral or intravenous pre-chemotherapy Cyclophosphamide 200mg/m 2 Intravenous infusion in 250ml sodium Day 3 Ondansetron 8mg Oral or intravenous pre-chemotherapy Cyclophosphamide 200mg/m 2 Intravenous infusion in 250ml sodium Cytarabine 70mg Intrathecal injection Day 4 Ondansetron 8mg Oral or intravenous pre-chemotherapy Cyclophosphamide 200mg/m 2 Intravenous infusion in 250ml sodium Day 5 Ondansetron 8mg Oral or intravenous pre-chemotherapy Cyclophosphamide 200mg/m 2 Intravenous infusion in 250ml sodium Day 8 Prednisolone 100mg Oral 30 minutes prior to rituximab Chlorphenamine 10mg Intravenous bolus 30 minutes prior to rituximab Hydrocortisone 100mg Intravenous bolus 30 minutes prior to rituximab Paracetamol 1g Oral 30 minutes prior to rituximab Rituximab 375mg/m 2 Intravenous infusion in 500ml sodium chloride 0.9% Vincristine 1.5mg/m 2 (Maximum Intravenous infusion in 50ml sodium chloride 0.9% over 5-10 minutes 2mg) Metoclopramide 10mg Oral four times daily as required AUTHORISED BY Dr J Addada PAGE 2 of 8

3 Day 9 Hydration prior to high dose methotrexate See separate protocol High dose methotrexate for more details Day 10 Ondansetron 8mg Oral or intravenous pre-chemotherapy High dose Methotrexate 65 years 3000mg/m 2 65 years 1000mg/m 2 See separate protocol High dose methotrexate for more details Metoclopramide 10mg Oral four times daily for 2 days, then as required Day 11 Folinic acid rescue Day 13 G-CSF (Filgrastim ) 300 micrograms Subcutaneous injection once daily, until neutrophils > 1.0 x 10 9 /L Day 15 Methotrexate 12.5mg Intrathecal injection Day 16 Folinic Acid 15mg Oral as a single dose, 24 hours after the intrathecal methotrexate Frequency & duration: The next cycle of treatment (R-CODOX-M or R-IVAC) should commence when neutrophils > 1.0 x 10 9 /L and platelets (unsupported) > 75 x 10 9 /L. Notes: High dose methotrexate See separate protocol High dose methotrexate. This should only be given in the presence of a normal serum creatinine and a measured creatinine clearance of > 50 ml/min/m 2. Prescribing and administration of intrathecal (IT) drugs Whilst the LY10 trial protocol stated that the first intrathecal dose should be given on day 1, in order to reduce the risk of misadministration, the intrathecal dose has been moved to day 0 to separate it from the IV vincristine dose due on day 1. Please note that in accordance with Health Service Circular HSC 2008/001, national guidance on the safe administration of intrathecal chemotherapy must be followed. AUTHORISED BY Dr J Addada PAGE 3 of 8

4 For more details of steps taken locally to implement this guidance please refer to the Trust policy for the administration of intrathecal chemotherapy. Where CODOX-M starts on either a Thursday or a Friday, the day 3 intrathecal cytarabine is due during the weekend. In these cases, the day 3 intrathecal dose should be delayed until the Monday. Baseline investigations Cardiac assessment (e.g. MUGA) in those patients 65 years or those with a cardiac history. Rituximab This section should be read in conjunction with the Guidelines for the administration of Rituximab. 1. 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. Premedication consisting of 100mg prednisolone orally given 30 minutes before rituximab should be given on cycle 1 in addition to the normal premedication listed above. If the patient develops a severe febrile reaction to rituximab, consider giving 100mg prednisolone prior to rituximab in subsequent cycles. 2. Rituximab doses should be rounded to the nearest 100mg. 3. Use rituximab rate calculator to assist with rate escalation of rituximab infusion. Only when the patient has successfully received a full dose of rituximab at the licensed rate should infusion by the rapid rate be considered. 4. 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. Accelerate the infusion rate more slowly as tolerated by the patient. AUTHORISED BY Dr J Addada PAGE 4 of 8

5 Dose modifications and toxicities 1. Haematological toxicity There are no dose modifications based upon the degree or duration of myelosuppression. 2. Renal impairment Cyclophosphamide GFR ml/min Dose >20 100% % <10 50% Dose reduction for renal impairment is not required for doxorubicin or vincristine. Tumour Lysis For the prevention of acute tumour lysis syndrome refer to local policy; if at risk use rasburicase. The recommended dose is 0.20 mg/kg/day. Rasburicase is administered as a once daily 30 minute intravenous infusion in 50 ml of a sodium chloride 0.9% solution. Repeated doses may be required. Hydration will also be commenced immediately at a rate of 4.5 litres/m 2 /day or as close to this figure as tolerated. Sodium content should be at least 75mmol/L (equivalent to 0.45% N/Saline & Dextrose 5% infusion). Furosemide should be used as needed to ensure that output is consistent with intake. Potassium should not be added to infusions prior to, or during, the first few days of therapy unless potassium drops below 3.0 mmol/l. Sodium bicarbonate should be added to IV solutions in the presence of an elevated uric acid (normally mmol of bicarbonate per litre of fluid will be administered). Urine ph should be maintained at 7.0 or above. All bicarbonate should be removed from IV solutions as soon as plasma uric acid is within the normal range or serum bicarbonate >30 mmol/l and/or immediately prior to the commencement of chemotherapy. AUTHORISED BY Dr J Addada PAGE 5 of 8

6 Intensive post chemotherapy biochemical monitoring is mandatory in patients with bulky disease and should be considered in all patients during the first 3-5 days of treatment. Serum electrolytes, creatinine, calcium and phosphorous may need to be measured up to every 4-6 hours in patients with bulky disease. Occasionally patients present with established renal failure, requiring dialysis. In patients with extensive Burkitt's or Burkitt's-like lymphoma, profound metabolic disturbances may occur shortly after commencing chemotherapy, largely as a result of tumour lysis. The possible changes are as follows: a. Hyperkalaemia This is rare. It can occur within a few hours of commencement of chemotherapy and close surveillance should be maintained in patients with large tumour burdens or any evidence of renal impairment. Serial K+ levels, e.g. 2 hourly if renal function markedly impaired, supplemented by serial ECGs are mandatory in such patients and ideally, careful cardiac monitoring for the first hours of treatment should be carried out. Further surveillance should be based on needs dictated by the clinical course. b. Elevated urea and creatinine Blood urea may begin to rise within 24 hours of commencement of therapy. This will be followed shortly after by elevations in plasma creatinine. Elevations of urea and creatinine may persist for 7-10 days. Urea and creatinine should be monitored 4 to 6 hourly during the first 72 hours of therapy in patients with a large tumour burden, prior renal impairment or raised serum uric acid level. c. Hyperphosphataemia and Hypocalcaemia Changes in phosphate and calcium levels usually occur shortly after the earliest rise in blood urea is detected. Marked hyperphosphataemia, as a result of the release of intracellular phosphate, may be sufficient to induce intraluminal renal tubular precipitation of phosphates that may cause oliguria and worsen azotemia. It should be noted that phosphate solubility is decreased at an alkaline ph; hence alkalinisation of the urine is normally stopped prior to chemotherapy. Hypocalcaemia secondary to hyperphosphataemia may cause potentially fatal cardiac arrhythmias. Calcium and phosphate levels should be monitored carefully (e.g. 4-6 hourly) especially during the first hours of therapy. Patients with relative oliguria, azotemia or tumour involvement of the renal tract are at a particular risk for the development of the serious consequences such as anuria (phosphates), tetany or cardiac arrhythmias (hypocalcaemia). AUTHORISED BY Dr J Addada PAGE 6 of 8

7 3. Hepatic impairment Doxorubicin Bilirubin micromol/l Dose <20 100% % % >85 contraindicated Or AST Units/L Dose 2-3x ULN 75% >3x ULN 50% Vincristine Bilirubin AST/ALT micromol/l Units/L Dose or % >51 & normal 50% >51 & >180 omit 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 (max 10mg). For higher grade toxicity omit. *NCI Common Toxicity Criteria Grade Toxicity Neutrophils <0.5 x 10 9 /l Platelets x 10 9 /l <10 AUTHORISED BY Dr J Addada PAGE 7 of 8

8 Neuropathy (motor) Neuropathy (sensory) Subjective weakness but no objective findings Loss of deep tendon reflexes or parasthesia (including tingling) but not function Mild objective weakness function, but not interfering with activities of daily living Objective sensory loss or parasthesia (including tingling) function, but not interfering with activities of daily living Objective weakness activities of daily living Sensory loss or parasthesia activities of daily living Paralysis Permanent sensory loss that interferes with function Supportive care 1. Rasburicase 0.20 mg/kg/day if there is high risk of tumour lysis. The dose may need to be repeated for several days. 2. All patients should receive Pneumocystis jirovecii and antiviral prophylaxis throughout treatment: Dapsone 100mg daily. (Note that cotrimoxazole should not be given due to the potential for interaction with methotrexate). Aciclovir 400mg twice daily. 3. GCSF 300 micrograms once daily by subcutaneous injection from day 13 until neutrophils > 1.0x10 9 /L. References 1. LY10 Trial Protocol 2. Using Vinca Alkaloid Minibags (Adults/Adolescent Units); NPSA Rapid Response Alert 4; 11 August 2008 AUTHORISED BY Dr J Addada PAGE 8 of 8