R-FC for Chronic Lymphocytic Leukaemia LKWOS-005/01

Transcription

1 West of Scotland Cancer Network Chemotherapy Protocol R-FC for Chronic Lymphocytic Leukaemia LKWOS-005/01 Indication B cell Chronic Lymphocytic Leukaemia First line therapy in patients under 70 years of age. Eligibility Inclusion criteria Patients with Binet stage A progressive, stage B and C disease Patients with bulky lymphadenopathy, night sweats or weight loss Exclusion criteria Renal impairment with a calculated creatinine clearance <30ml/min A history of or current autoimmune haemolytic anaemia/thrombocytopenia. Treatment Intent Palliative Pre-treatment evaluation Informed consent, provision of verbal and written information. Refer to investigations outlined in the clinical management guideline for CLL. Height, weight and body surface area calculation. Regimen Drug Dose Route Administration Day to be given Rituximab 375mg/m2 for cycle 1 IV Infuse as per SPC Day 1 but see below* only then 500mg/m2 thereafter* 40mg/m 2 PO Once daily Days 1-3 Cyclophosphamide 250mg/m 2 PO Once daily Days 1-3 * For CLL patients whose lymphocyte count is > 25 x 10 9 /L then it is recommended to fractionate the rituximab dose over 2 days. For cycle one this would be 50mg/m 2 on day 0 followed by 325mg/m 2 on day 1 (i.e. total dose of 375mg/m 2 ). If the lymphocyte count is still >25 x 10 9 /L by cycle 2 then give give 125mg/m 2 on day 0 then 375mg/m 2 on day 1 (i.e. total dose 500mg/m 2 ) Page 1 of 5

2 Rituximab Infusion schedule Recommended pre medication consists of paracetamol 1g PO, chlorphenamine 10mg IV & hydrocortisone 100mg IV. Hydrocortisone use is optional in the SPC however routine use is recommended based on local clinical experience. First infusion: Initiate at 50mg/hr; after the first 30minutes if tolerated increase the rate by 50mg/hr increments every 30minutes to a maximum of 400mg/hr. Subsequent infusions: Initiate at 100mg/hr; if tolerated increase the rate by 100mg/hr increments every 30minutes to a maximum of 400mg/hr. NB. The rapid infusion method for rituximab should not be used until there is further data on the safety of this approach in CLL patients 10mg tablets Calculated total daily dose based on BSA. Dose rounded up or down to multiple of 10mg Take tablets on an empty stomach or with food Swallow whole with water Cyclophosphamide 50mg tablets Calculated total daily dose based on BSA. Dose rounded up or down to multiple of 50mg Swallow tablets whole on an empty stomach. Take with meals if gastric irritation is severe Take tablets early in the day if possible, ensure patient well hydrated Intravenous doses (If oral route not available) Drug Dose Route Administration Day to be given 25mg/m 2 IV Infusion over 30 Days 1-3 minutes Cyclophosphamide 250mg/m 2 IV Bolus via fast running drip Days 1-3 Treatment repeated every 28 days. Normally 3 to 6 cycles required for maximal response. Supportive therapy Allopurinol 300mg daily (100mg if CrCl<20ml/min) for cycles 1 and 2 unless contraindicated Oral Co-trimoxazole for PCP prophylaxis (unless contraindicated), throughout treatment and for up to 6 months after completion Aciclovir 400mg bd daily if history of VZV or Herpes simplex infection Antiemetic cover with domperidone 20mg qds for 5 days. Emetogenic Risk Low (10-30%), refer to local anti-emetic policy for management but see note above. Page 2 of 5

3 Adverse effects Very Common (>1 in 10) Common (>1 in 100, <1 in 10) Infections and infestations: bacterial Infections and infestations: sepsis, infections, viral infections,bronchitis, pneumonia, febrile infection, herpes zoster, Opportunistic infections (like latent viral respiratory tract infection, fungal infections, reactivation, e.g. Progressive multifocal infections of unknown aetiology, acute leukoencephalopathy, Herpes zoster virus bronchitis, sinusitis Epstein-Barr-virus), pneumonia Blood and lymphatic system disorders: Blood and lymphatic system disorders: anaemia, thrombocytopenia, pancytopenia neutropenia, leucopenia,febrile Nervous system disorders: paraesthesia, neutropenia hypoaesthesia, agitation, insomnia, Immune system disorders: infusion vasodilatation, dizziness, anxiety related reactions, angioedema Gastrointestinal disorders: vomiting, Skin and subcutaneous tissue diarrhoea, abdominal pain, dysphagia, disorders: pruritus, rash, alopecia stomatitis, constipation, dyspepsia, General disorders and administration anorexia, throat irritation site conditions: fever, chills, asthenia, Musculoskeletal, connective tissue and headache bone disorders: hypertonia, myalgia, arthralgia, back pain, neck pain, pain Neoplasms benign, malignant and unspecified (incl cysts and polyps): Myelodysplastic syndrome and Acute Myeloid Leukaemia (mainly associated with prior, concomitant or subsequent treatment with alkylating agents, topoisomerase inhibitors or irradiation) Nervous system disorders: peripheral neuropathy For more detailed information please refer to the current Summary of Product Characteristics Extravasation risk category: Drug Rituximab Cyclophosphamide Category Precautions & contraindications Hypersensitivity to active substance or any of excipients Pregnancy or breast feeding Haemorrhagic cystitis Renal impairment with creatinine clearance < 30ml/min (see table below) Treatment with fludarabine is contraindicated in patients with a history of or current autoimmune haemolytic anaemia/thrombocytopenia. Patients with a positive Coombs test but without other evidence of active haemolytic anaemia can be treated but require careful monitoring. Patients should not be treated with fludarabine in the presence of active infection. /continued over Page 3 of 5

4 If patients develop infection, requiring admission to hospital, following fludarabine therapy the clinician should carefully consider whether continued treatment with this agent is necessary/justified. Patients found to have a 17p deletion by FISH on prognostic evaluation. Contraceptive measures should be taken during and for at least 6 months after cessation of therapy Avoid breast feeding during treatment Avoid live vaccines during and after treatment : All cellular blood components should be irradiated for 1 year after therapy to prevent transfusion associated graft versus host disease Investigations prior to subsequent cycles Weight recalculate BSA if weight change +/- 10% from baseline FBC, DCT, retics, U+E, LFT, LDH. Performance status Assessment of toxicity documented using Common Toxicity Criteria Dose modifications Haematological The haematological assessment needs to be made in relation to these parameters pre treatment. Normally the Hb level and Plt count should improve by the start of the next cycle. The WBC should obviously fall. Result Value Action Platelets x 10 9 /L <100 Delay treatment up to maximum of 2 weeks, then if <100, consider dose reduction WCC NA Neutrophils <1X10 9 /L Delay treatment up to maximum of 2 weeks, then if <100, consider dose reduction. Consider stopping co-trimoxazole. Grade 4 neutropenia with sepsis Renal Full reassessment of patient circumstances. Consider GCSF Drug GFR % of full dose Comments 30-70ml/min 50% <30ml/min Contra-indicated Cyclophosphamide 10-50ml/min 75% <10ml/min 50% Hepatic Drug Bil AST/ALT % of full dose Comments No dose changes are recommended Cyclophosphamide >17 2/3x ULN Not recommended As per SPC Clinical decision Page 4 of 5

5 Others Toxicity Grade Action Tumour lysis syndrome Refer to local protocol. Consider rasburicase Evaluation of response to treatment Evaluation of reduction of WBC (after each cycle). Evaluation of resolution of anaemia or thrombocytopenia in stage C patients. Full general examination to assess for resolution of lymphadenopathy and splenomegaly (after each cycle). Imaging with CT may be necessary, after 3 cycles, to assess resolution of symptomatic deep abdominal lymphadenopathy. Refer to Consultant if little evidence for response after any cycle or on suspicion of autoimmune haemolytic anaemia/thrombocytopenia. References 1. Rituximab for first line treatment of CLL in combination with fludarabine and cyclophosphamide SMC 540/09 2. Catovsky D et al. Assessement of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 Trial): a randomised controlled trial. Lancet 2007; 370: Summary of Product Characteristics for rituximab, fludarabine and cyclophosphamide accessed at Document control Prepared by Jonathan Allan Checked by Dr Mike Leach, Dr Pam McKay Approved by RCAG Prescribing Advisory Subgroup Issue date August 2009 Review date August 2011 Reference/version no. LKWOS-005/01 Replaces Not applicable Page 5 of 5