RCEOP in Diffuse Large B Cell Lymphoma …

1 Page 1 of 4 WoSCAN CP Ref No.: LYMWOS013/01 Issue Date: August 2009 Review Date: August 2011 West of Scotland Cancer Network Chemotherapy Protocol RCEOP in Diffuse Large B Cell Lymphoma (LYMWOS013/01) Indication First line treatment of Diffuse Large B Cell Lymphoma (includes grade 3b follicular Lymphoma ) in patients not eligible for an anthracycline. Please note: the replacement of doxorubicin with etoposide in this patient group is established local practice in the absence of a definitive reference. Eligibility Inclusion criteria Patients with significant cardiac dysfunction baseline ejection fraction <50%. Patients with borderline cardiac function in the presence of other co-morbidities which may deem them unfit for anthracycline based regimens. Patients who have received or are approaching the maximum cumulative dose of an anthracycline. Treatment Intent Curative Pre-treatment evaluation Informed consent, provision of verbal and written information Assessment of performance status Height, weight and BSA Staging investigations as outlined in CMG If appropriate, discuss the need for contraception in both male and female patients Baseline investigations 1.

2 FBC, U&E s, LFT s,Urate 2. Hep B, Hep C and HIV Regimen Pre-medication required see supportive care section Drug Dose Route Administration Infusion fluid Day to be given Maximum cumulative dose Rituximab 375mg/m2 IV Infuse as per infusion schedule 500ml Sodium Chloride Day 1 only N/A Cyclophosphamide 750mg/m2 IV Bolus via fast running drip N/A Day 1 only N/A Etoposide* 75mg/m2 IV 1hr IV infusion 500mls Sodium Chloride Day 1 only N/A Vincristine (Max 2mg) IV Bolus via fast running drip In 20mls Sodium Chloride Day 1 only N/A Prednisolone 40mg/m2 oral N/A Days 1-5 N/A *Dose Escalation (based on day +10 counts) If the patient does not become neutropenic ( n> )

3 And thrombocytopenic (plts >100) and is deemed fit enough, there is scope to add in oral etoposide 100mg/m2 on days 2 and 3 in subsequent cycles. Page 2 of 4 WoSCAN CP Ref No.: LYMWOS013/01 Issue Date: August 2009 Review Date: August 2011 Rituximab Infusion schedule First infusion: Initiate at 50mg/hr; if tolerated after the first 30minutes, 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. Treatment Schedule Repeat every 21 days for 6-8 cycles Supportive therapy Rituximab: Pre medication of paracetamol 1g po, Chlorphenamine 10mg IV and Prednisolone 40mg/m2 PO (as day one of 5 day course) is required prior to Rituximab administration. Hydrocortisone 100mg IVmay be required for infusion related reactions Allopurinol 300mg (100 mg if CrCl<20ml/min) daily for first two cycles PPI for at least the duration of steroid therapy Aciclovir 400mg twice daily if previous herpes/varicella infection.

4 GCSF primary prophylaxis not routinely recommended; give only if patient has additional risk factors (see GCSF guideline). GCSF secondary prophylaxis may be considered, see haematological toxicities . Prophylactic antibiotics as per local policy Emetogenic Risk Moderate (30-90%) refer to local anti-emetic policy for management Adverse effects Very common (>1in 10) Common (>1 in 100, <1 in 10) Nervous system: fever, chills, headache, pain Skin: rash, pruritus, angiodema, phlebitis, alopecia Gastrointestinal: nausea, GI upset, diarrhoea, constipation, anorexia, mucositis Haematological: lymphopenia, leucopenia, neutropenia, thrombocytopenia Neuromuscular & skeletal: weakness, peripheral neuropathy Respiratory: cough, rhinitis Miscellaneous: infection, night sweats Infusion related reactions: chills, fever, rigors, dizziness, hypertension, myalgia, nausea, pruritus, rash and vomiting. Hypotension with fast etoposide infusion. Endocrine: adrenal suppression Nervous system: Neuropsychiatry effects Renal and Urological Disorders: bladder irritation.

5 Reproductive System and Breast Disorders: , alteration to menstrual cycle and fertility Cardiovascular: dizziness, hypotension, peripheral oedema, hypertension, anxiety, flushing, tachycardia, arrhythmia, orthostatic hypotension, chest pain, cardiotoxicity. Nervous system: agitation, depression, oedema, insomnia, malaise, nervousness, somnolence, vertigo Skin: uritcaria , facial flushing, skin flare at injection, skin and nail changes. Endocrine: hyperglycaemia, hypoglycaemia. Gastrointestinal: diarrhoea, vomiting, weight loss, dyspepsia, dysphagia, stomatitis. Haematolgical: anaemia Local: pain at injection site Neuromuscular & skeletal: arthralgia, back pain, myalgia, arthritis, jaw pain hyperkinesia, hypertonia, hypersthesia, paraesthesia, and headache. Ocular: conjunctivitis, lacrimation disorder Respiratory: throat irritation, bronchospasm, dyspnoea, sinusitis, dyspepsia Miscellaneous: LFT s increased Extravasation risk category: Drug Category Group Rituximab Non-vesicant N/A Cyclophosphamide Neutral 1 Etoposide Irritant 3 Vincristine Vesicant 5 Page 3 of 4 WoSCAN CP Ref No.

6 : LYMWOS013/01 Issue Date: August 2009 Review Date: August 2011 Precautions & contraindications Use with extreme caution in pregnancy but avoid breastfeeding Contraceptive measures should be taken Hypersensitivity to any of the ingredients is a contra- indication Known medicine interactions: Oral hypoglycaemic agents may increase cyclophosphamide concentrations. Metabolism of vincristine may be inhibited by itraconazole. Side effects of cyclophosphamide possibly increased by itraconazole. Prednisolone may increase effects of warfarin. Plasma levels of prednisolone may be affected by some drugs including erythromycin, carbamazepine, primidone,, ritonavir, barbituratres, Avoid concomitant use of clozapine. Digoxin absorption may be reduced. Phenytoin levels may be reduced. Phenytoin may reduce plasma concentration of etoposide. Currently there are limited data on possible drug interactions with rituximab.

7 See Summary of Product Characteristics for full details. Investigations prior to subsequent cycles FBC, U&E, LFTs Performance status Assessment of toxicity, documented using Common Toxicity Criteria version 3 Dose modifications Haematological Result Value Action Platelets x 109/L <100 Consider delaying treatment until platelets recover. If receiving oral etoposide days 2&3, consider omitting, discuss with consultant Neutrophils < Delay treatment until neutrophils recover If receiving oral etoposide days 2&3, consider omitting, discuss with consultant Consider G-CSF, discuss with consultant. Grade 4 neutropenia with sepsis during treatment Consider dose reduction (20% except vincristine) and/or normal dosing with G-CSF support with subsequent cycles discuss with consultant. Renal Drug GFR ml/min % of full dose Comments Cyclophosphamide >50 10-50 <10 100% 75% 50% Consider using Mesna if GFR <50ml/min Etoposide No dose reduction required Vincristine No dose reduction required Rituximab No information on dose reductions Page 4 of 4 WoSCAN CP Ref No.

8 : LYMWOS013/01 Issue Date: August 2009 Review Date: August 2011 Hepatic Drug Bilirubin AST/ALT % of full dose Cyclophosphamide In absence of jaundice, no dose reduction necessary Etoposide >51 2-3 x ULN Contra-indicated Vincristine ULN- 51 >51 >51 60-180 Normal >180 50% 50% Omit Rituximab No information on dose reduction Others Toxicity Grade Action Peripheral neuropathy or/and Constipation 3 4 2 Omit Vincristine Consider 50% of dose of Vincristine, discuss with consultant Nausea and vomiting 1 or above Increase/change anti-emetics.

9 No dose reduction. Grade 3 resolving to grade 1 20% dose reduction depending on toxicity Evaluation of response to treatment in Lymphoma patients CT scan at mid-point of treatment and after completion of treatment if appropriate. Bone marrow trephine if appropriate References 1. The replacement of doxorubicin with etoposide in this patient group is established local practice in the absence of a definitive reference. 2. Coiffier B, Lepage E, BriereJ et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with Diffuse Large -B-cell Lymphoma . NEJM. 346:235-42. 2002. 3. Summary of product characteristics see 4. Summerhayes M, Daniels S. Practical Chemotherapy a multidisciplinary guide. Radcliffe Medical Press, Oxford. 2003 5. Allwood M, Stanley A, Wright P (Eds) The Cytotoxic Handbook. 5th edition. Radcliffe Medical Press, Oxford. 2005 6. Document control Prepared by Jonathan Allan Checked by Lorna Robertson & Dr Julie Gillies Approved by Dr Pam McKay Issue date August 2009 Review date August 2011 Reference/version no.

10 LYMWOS013/01 Replaces Not applicable