CEPP for Diffuse Large B Cell Lymphoma (LYMWOS005/1)

Transcription

1 West of Scotland Cancer Network Chemotherapy Protocol CEPP for Diffuse Large B Cell Lymphoma (LYMWOS005/1) Indication First line treatment of Diffuse Large B Cell Lymphoma (DLBCL) in patients who are unfit for CHOP. Second line treatment in patients unfit for more aggressive salvage therapy. Eligibility Criteria Confirmed diagnosis of DLBCL. Treatment intent Curative. Pre-treatment evaluation 1. Full staging tests. 2. Assessment of patients Performance status. 3. Provision of verbal and written information. 4. Informed consent 5. HepB, Hep C and HIV status. 6. Height, weight and BSA. 7. Baseline investigations FBC, U&E s, LFT s, LDH Creatinine clearance Page 1 of 5

2 Regimen Drug Dose Route Administration Frequency Treatment Days Cyclophosphamide 600mg/m 2 IV Injection into the side arm of a fast flowing infusion of NaCl 0.9%. 70mg/m 2 IV Infusion over 45 minutes in ml NaCl (available as 50 or 100mg capsules) Procarbazine (available as 50mg capsules) Once daily Days 1 & 8 N/A Once daily Day 1 N/A 0.9%. 140mg/m 2 Oral * Once daily Days 2 & 3 N/A 60mg/m 2 Oral Once daily Days 1-10 N/A Prednisolone 60mg/ m 2 Oral Once daily Days 1-10 N/A Maximum Cumulative dose Repeat every 28 days for 6-8 cycles. * Please note that the original article used as reference for this regimen quotes an IV dose for etoposide on days 2 and 3. However it was felt that this should be converted to an oral dose to allow the regimen to be given in a day case setting. Supportive therapy Emetogenic risk: Low (10-30%), with the exception of days 1 & 8, where it is Moderate (30-90%) Refer to local guidelines for management. Allopurinol 300mg daily for 7 days (100mg if CrCl < 20ml/min) for cycles 1 & 2 unless contraindicated. Mouthcare as per local policy Consider PPI with each course (with prednisolone). GCSF primary prophylaxis is not routinely indicated. GCSF secondary prophylaxis may be considered, see haematological toxicities. Adverse effects Very Common Incidence > 10% Common Incidence 1-10% Cardiovascular: hypotension. Haematological: myelosuppression (anaemia, thrombocytopenia, neutropenia) Gastrointestinal: nausea/vomiting, mucositis, stomatitis, increased appetite, dyspepsia, anorexia. Genitourinary: haemorrhagic cystitis, urinary fibrosis. Skin: alopecia, hyperpigmentation, rash. Central nervous system: insomnia, nervousness. Cardiovascular: facial flushing. Respiratory: nasal congestion. Gastrointestinal: diarrhoea, abdominal pain. Central nervous system: headache. Endocrine: diabetes, glucose intolerance. Page 2 of 5

3 This is not an exhaustive list. Please refer to SPC, at for more detailed information. Extravasation risk category: Drug Cyclophosphamide Category Neutral Irritant In the event of an extravasation, refer to local policy. Precautions & contraindications Drug interactions Known allergy to any of the drug regimen. Contraindicated in pregnancy and breastfeeding. Cyclophosphamide is contraindicated in patients with urinary tract infections or with acute urothelial toxicity from cytotoxic chemotherapy or radiotherapy. Caution in renal impairment for cyclophosphamide, etoposide and procarbazine. Caution in hepatic impairment for cyclophosphamide, etoposide and procarbazine. Procarbazine is a weak monoamine oxidase inhibitor (MAOI) and may interact with other drugs, alcohol and certain foods (containing tyramine). Drug Increased Effect / Toxicity Decreased Effect Cyclophosphamide Aminoglutethimide, carbamazepine, chloramphenicol, nafcillin, nevirapine, phenobarbital, phenytoin, rifamycins, thiazide diuretics and other inducers of CYP2B6 or CYP3A4. Azole antifungals, ciprofloxacin, clarithromycin, desipramine, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone, nicardipine, paroxetine, propofol, protease inhibitors, quinidine, sertraline, verapamil and other inhibitors of CYP2B6 or CYP3A4. Procarbazine Azole antifungals, calcium antagonists, ciclosporin, ciprofloxacin, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine, verapamil. may increase the levels/effects of warfarin and methotrexate. Sympathomimetic amines (ephedrine and amphetamines), tricyclic antidepressants, Cyclophosphamide may decrease digoxin levels. Aminoglutethamide, carbamazepine, nafcillin, nevirapine, phenobarbital, phenytoin, rifampicin, St. John s wort. Page 3 of 5

4 barbiturates,phenothiazines, alcohol, tyramine containing foods. Investigations prior to subsequent cycles 1. FBC, U&E s, LFT s. 2. Creatinine clearance. 3. Performance status. 4. Assessment of toxicity, documented by CTCAE version Weight (Re-calculate surface area if > 10% change from baseline). 6. Full physical examination. Dose modifications Haematological Result Value Action Platelets x 10 9 /L < 100 Delay Neutrophils < 1.0 Delay Grade 4 neutropenia with sepsis. Consider GCSF. Renal Drug GFR % of full dose Comments Cyclophosphamide >50 100% % <10 50% >60 100% % % % < 15 50% Susequent doses should be Based on clinical response. Procarbazine 50% If serum creatinine >177umol/L <10 Not recommended Hepatic Drug Bil AST/ALT % of full dose Comments Cyclophosphamide In the absence of jaundice, no dose adjustment required ULN-51 Or AST % > 51 Or AST > 180 Clinical decision Procarbazine > 50 50% >85 Or AST > 180 Omit dose Evaluation of response to treatment Repeat initial staging tests after 4 cycles. Page 4 of 5

5 References 1. Chao NJ, Rosenberg SA and Horning SJ. CEPP(B): An Effective and Well- Tolerated Regimen in Poor-Risk, Aggressive Non-Hodgkin s Lymphoma. Blood 1990 Oct 1; 76(7): The North London cancer Network. Dosage Adjustments for Cytotoxics in Hepatic Impairment. Nov The North London cancer Network. Dosage Adjustments for Cytotoxics in Renal Impairment. Nov Salimando DA.Drug Information Handbook for Oncology. 4 th ed: Ohio: Lexi- Comp; Allwood M, Stanley A, Wright P. The Cytotoxic Handook. 4 th ed. Oxon: Radcliffe Medical Press; Kris MG, Hesketh PJ, Somerfield MR et al. American Society of Clinical Oncology Guidelines for Antiemetics in Oncology: Update JCO 2006; 24(18): Summary of Product Characteristics for Bleomycin, chlorambucil, doxorubicin, etoposide, procarbazine, vinblastine and vincristine. January BNF 52. Document control Prepared by Craig Richardson & Kelly Baillie Checked by Dr L. Mitchell & Dr P. Tansey Approved by Pam McKay, lead Clinician Haemato-oncology MCN Issue date October 2008 Review date October 2010 Reference/version no. LYMWOS005/1 Replaces Not applicable Page 5 of 5