Myeloma group

CHEMOTHERAPY PROTOCOL: ORAL CYCLOPHOSPHAMIDE WITH OR WITHOUT PREDNISOLONE

Summary of changes (2013): Tabulation of dose modification

INDICATION First line or end stage treatment for patients treated with a palliative approach. Suitable alternative to melphalan particularly if blood counts are below the required level. PRE-ADMINISTRATION 1. Ensure all the following staging investigations are done: o FBC & film o Clotting screen o U&Es o LFTs o Calcium o Albumin o Uric acid o CRP o Urine collection for creatinine clearance (CrCl), total protein, light chain (Bence Jones) o Electrophoresis and immunofixation for quantitation of serum paraprotein and immunoglobulins. o Serum free light chain assay (Freelite) o !2 microglobulin o Group and save o Skeletal survey (skull, whole spine, pelvis, all proximal limbs, CXR) o MRI if suspicion of spinal cord compression, or significant pain present in the absence of plain Xray changes o Bone marrow aspirate and trephine (with immunophenotyping for kappa/lambda if appropriate) Additional investigation: o Plasma viscosity if hyperviscosity suspected 2. Patient should be well hydrated, aim for 3 litres a day. 3. Record height and weight. 4. Consent - ensure patient has received adequate verbal and written information regarding their disease, treatment and potential side effects. Document in medical notes all the information that has been given and that patient consent has been obtained. This is a controlled document and therefore must not be changed or photocopied 1 of 3 Cyclophosphamide Authorised by Myeloma Published: May 2008 Version - oral lead Revised: Jan & March 2009, 4.0 Dr. Karthik Ramasamy March 2010 Reviewed: June 2011 Revised: Aug 2012, June 2013 Review: 2014

Myeloma group

DRUG REGIMEN Cyclophosphamide 300 mg/m2 (rounded down to nearest 50 mg) once per week orally or 50-100 mg oral daily, continuously WITH OR WITHOUT Prednisolone 20 mg daily orally for 6 weeks and then tailed off over subsequent 2 weeks NB: Cyclophosphamide tablets are 50 mg in strength. Prednisolone tablets are 5 mg and 25 mg in strength. CYCLE FREQUENCY Continue until plateau phase (paraprotein level stable for 3 months) then stop. DOSE MODIFICATIONS 2 Renal Clinical decision GFR > 20ml/min 100% dose GFR 10 20ml/min 75% dose GFR < 10ml/min 50% dose Hepatic Exposure to active metabolites may not be increased, suggesting that dose reduction may not be necessary. Clinical decision.

Dose should be modified if severe myelotoxicity occurs. INVESTIGATIONS - First and subsequent cycles FBC. U&Es, creatinine, glucose, calcium. ADDITIONAL INVESTIGATIONS - Alternate cycles Serum electrophoresis with paraprotein and immunoglobulin quantification. Serum free light chains in light chain or non-secretory myeloma. OTHER INVESTIGATIONS Consider repeat BM aspirate and trephine after 3 or 4 months in non-secretory myeloma. CONCURRENT MEDICATIONS Allopurinol 300 mg daily for 7 days. Proton pump inhibitor with steroids. Consider fluconazole if steroid related side effects develop. Bisphosphonates as per protocol.

This is a controlled document and therefore must not be changed or photocopied 2 of 3 Cyclophosphamide Authorised by Myeloma Published: May 2008 Version - oral lead Revised: Jan & March 2009, 4.0 Dr. Karthik Ramasamy March 2010 Reviewed: June 2011 Revised: Aug 2012, June 2013 Review: 2014

Myeloma group

EMETIC RISK Moderate emetic risk. Anti-emetics may only be required on the days cyclophosphamide is taken. REFERENCES
1. Smith A, Wisloff F, Samson D; UK Myeloma Forum; Nordic Myeloma Study Group; British Committee for Standards in Haematology. Guidelines on the diagnosis and management of multiple myeloma 2005. Br J Haematol. 2006 Feb;132(4):410-51. 2. Bunn & Ashley, UK Renal Pharmacy Group. The renal drug handbook 3rd Edition.

This is a controlled document and therefore must not be changed or photocopied 3 of 3 Cyclophosphamide Authorised by Myeloma Published: May 2008 Version - oral lead Revised: Jan & March 2009, 4.0 Dr. Karthik Ramasamy March 2010 Reviewed: June 2011 Revised: Aug 2012, June 2013 Review: 2014