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3 Multiple Myeloma 3.10 Regimen name: Thalidomide (+/- pulsed dexamethasone) Indications Non-intensive treatment, Relapsed or refractory myeloma, Maintenance therapy Pre-treatment Evaluation Document FBC (with film), plasma viscosity, U&E, creatinine, LFTs, calcium, glucose, serum free light chain measurements, serum protein electrophoresis and paraprotein quantitation, CRP, 2-microglobulin and immunoglobulin levels. Urine for BJP (and formal evaluation of 24 hour urinary BJP excretion if light chain only myeloma). Bone marrow aspirate ± trephine (and cytogenetics if part of local protocol). Skeletal survey. Document WHO performance status of patient. Document height and weight and surface area. Consider ECG ± echocardiogram if clinical suspicion of cardiac dysfunction. Give adequate verbal and written information for patients and relatives concerning patient’s disease, treatment strategy and side effects. Obtain written consent from patient or guardian. Drug Regimen Drug (OPCS code: X70.5) Day Dose Route 100mg – 200mg daily for PO Continuously Thalidomide 2 weeks, increasing by 50mg every week up to 800mg daily if tolerated See Concurrent Medication section for Dexamethasone dosing. MAINTENANCE DOSING Drug Dose 50mg daily for 4 weeks, Continuously Thalidomide increasing to 100mg daily if tolerated Day Route PO Comments At night Comments At night Considerations Incidence of thromboembolic events increases when thalidomide is given in combination with dexamethasone and/or chemotherapy. Incidence of VTS occurring with single agent thalidomide is <5%. For more information consult the UKMF/BCSH Guidelines www.ukmf.org.uk/guidelines/thalidomide. Thalidomide is a known teratogenic agent. 841019660 Page 1 of 3 The conditions of a Pregnancy Prevention Programme must be fulfilled for all patients unless there is reliable evidence that the patient does not have childbearing potential. A female patient or a female partner of a male patient is considered to have childbearing potential unless she meets at least one of the following criteria: 1. • Age 50 years and naturally amenorrhoeic for 1 year* 2. • Premature ovarian failure confirmed by a specialist gynaecologist 3. • Previous bilateral salpingo-oophorectomy, or hysterectomy 4. • XY genotype, Turner syndrome, uterine agenesis. *Amenorrhoea following cancer therapy does not rule out childbearing potential. For women of childbearing potential, thalidomide is contraindicated unless all of the conditions of a Pregnancy Prevention Programme (PPP) are met Thalidomide must be discontinued and all supplies returned if the patient or a male patient’s partner becomes pregnant or pregnancy is suspected (positive pregnancy test). If using the Pharmion brand, this should then be reported to the Pharmion Risk Management Centre. Cycle Frequency Continuous Dose Modifications If a thromboembolic event eg.DVT or PE occurs the thalidomide should be stopped until good anticoagulant control is established using standard treatment guidelines. The thalidomide may be restarted, as long as there are no other adverse events, at 50mg daily, increasing to maximum tolerated dose if anticoagulant control remains stable and there are no other adverse events. Grade 3 – 4 toxicity of any of the major adverse effects (constipation, neuropathy, fatigue, sedation, rash, tremor and oedema) would necessitate; - stopping the thalidomide until adverse event resolved, - reintroduce at 50mg daily, - escalate to maximum tolerated dose. Investigations prior to subsequent cycles FBC, U&E, creatinine, LFTs, paraprotein level or urinary protein/BJP excretion, plasma viscosity. Reassess disease response after each cycle, and then 6 weekly during plateau phase. Treatment duration Until disease progression 841019660 Page 2 of 3 Concurrent Medication Allopurinol 300mg (or 100mg if creatinine clearance <20mls/min) od po during the first month. Dexamethasone (if used) 20-40mg daily for 4 days every 2-4 weeks. Reduced sideeffects are seen with 20mg dose. H2-antagonist or PPI is advised for patients receiving Dexamethasone. Consider oral systemic anti-bacterial, anti-viral and/or anti-fungal prophylaxis if patient is neutropenic - refer to local protocol. Bisphosphonates Anti-emetics This regimen has mild emetic potential Adverse Effects See patient information References Singhal S, Mehta J, Desikan R et al. Antitumor activity of Thalidomide in refractory multiple myeloma. NEJM 1999; 341: 1565-1571. Barlogie B, Desikan R, Eddleman P et al. Extended survival in advanced and refractory myeloma after single agent Thalidomide: identification of prognostic factors in a Phase 2 study of 169 patients. Blood 2001; 98: 492-494. Durie BGM & Stepan DE. Low dose Thalidomide alone and in combination: longterm follow-up. Blood 2001; 98 (Suppl 1): 163a. Wechalekar AD, Sutton D, Voralia et al. Intermediate dose Thalidomide (200 mg daily) has comparable efficacy and less toxicity than higher doses in relapsed multiple myeloma. Blood 2001; 98 (Suppl 1): 162a. Weber DM, Gavino M, Delasalle K et al. Thalidomide alone or with Dexamethasone for multiple myeloma. Blood 1999; 94 Suppl 1: 604a. Rajkumar SV, Hayman SR, Gertz MA et al. Combination therapy with Thalidomide plus Dexamethasone (THAL/DEX) for newly diagnosed myeloma. Blood 2001; 98 (Suppl 1): 849a. Patient Information http://www.macmillan.org.uk/Cancerinformation/Cancertreatment/Treatmenttypes/Biolo gicaltherapies/Angiogenesisinhibitors/Thalidomide.aspx http://www.macmillan.org.uk/Cancerinformation/Cancertreatment/Treatmenttypes/Supp ortivetherapies/Steroids.aspx Written/ revised by: Dr S Abdalla, Stephanie Kirschke, Pauline McCalla and Dr A Rahemtulla Authorised by: WLCN Haematology TWG September 2009 Date for review by Haematology TWG: September 2010 841019660 Page 3 of 3