The efficacy of the CTD regimen (cyclophosphamide, thalidomide, dexamethasone) in therapy of relapsed and refractory multiple myeloma
Authors:
M. Zemanová 1; V. Ščudla 1; L. Pour 2; E. Gregora 3; P. Pavlíček 3; J. Minařík 1; T. Pika 1; J. Bačovský 1; Z. Adam 2; R. Hájek 2; Pro Českou Myelomovou Skupinu
Authors‘ workplace:
III. interní klinika LF UP a FN Olomouc, 2Interní hematoonkologická klinika FN Brno-Bohunice
a LF MU v Brně, 3Oddělení klinické hematologie FN KV Praha
1
Published in:
Transfuze Hematol. dnes,16, 2010, No. 3, p. 126-132.
Category:
Comprehensive Reports, Original Papers, Case Reports
Overview
Thalidomide has been estimated as a useful drug in the treatment of multiple myeloma in monotherapy or in combinations with steroids and alkylating drugs. The combination of low-dose thalidomide with cyclophosphamide and dexamethasone has shown very good results. In the actual study, authors present the effect, toxicity and results of long-time follow-up of patients treated by the combination of thalidomide, cyclophosphamide and dexamethasone in the „CDT-junior“ regimen for patients up to 65 years (cyclophosphamide 800 mg intravenously on day 1 once a 21-daysę interval, thalidomide 200 mg orally daily and dexamethasone 40 mg orally on days 1–4 and 12–15), and in the „CTD-senior“ regimen for patients over 65 years (cyclophosphamide 50 mg orally daily, thalidomide 100 mg orally daily and dexamethasone 20 mg orally on days 1–4 and 15–18, in a 28-daysę cycle). From the group of 126 patients with progressive form of multiple myeloma or with resistance to conventional chemotherapy, 109 patients were evaluated. Using both modalities of the CTD regimen, objective response was reached in 78 (71.6%) patients, of them complete remission was achieved in 17 (15.6%), very good partial remission in 5 (4.6%) and partial remission in 56 (51.4%) patients. Disease was stabilized in 21 (19.2%) patients, while 10 (9.2%) patients progressed. The toxicity of both regimens was quite low and can be easily managed; weakness, obstipation, neuropathy of lower extremities, glycoregulation worsening and mild leucopenia occured most often. Median of overall survival from the start of the CTD treatment was in the whole group 31.5 months and median of time to progression was 15 months. The difference between „junior“ and „senior“ regimens was not statistically significant. It can be concluded, that the use of thalidomide in both discussed regimens has broaden the therapeutic possibilities in patients with multiple myeloma resistant to conventional chemotherapy.
Key words:
multiple myeloma, resistance to therapy, thalidomide, cyclophosphamide, dexamethasone
Sources
1. Hájek R, Maisnar V, Krejčí M. Thalidomid. Klin Farmakol Farm 2005; 19: 43-46.
2. San Miguel JF. Thalidomide alone or in combination: results in refractory patients. Hematol Rep 2005; 1: 2-6.
3. García-Sanz R, Gonzáles-Fraile MI, Sierra M, et al. The combination of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex) is feasible and can be an option for relapsed/ refractory multiple myeloma. Hematol J 2002; 3: 43-48.
4. García-Sanz R, Gonzáles-Porras JR, Hernández JM, et al. The oral combination of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex) is effective in relapsed/ refractory multiple myeloma. Leukemia 2004; 18: 856-863.
5. Gonzáles-Porras JR, García-Sanz R, Polo-Zarzuela M, et al. ThaCyDex in relapsed/ refractory multiple myeloma. Hematol J 2003; 4, S1: 234.
6. Dimopoulos MA, Hamilos G, Zomas A, et al. Pulsed cyclophosphamide, thalidomide and dexamethasone: an oral regimen for previously treated patiens with multiple myeloma. Hematol J 2004; 5: 112-117.
7. Anagnastopoulos A, Hamilos G, Zomas A, et al. Oral hyperfractionated cyclophosphamide ant intermittent thalidomide-dexamethasone (pulsed CTD) for previously treated patients with multiple myeloma. Hematol J 2003; 4, S1: 235.
8. Kyriakou C, Thomson K, DęSa S, et al. Low-dose thalidomide in combination with oral weekly cyclophosphamide and pulsed dexamethasone is a well tolerated and effective regimen in patients with relapsed and refractory multiple myeloma. Br J Haematol 2005; 129: 763-770.
9. Kropff M, Lang N, Bisping G, et al. Hyperfractionated cyclophosphamide in combination with pulsed dexamethasone and thalidomide (HyperCDT) in primary refractory or relapsed multiple myeloma. Hematol J 2003; 4, S1: 236.
10. Kyriakou C, DęSa S, Fox R, et al. Salvage therapy with cyclophosphamide, dexamethasone and thalidomide (CDT) is a well-tolerated and effective regimen in advanced relapsed/ refractory myeloma. Hematol J 2003; 4, S1: 237.
11. Caravita T, Siniscalchi A, Postorino M, et al. Thalidomide in combination with dexamethasone for relapsed/ refractory multiple myeloma. Hematol J 2003; 4, S1: 238.
12. Di Raimondo F, Pennisi A, Buglio D, et al. Combination of thalidomide, cyclophosphamide and dexamethasone in refractory-relapsed multiple myeloma. Hematol J 2003; 4, S1: 241.
13. Sidra G, Williams CD, Russell NH, et al. Combination chemotherapy with cyclophosphamide, thalidomide and dexamethasone for patients with refractory, newly diagnosed or relapsed myeloma. Haematologica 2006; 91: 862-863.
14. Kropff M, Lang N, Bisping G, et al. Hyperfractionated cyclophosphamide in combination with pulsed dexamethasone and thalidomide (HyperCDT) in primary refractory or relapsed multiple myeloma. Br J Haematol 2003; 122: 607-616.
15. Williams CD, Byrne JL, Sidra G, et al. Combination chemotherapy with cyclophosphamide, thalidomide and dexamethasone achieves a high response rate in patients with newly diagnosed, VAD-refractory and relapsed myeloma. Blood 2004; 104: Suppl., No. 1499.
16. Roussou M, Anagnastopoulos A, Kastritis E, et al. Pulsed cyclophosphamide, thalidomide and dexamethasone regimen for previously treated patients with multiple myeloma: Long term follow up and disease control after subsequent treatments. Leukemia Lymphoma 2007; 48: 754-758.
17. Zemanová M, Ščudla V, Pour L, et al. Režim CTD (cyklofosfamid, thalidomid, dexametazon) v léčbě relabujících a refrakterních forem mnohočetného myelomu. Transfuze Hematol dnes 2007; 13: 126-132.
18. Zemanová M, Ščudla V, Adam Z, et al. Low-dose thalidomide regimens in therapy of relapsed or refractory multiple myeloma. Neoplasma 2008; 55: 349-353.
19. Durie BGM, Harousseau JL, Miguel JS, et al. International uniform response criteria for multiple myeloma. Leukemia 2006; 10: 1-7.
20. Bradwell AR, Mead GP, Carr-Smith HD. Clinical apllications of free light chain assays. Multiple myeloma. In: Bradwell AR, Mead GP, Carr-Smith HD. Serum free light chain analysis. 3rd ed. Birmingham: The Binding Site Ltd. 2005: 67-89.
21. Ščudla V, Minařík J, Schneiderka P, et al. Význam sérových hladin volných lehkých řetězců imunoglobulinu v diagnostice a hodnocení aktivity mnohočetného myelomu a vybraných monoklonálních gamapatií. Vnitř Lék 2005; 51: 1249-1259.
22. Palumbo A, Giaccone L, Bertola A, et al. Low-dose thalidomide plus dexamethasone is an effective salvage therapy for advanced myeloma. Haematologica 2001; 86: 399-403.
23. Palumbo A, Falco P, Ambrosini MT, et al. Thalidomide and dexamethasone is an effective salvage regimen for myeloma patients relapsing after autologous transplant. Blood 2004; 104: Suppl., No. 2396.
24. Boccadoro M, Blade J, Attal M, Palumbo A. The future role of thalidomide in multiple myeloma. Acta Haematol 2005; 114, S1: 18-22.
25. Neuwirtová R, Špička I, Karban J, et al. Naše zkušenosti s léčbou thalidomidem. Transfuze Hematol dnes 2002; 1: 13-19.
26. Zangari M, Anaissie E, Barlogie B, et al. Increased risk of deep-vein thrombosis in patients with multiple myeloma receiving thalidomide and chemotherapy. Blood 2001; 98: 1614-1615.
27. Cavo M, Zamagni E, Cellini C, et al. Deep-vein thrombosis in patients with multiple myeloma receiving first-line thalidomide-dexamethasone therapy. Blood 2002; 100: 2272-2273.
28. Durie BGM, Stepan DE. Low dose thalidomide alone and in combination: long term follow-up. (Abstract 688). Blood 2001; 98 (Suppl. 1): 163.
29. Maisnar V, Radocha J, Büchler T, et al. Monotherapy with low-dose thalidomide for relapsed or refraktory multiple myeloma: Berger response rate with earlier treatment. Eur J Haematol 2007; 79: 305-9.
30. RosiĖol L, Cibeira MT, Bladé J, et al. Extramedullary multiple myeloma escapes the effect of thalidomide. Haematologica 2004; 89: 832-836.
31. Saba S, Epstein A, Niesvizky R, Coleman M. Development of high-grade B-cell neoplasms following thalidomide therapy. Haematologica 2005; 90, S1: 143.
Labels
Haematology Internal medicine Clinical oncologyArticle was published in
Transfusion and Haematology Today
![Issue 3](https://www.prolekare.cz/media/cache/resolve/journal_issue/media/image_pdf/be72e15cc168dd4b3d9353be3f8934e4.jpeg)
2010 Issue 3
Most read in this issue
- Hairy cell leukemia – diagnostics, treatment and monoclonal antibodies
- Follicullar lymphoma and the significance of its tumour microenvironment
- Cytomegalovirus – specific cellular imunity: profile of immune function assesment provides clinically relevant answer
- Immunophenotypic characterization of acute leukemias of ambiguous lineage- new diagnostic entity of the revised WHO classification 2008