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01.05.2005 | Original Article

Combined thalidomide and cyclophosphamide treatment for refractory or relapsed multiple myeloma patients: a prospective phase II study

verfasst von: Sjoerd Hovenga, Simon M. G. J. Daenen, Joost T. M. de Wolf, Gustaaf W. van Imhoff, Hanneke C. Kluin-Nelemans, Wim J. Sluiter, Edo Vellenga

Erschienen in: Annals of Hematology | Ausgabe 5/2005

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Abstract

Thalidomide is an effective agent for patients with refractory multiple myeloma (MM) with a response rate of 30–40% at doses of 200–800 mg but with considerable side effects. We questioned whether lower doses of thalidomide in combination with a daily dose of cyclophosphamide might be an effective regimen with fewer side effects. We included 38 patients with relapsed or refractory MM. The median doses of thalidomide and cyclophosphamide were 100 and 95 mg/day, respectively. Side effects were observed in all patients, with neurotoxicity as the most troublesome. With a median follow-up of 14 months 84% of the patients responded, including 64% partial responses. The median time of progression-free survival was 30 months and the median overall survival time was 20 months. In conclusion, the results demonstrate that the combination of low-dose thalidomide with a daily dose of cyclophosphamide is an effective regimen with a high overall response rate and manageable side effects.

Abdalla SH, Mahmoud S (2003) Thalidomide in relapsed or refractory multiple myeloma: how much and for how long? Leuk Lymphoma 44:989–991CrossRefPubMed

Anagnostopoulos A, Weber D, Rankin K, Delasalle K, Alexanian R (2003) Thalidomide and dexamethasone for resistant multiple myeloma. Br J Haematol 121:768–771CrossRefPubMed

Badros A, Morris C, Zangari M, Barlogie B, Tricot G (2002) Thalidomide paradoxical effect on concomitant multiple myeloma and myelodysplasia. Leuk Lymphoma 43:1267–1271PubMed

Barlogie B, Desikan R, Eddlemon P, Spencer T, Zeldis J, Munshi N, Badros A, Zangari M, Anaissie E, Epstein J, Shaughnessy J, Ayers D, Spoon D, Tricot G (2001) Extended survival in advanced and refractory multiple myeloma after single-agent thalidomide: identification of prognostic factors in a phase 2 study of 169 patients. Blood 98:492–494CrossRefPubMed

Blade J, Samson D, Reece D, Apperley J, Bjorkstrand B, Gahrton G, Gertz M, Giralt S, Jagannath S, Vesole D (1998) Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant. Br J Haematol 102:1115–1123CrossRefPubMed

Blade J, Esteve J (2000) Viewpoint on the impact of interferon in the treatment of multiple myeloma: benefit for a small proportion of patients? Med Oncol 17:77–84PubMed

Celesti L, Clavio M, Poggi A, Casciaro S, Vallebella E, Gobbi M (1997) The association of cyclophosphamide and dexamethasone in advanced refractory multiple myeloma patients. Haematologica 82:351–353PubMed

Chauhan D, Uchiyama H, Akbarali Y, Urashima M, Yamamoto K, Libermann TA, Anderson KC (1996) Multiple myeloma cell adhesion-induced interleukin-6 expression in bone marrow stromal cells involves activation of NF-kappa B. Blood 87:1104–1112PubMed

Chung F, Palmer BD, Muller GW, Man HW, Kestell P, Baguley BC, Ching LM (2003) Effect of 3-fluorothalidomide and 3-methylthalidomide enantiomers on tumor necrosis factor production and antitumor responses to the antivascular agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA). Oncol Res 14:75–82PubMed

10.

Damiano JS, Cress AE, Hazlehurst LA, Shtil AA, Dalton WS (1999) Cell adhesion mediated drug resistance (CAM-DR): role of integrins and resistance to apoptosis in human myeloma cell lines. Blood 93:1658–1667PubMed

11.

De Weerdt O, van de Donk NWCJ, Veth G, Bloem AC, Hagenbeek A, Lokhorst HM (2001) Continuous low-dose cyclophosphamide-prednisone is effective and well tolerated in patients with advanced multiple myeloma. Neth J Med 59:50–56CrossRefPubMed

12.

Garcia-Sanz R, Gonzalez-Porras JR, Hernandez JM, Polo-Zarzuela M, Sureda A, Barrenetxea C, Palomera L, Lopez R, Grande-Garcia C, Alegre A, Vargas-Pabon M, Gutierrez ON, Rodriguez JA, San Miguel JF (2004) The oral combination of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex) is effective in relapsed/refractory multiple myeloma. Leukemia 18:856–863CrossRefPubMed

13.

Gupta D, Li YZ, Li CJ, Hideshima T, Podar K, Davies FE, Raje N, Lentzsch S, Tai YT, Mitsiades C, Mitsiades N, Hayashi T, Chauhan D, Treon SP, Richardson PG, Pardee AB, Anderson, KC (2000) beta-Lapachone demonstrates activity against drug resistant multiple myeloma (MM) cell lines and patient cells. Blood 96:307A

14.

Hanahan D, Bergers G, Bergsland E (2000) Less is more, regularly: metronomic dosing of cytotoxic drugs can target tumor angiogenesis in mice. J Clin Invest 105:1045–1047PubMed

15.

Hideshima T, Chauhan D, Hayashi T, Akiyama N, Mitsiades N, Mitsiades C, Podar K, Munshi NC, Richardson PG, Anderson KC (2003) Blockade of IL-6 triggered signaling cascades by PS-341 (Velcade (R)) via caspase-dependent downregulation of gp130 in multiple myeloma (MM). Blood 102:75A

16.

Hovenga S, de Wolf JT, Guikema JEJ, Klip H, Smit JW, Smit Sibinga CT, Bos NA, Vellenga E (2000) Autologous stem cell transplantation in multiple myeloma after VAD and EDAP courses: a high incidence of oligoclonal serum Igs post transplantation. Bone Marrow Transplant 25:723–728CrossRefPubMed

17.

Juliusson G, Celsing F, Turesson I, Adriansson M, Malm C (1999) Thalidomide frequently induces good partial remission and best response ever in patients with advanced myeloma and prior high dose melphalan and autotransplant. Blood 94:124A

18.

Kees M, Dimou G, Sillaber C, Drach J, Ackermann J, Lechner K, Gisslinger H (2003) Low dose thalidomide in patients with relapsed or refractory multiple myeloma. Leuk Lymphoma 44:1943–1946CrossRefPubMed

19.

Kropff MH, Lang N, Bisping G, Domine N, Innig G, Hentrich M, Mitterer M, Sudhoff T, Fenk R, Straka C, Heinecke A, Koch OM, Ostermann H, Berdel WE, Kienast J (2003) Hyperfractionated cyclophosphamide in combination with pulsed dexamethasone and thalidomide (HyperCDT) in primary and relapsed multiple myeloma. Br J Haematol 122:607–616CrossRefPubMed

20.

Manoharan A (2000) Gentle yet effective treatment for elderly patients with refractory or relapsing multiple myeloma. Am J Hematol 65:81–82PubMed

21.

Moehler TM, Neben K, Benner A, Egerer G, Krasniqi F, Ho AD, Goldschmidt H (2001) Salvage therapy for multiple myeloma with thalidomide and CED chemotherapy. Blood 98:3846–3848CrossRefPubMed

22.

Oakervee HE, McBride NC, Hemmaway CJ (2002) Thalidomide combined with vincristine, adriamycin and dexamethasone (T-VAD) is effective treatment for multiple myeloma and does not prejudice successful stem cell harvesting. Blood 100:402A

23.

Palumbo A, Giaccone L, Bertola A, Pregno P, Bringhen S, Rus C, Triolo S, Gallo E, Pileri A, Boccadoro M (2001) Low-dose thalidomide plus dexamethasone is an effective salvage therapy for advanced myeloma. Haematologica 86:399–403PubMed

24.

Raje N, Hideshima T, Davies FE, Chauhan D, Treon SP, Young G, Tai YT, Avigan D, Gong J, Schlossman RL, Richardson P, Kufe DW, Anderson KC (2004) Tumour cell/dendritic cell fusions as a vaccination strategy for multiple myeloma. Br J Haematol 125:343–352PubMed

25.

Rajkumar SV, Kyle RA (2001) Thalidomide in the treatment of plasma cell malignancies. J Clin Oncol 19:3593–3595PubMed

26.

Rajkumar SV, Hayman S, Gertz MA, Dispenzieri A, Lacy MQ, Greipp PR, Geyer S, Iturria N, Fonseca R, Lust JA, Kyle RA, Witzig TE (2002) Combination therapy with thalidomide plus dexamethasone for newly diagnosed myeloma. J Clin Oncol 20:4319–4323CrossRefPubMed

27.

Richardson PG, Schlossman RL, Weller E, Hideshima T, Mitsiades C, Davies F, LeBlanc R, Catley LP, Doss D, Kelly K, McKenney M, Mechlowicz J, Freeman A, Deocampo R, Rich R, Ryoo JJ, Chauhan D, Balinski K, Zeldis J, Anderson KC (2002) Immunomodulatory drug CC-5013 overcomes drug resistance and is well tolerated in patients with relapsed multiple myeloma. Blood 100:3063–3067CrossRefPubMed

28.

Segeren CM, Sonneveld P, van der Holt B, Vellenga E, Croockewit AJ, Verhoef GE, Cornelissen JJ, Schaafsma MR, van Oers MH, Wijermans PW, Fibbe WE, Wittebol S, Schouten HC, van Marwijk Kooy M, Biesma DH, Baars JW, Slater R, Steijaert MM, Buijt I, Lokhorst HM, Dutch–Belgian Hemato-Oncology Cooperative Study Group (2003) Overall and event-free survival are not improved by the use of myeloablative therapy following intensified chemotherapy in previously untreated patients with multiple myeloma: a prospective randomized phase 3 study. Blood 101:2144–2151CrossRefPubMed

29.

Singhal S, Mehta J, Desikan R, Ayers D, Roberson P, Eddlemon P, Munshi N, Anaissie E, Wilson C, Dhodapkar M, Zeddis J, Barlogie B (1999) Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med 341:1565–1571CrossRefPubMed

30.

Tosi P, Ronconi S, Zamagni E, Cellini C, Grafone T, Cangini D, Pileri SA, Baccarani M, Tura S, Cavo M (2001) Salvage therapy with thalidomide in multiple myeloma patients relapsing after autologous peripheral blood stem cell transplantation. Haematologica 86:409–413PubMed

Titel: Combined thalidomide and cyclophosphamide treatment for refractory or relapsed multiple myeloma patients: a prospective phase II study
verfasst von: Sjoerd Hovenga
Simon M. G. J. Daenen
Joost T. M. de Wolf
Gustaaf W. van Imhoff
Hanneke C. Kluin-Nelemans
Wim J. Sluiter
Edo Vellenga
Publikationsdatum: 01.05.2005
Verlag: Springer-Verlag
Erschienen in: Annals of Hematology / Ausgabe 5/2005
Print ISSN: 0939-5555
Elektronische ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-004-0981-5

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