Melphalan and prednisone plus thalidomide or placebo in elderly patients with multiple myeloma

被引：181

作者：

Waage, Anders ^{[1
,2
]}

Gimsing, Peter ^{[3
,4
]}

Fayers, Peter ^{[2
,5
]}

Abildgaard, Niels ^{[6
]}

Ahlberg, Lucia ^{[7
]}

Bjorkstrand, Bo ^{[8
]}

Carlson, Kristina ^{[9
]}

Dahl, Inger Marie ^{[10
]}

Forsberg, Karin ^{[11
]}

Gulbrandsen, Nina ^{[12
,13
]}

Haukas, Einar ^{[14
]}

Hjertner, Oyvind ^{[2
]}

Hjorth, Martin ^{[15
]}

Karlsson, Torbjorn ^{[16
]}

Knudsen, Lene Meldgaard ^{[17
]}

Nielsen, Johan Lanng ^{[18
]}

Linder, Olle ^{[19
]}

Mellqvist, Ulf-Henrik ^{[20
]}

Nesthus, Ingerid ^{[21
]}

Rolke, Jurgen ^{[22
]}

Strandberg, Maria

Sorbo, Jon Hjalmar ^{[23
,24
]}

Wisloff, Finn ^{[12
,13
]}

Juliusson, Gunnar ^{[25
]}

Turesson, Ingemar ^{[26
]}

机构：

[1] NTNU, St Olavs Hosp, Dept Hematol, N-7006 Trondheim, Norway

[2] Norwegian Univ Sci & Technol, Dept Canc Res & Mol Med, N-7034 Trondheim, Norway

[3] Rigshosp, Dept Hematol, Copenhagen, Denmark

[4] Univ Copenhagen, DK-1168 Copenhagen, Denmark

[5] Univ Aberdeen, Inst Appl Hlth Sci, Aberdeen, Scotland

[6] Odense Univ Hosp, Dept Hematol, DK-5000 Odense, Denmark

[7] Linkoping Univ Hosp, Dept Hematol, S-58185 Linkoping, Sweden

[8] Karolinska Univ Hosp Huddinge, Hematol Ctr, Stockholm, Sweden

[9] Univ Uppsala Hosp, Dept Hematol, Uppsala, Sweden

[10] Univ Tromso Hosp, Dept Med, N-9038 Tromso, Norway

[11] Norrland Univ Hosp, Dept Hematol, Umea, Sweden

[12] Univ Oslo, Fac Med, Oslo, Norway

[13] Ulleval Univ, Dept Hematol, Oslo, Norway

[14] Stavanger Univ Hosp, Dept Med, Stavanger, Norway

[15] Lidkoping Hosp, Dept Hematol, Lidkoping, Sweden

[16] Capio Sankt Gorans Hosp, Dept Internal Med, Stockholm, Sweden

[17] Herlev Hosp, Dept Hematol, Copenhagen, Denmark

[18] Aarhus Univ Hosp, Dept Hematol, DK-8000 Aarhus, Denmark

[19] Orebro Univ Hosp, Dept Med, Orebro, Sweden

[20] Sahlgrens Univ Hosp, Dept Med, S-41345 Gothenburg, Sweden

[21] Haukeland Hosp, Dept Med, N-5021 Bergen, Norway

[22] Kristiansand Hosp, Dept Med, Kristiansand, Norway

[23] Sundsvalls Hosp, Dept Med, Sundsvall, Sweden

[24] Levanger Hosp, Dept Med, Levanger, Norway

[25] Univ Lund Hosp, S-22185 Lund, Sweden

[26] Malmo Univ Hosp, Dept Med, Malmo, Sweden

来源：

BLOOD | 2010年 / 116卷 / 09期

关键词：

PHASE-III; DEXAMETHASONE;

D O I：

10.1182/blood-2009-08-237974

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

In this double-blind, placebo-controlled study, 363 patients with untreated multiple myeloma were randomized to receive either melphalan-prednisone and thalidomide (MPT) or melphalan-prednisone and placebo (MP). The dose of melphalan was 0.25 mg/kg and prednisone was 100 mg given daily for 4 days every 6 weeks until plateau phase. The dose of thalidomide/placebo was escalated to 400 mg daily until plateau phase and thereafter reduced to 200 mg daily until progression. A total of 357 patients were analyzed. Partial response was 34% and 33%, and very good partial response or better was 23% and 7% in the MPT and MP arms, respectively (P < .001). There was no significant difference in progression-free or overall survival, with median survival being 29 months in the MPT arm and 32 months in the MP arm. Most quality of life outcomes improved equally in both arms, apart from constipation, which was markedly increased in the MPT arm. Constipation, neuropathy, non-neuropathy neurologic toxicity, and skin reactions were significantly more frequent in the MPT arm. The number of thromboembolic events was equal in the 2 treatment arms. In conclusion, MPT had a significant antimyeloma effect, but this did not translate into improved survival. This trial was registered at www.clinicaltrials.gov as #NCT00218855. (Blood. 2010;116(9):1405-1412)

引用

页码：1405 / 1412

页数：8

共 15 条

[1] Tools for analyzing multiple imputed datasets [J].

Carlin, John B. ;

Li, Ning ;

Greenwood, Philip ;

Coffey, Carolyn .

STATA JOURNAL, 2003, 3 (03) :226-244

[2] Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99-06): a randomised trial [J].

Facon, Thierry ;

Mary, Jean Yves ;

Hulin, Cyrille ;

Benbouker, Lofti ;

Attal, Michel ;

Pegourie, Brigitte ;

Renaud, Marc ;

Guillerm, Jean Luc Harousseau Gaelle ;

Ahletaix, Carine ;

Dib, Mamoun ;

Voillat, Laurent ;

Maisonneuve, Herve ;

Troncy, Jacques ;

Dervaux, Weronique ;

Monconduit, Mathieu ;

Martin, Claude ;

Casassus, Philippe ;

Jaubert, Jerome ;

Jardel, Henry ;

Doyen, Chantal ;

Kolb, Brigitte ;

Anglaret, Bruno ;

Grosbois, Bernard ;

Yakoub-Agha, Ibrahim ;

Mathiot, Claire ;

Avet-Loiseau, Herve .

LANCET, 2007, 370 (9594) :1209-1218

[3] A systematic review of phase-II trials of thalidomide monotherapy in patients with relapsed or refractory multiple myeloma [J].

Glasmacher, A ;

Hahn, C ;

Hoffmann, F ;

Naumann, R ;

Goldschmidt, H ;

Lilienfeld-Toal, M ;

Orlopp, K ;

Schmidt-Wolf, I ;

Gorschlüter, M .

BRITISH JOURNAL OF HAEMATOLOGY, 2006, 132 (05) :584-593

[4] Interferon-alpha 2b added to melphalan-prednisone for initial and maintenance therapy in multiple myeloma - A randomized, controlled trial [J].

Hjorth, M ;

Westin, J ;

Dahl, IMS ;

Gimsing, P ;

Hippe, E ;

Holmberg, E ;

Lamvik, J ;

Nielsen, JL ;

Lofvenberg, E ;

Palva, IP ;

Rodjer, S ;

Talstad, I ;

Turesson, I ;

Wisloff, F ;

Zador, G ;

AmslerNordin, S ;

Polgary, M ;

Oden, A ;

Wallgren, A ;

Wilhelmsen, L ;

Hellqvist, L ;

Hasselblom, S ;

Carneskog, J ;

Lindqvist, O ;

Hoffman, P ;

Olsson, K ;

Tholen, A ;

Stolt, CM ;

Rindner, A ;

Svensson, R ;

Vaart, J ;

Hansen, S ;

Engqvist, L ;

Lannemyr, O ;

Nilsson, PG ;

Linne, I ;

Lilja, G ;

Tallroth, G ;

Hallgren, J ;

Andersson, B ;

Billstrom, R ;

Persson, S ;

Samuelsson, T ;

Odeberg, H ;

Adriansson, M ;

Tove, H ;

Stobeus, N ;

Habberstad, J ;

End, T ;

Dahlen, M .

ANNALS OF INTERNAL MEDICINE, 1996, 124 (02) :212-+

[5] Efficacy of Melphalan and Prednisone Plus Thalidomide in Patients Older Than 75 Years With Newly Diagnosed Multiple Myeloma: IFM 01/01 Trial [J].

Hulin, Cyrille ;

Facon, Thierry ;

Rodon, Philippe ;

Pegourie, Brigitte ;

Benboubker, Lotfi ;

Doyen, Chantal ;

Dib, Mamoun ;

Guillerm, Gaelle ;

Salles, Bruno ;

Eschard, Jean-Paul ;

Lenain, Pascal ;

Casassus, Philippe ;

Azais, Isabelle ;

Decaux, Olivier ;

Garderet, Laurent ;

Mathiot, Claire ;

Fontan, Jean ;

Lafon, Ingrid ;

Virion, Jean Marc ;

Moreau, Philippe .

JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (22) :3664-3670

[6] Thalidomide-dexamethasone compared with melphalan-prednisolone in elderly patients with multiple myeloma [J].

Ludwig, Heinz ;

Hajek, Roman ;

Tothova, Elena ;

Drach, Johannes ;

Adam, Zdenek ;

Labar, Boris ;

Egyed, Miklos ;

Spicka, Ivan ;

Gisslinger, Heinz ;

Greil, Richard ;

Kuhn, Ingrid ;

Zojer, Niklas ;

Hinke, Axel .

BLOOD, 2009, 113 (15) :3435-3442

[7] Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma [J].

Palumbo, A. ;

Rajkumar, S. V. ;

Dimopoulos, M. A. ;

Richardson, P. G. ;

Miguel, J. San ;

Barlogie, B. ;

Harousseau, J. ;

Zonder, J. A. ;

Cavo, M. ;

Zangari, M. ;

Attal, M. ;

Belch, A. ;

Knop, S. ;

Joshua, D. ;

Sezer, O. ;

Ludwig, H. ;

Vesole, D. ;

Blade, J. ;

Kyle, R. ;

Westin, J. ;

Weber, D. ;

Bringhen, S. ;

Niesvizky, R. ;

Waage, A. ;

von Lilienfeld-Toal, M. ;

Lonial, S. ;

Morgan, G. J. ;

Orlowski, R. Z. ;

Shimizu, K. ;

Anderson, K. C. ;

Boccadoro, M. ;

Durie, B. G. ;

Sonneveld, P. ;

Hussein, M. A. .

LEUKEMIA, 2008, 22 (02) :414-423

[8] Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled-trial [J].

Palumbo, A ;

Bringhen, S ;

Coravito, T ;

Merla, E ;

Capporella, V ;

Callea, V ;

Cangialosi, C ;

Grasso, M ;

Rossini, F ;

Galli, M ;

Catalano, L ;

Zamagni, E ;

Petrucci, MT ;

De Stefano, V ;

Ceccarelli, M ;

Ambrosini, MT ;

Avonto, I ;

Falco, P ;

Ciccone, G ;

Liberati, AM ;

Musto, P ;

Boccadoro, M .

LANCET, 2006, 367 (9513) :825-831

[9] Oral melphalan, prednisone, and thalidomide in elderly patients with multiple myeloma: updated results of a randomized controlled trial [J].

Palumbo, Antonio ;

Bringhen, Sara ;

Liberati, Anna M. ;

Caravita, Tommaso ;

Falcone, Antonietta ;

Callea, Vincenzo ;

Montanaro, Marco ;

Ria, Roberto ;

Capaldi, Antonio ;

Zambello, Renato ;

Benevolo, Giulia ;

Derudas, Daniele ;

Dore, Fausto ;

Cavallo, Federica ;

Gay, Francesca ;

Falco, Patrizia ;

Ciccone, Giovannino ;

Musto, Pellegrino ;

Cavo, Michele ;

Boccadoro, Mario .

BLOOD, 2008, 112 (08) :3107-3114

[10] Multicenter, randomized, double-blind, placebo-controlled study of thalidomide plus dexamethasone compared with dexamethasone as initial therapy for newly diagnosed multiple myeloma [J].

Rajkumar, S. Vincent ;

Rosinol, Laura ;

Hussein, Mohamad ;

Catalano, John ;

Jedrzejczak, Wieslaw ;

Lucy, Lela ;

Olesnyckyj, Marta ;

Yu, Zhinuan ;

Knight, Robert ;

Zeldis, Jerome B. ;

Blade, Joan .

JOURNAL OF CLINICAL ONCOLOGY, 2008, 26 (13) :2171-2177

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