Journal ArticleDOI
A phase 2 study of bortezomib in relapsed, refractory myeloma.
Paul G. Richardson,Bart Barlogie,James R. Berenson,Seema Singhal,Sundar Jagannath,D. Irwin,S. Vincent Rajkumar,Gordan Srkalovic,Melissa Alsina,Raymond Alexanian,David S. Siegel,Robert Z. Orlowski,David J. Kuter,Steven Limentani,Stephanie J. Lee,Teru Hideshima,Dixie Lee Esseltine,Michael Kauffman,Julian Adams,David P. Schenkein,Kenneth C. Anderson +20 more
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TLDR
Bortezomib, a member of a new class of anticancer drugs, is active in patients with relapsed multiple myeloma that is refractory to conventional chemotherapy.Abstract:
Background Bortezomib, a boronic acid dipeptide, is a novel proteasome inhibitor that has been shown in preclinical and phase 1 studies to have antimyeloma activity. Methods In this multicenter, open-label, nonrandomized, phase 2 trial, we enrolled 202 patients with relapsed myeloma that was refractory to the therapy they had received most recently. Patients received 1.3 mg of bortezomib per square meter of body-surface area twice weekly for 2 weeks, followed by 1 week without treatment, for up to eight cycles (24 weeks). In patients with a suboptimal response, oral dexamethasone (20 mg daily, on the day of and the day after bortezomib administration) was added to the regimen. The response was evaluated according to the criteria of the European Group for Blood and Marrow Transplantation and confirmed by an independent review committee. Results Of 193 patients who could be evaluated, 92 percent had been treated with three or more of the major classes of agents for myeloma, and in 91 percent, the myeloma wa...read more
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Journal ArticleDOI
International uniform response criteria for multiple myeloma
Brian G.M. Durie,J L Harousseau,Jesús F. San Miguel,J. Bladé,Bart Barlogie,Kenneth C. Anderson,Morie A. Gertz,Meletios A. Dimopoulos,Johan Westin,Pieter Sonneveld,Heinz Ludwig,G. Gahrton,Meral Beksac,John Crowley,Andrew Belch,M. Boccadaro,Ingemar Turesson,Douglas E. Joshua,David H. Vesole,Robert A. Kyle,Raymond Alexanian,Guido Tricot,M. Attal,Giampaolo Merlini,R. L. Powles,Paul G. Richardson,K. Shimizu,Patrizia Tosi,Gareth J. Morgan,S V Rajkumar +29 more
TL;DR: The European Group for Blood and Bone Marrow Transplant/International Bone Marrows Transplant Registry criteria have been expanded, clarified and updated to provide a new comprehensive evaluation system to adequately assess clinical outcomes in myeloma.
Journal ArticleDOI
Bortezomib or high-dose dexamethasone for relapsed multiple myeloma
Paul G. Richardson,Pieter Sonneveld,Michael W. Schuster,D. Irwin,Edward A. Stadtmauer,Thierry Facon,Jean-Luc Harousseau,Dina Ben-Yehuda,Sagar Lonial,Hartmut Goldschmidt,Donna E. Reece,Jesús F. San-Miguel,Joan Bladé,Mario Boccadoro,Jamie Cavenagh,William S. Dalton,Anthony Boral,Dixie Lee Esseltine,Jane B. Porter,David P. Schenkein,Kenneth C. Anderson +20 more
TL;DR: Bortezomib is superior to high-dose dexamethasone for the treatment of patients with multiple myeloma who have had a relapse after one to three previous therapies.
Journal ArticleDOI
Improved survival in multiple myeloma and the impact of novel therapies
Shaji Kumar,S. Vincent Rajkumar,Angela Dispenzieri,Martha Q. Lacy,Suzanne R. Hayman,Francis K. Buadi,Steven R. Zeldenrust,David Dingli,Stephen J. Russell,John A. Lust,Philip R. Greipp,Robert A. Kyle,Morie A. Gertz +12 more
TL;DR: Improved outcome of patients with myeloma in recent years is demonstrated, both in the relapsed setting as well as at diagnosis, both from time of diagnosis and the time of relapse.
Journal ArticleDOI
Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma.
Jesús F. San Miguel,Rudolf Schlag,Nuriet K. Khuageva,Meletios A. Dimopoulos,Ofer Shpilberg,Martin Kropff,Ivan Spicka,Maria Teresa Petrucci,Antonio Palumbo,Olga Samoilova,Anna Dmoszynska,Kudrat Abdulkadyrov,Rik Schots,Bin Jiang,Maria-Victoria Mateos,Kenneth C. Anderson,Dixie Lee Esseltine,Kevin Liu,Andrew Cakana,Helgi van de Velde,Paul G. Richardson +20 more
TL;DR: Bortezomib plus melphalan-prednisone alone in patients with newly diagnosed myeloma who were ineligible for high-dose therapy was superior to melphAlan-predisonsone alone.
Journal ArticleDOI
Targeting apoptosis pathways in cancer therapy.
TL;DR: The current understanding of the apoptotic pathways, including the extrinsic (cytoplasmic) and intrinsic (mitochondrial) pathways, and the agents being developed to target these pathways are reviewed.
References
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Journal ArticleDOI
A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Français du Myélome.
Michel Attal,Jean-Luc Harousseau,Anne-Marie Stoppa,Jean-Jacques Sotto,Jean-Gabriel Fuzibet,Jean-François Rossi,Philippe Casassus,Hervé Maisonneuve,Thierry Facon,Norbert Ifrah,Catherine Payen,Régis Bataille +11 more
TL;DR: The response rate among the patients who received high-dose therapy was 81 percent, whereas it was 57 percent in the group treated with conventional chemotherapy (P<0.001).
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Antitumor activity of thalidomide in refractory multiple myeloma.
Seema Singhal,Jayesh Mehta,Raman Desikan,D Ayers,Paula K. Roberson,Paul Eddlemon,Nikhil C. Munshi,Elias Anaissie,Carla S. Wilson,Madhav V. Dhodapkar,J Zeddis,Bart Barlogie +11 more
TL;DR: Thalidomide can induce marked and durable responses in some patients with multiple myeloma, including those who relapse after high-dose chemotherapy, and is active against advancedMyeloma.
Journal ArticleDOI
Role of the ubiquitin-proteasome pathway in regulating abundance of the cyclin-dependent kinase inhibitor p27
Michele Pagano,Sun W. Tam,Anne M. Theodoras,Peggy Beer-Romero,Giannino Del Sal,Vincent Chau,P. Renee Yew,Giulio Draetta,Mark Rolfe +8 more
TL;DR: Compared with proliferating cells, quiescent cells exhibited a smaller amount of p27 ubiquitinating activity, which accounted for the marked increase of p 27 half-life measured in these cells, indicating that the abundance of p26 in cells is regulated by degradation.
Journal ArticleDOI
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.
Joan Bladé,Diana Samson,Donna E. Reece,Jane F. Apperley,Bo Björkstrand,Gösta Gahrton,Morie A. Gertz,Sergio Giralt,SUNDARr Jagannath,David H. Vesole +9 more
TL;DR: New criteria for response and progression have been developed as a result of discussions between representatives of the Myeloma Subcommittee of the Chronic Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT) and representatives ofThe Myelomas Working Committee of the Autologousblood and marrow transplant Registry (ABMTR) and the International Bone Marrowtransplant Registry (IBMTR).
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