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Blood, 1 December 2005, Vol. 106, No. 12, pp. 3777-3784. Prepublished online as a Blood First Edition Paper on August 11, 2005; DOI 10.1182/blood-2005-03-1173. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-03-1173v1 106/12/3777    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lonial, S. Articles by Anderson, K. C. Search for Related Content PubMed PubMed Citation Articles by Lonial, S. Articles by Anderson, K. C. Related Collections Hemostasis, Thrombosis, and Vascular Biology Neoplasia Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS Risk factors and kinetics of thrombocytopenia associated with bortezomib for relapsed, refractory multiple myeloma Sagar Lonial, Edmund K. Waller, Paul G. Richardson, Sundar Jagannath, Robert Z. Orlowski, Cynthia R. Giver, David L. Jaye, Dixil Francis, Sara Giusti, Claire Torre, Bart Barlogie, James R. Berenson, Seema Singhal, David P. Schenkein, Dixie-Lee W. Esseltine, Jessica Anderson, Hugh Xiao, Leonard T. Heffner, Kenneth C. Anderson, for the SUMMIT/CREST Investigators From the Winship Cancer Institute, Emory University, Atlanta, GA; Dana Farber Cancer Institute, Boston, MA; St Vincent's Comprehensive Cancer Center, New York, NY; University of North Carolina at Chapel Hill; Myeloma and Transplant Research Center, Arkansas Cancer Research Center, Little Rock; Institute for Myeloma and Bone Cancer Research, West Hollywood, CA; Northwestern University, Chicago, IL; and Millennium Pharmaceuticals, Cambridge, MA. Bortezomib, a proteasome inhibitor with efficacy in multiple myeloma, is associated with thrombocytopenia, the cause and kinetics of which are different from those of standard cytotoxic agents. We assessed the frequency, kinetics, and mechanism of thrombocytopenia following treatment with bortezomib 1.3 mg/m2 in 228 patients with relapsed and/or refractory myeloma in 2 phase 2 trials. The mean platelet count decreased by approximately 60% during treatment but recovered rapidly between treatments in a cyclic fashion. Among responders, the pretreatment platelet count increased significantly during subsequent cycles of therapy. The mean percent reduction in platelets was independent of baseline platelet count, M-protein concentration, and marrow plasmacytosis. Plasma thrombopoietin levels inversely correlated with platelet count. Murine studies demonstrated a reduction in peripheral platelet count following a single bortezomib dose without negative effects on megakaryocytic cellularity, ploidy, or morphology. These data suggest that bortezomib-induced thrombocytopenia is due to a reversible effect on megakaryocytic function rather than a direct cytotoxic effect on megakaryocytes or their progenitors. The exact mechanism underlying bortezomib-induced thrombocytopenia remains unknown but it is unlikely to be related to marrow injury or decreased thrombopoietin production. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. R. Berenson, O. Yellin, R. Patel, H. Duvivier, Y. Nassir, R. Mapes, C. D. Abaya, and R. A. Swift A Phase I Study of Samarium Lexidronam/Bortezomib Combination Therapy for the Treatment of Relapsed or Refractory Multiple Myeloma Clin. Cancer Res., February 1, 2009; 15(3): 1069 - 1075. [Abstract] [Full Text] [PDF] K. N. Utecht and J. Kolesar Bortezomib: A novel chemotherapeutic agent for hematologic malignancies Am. J. Health Syst. Pharm., July 1, 2008; 65(13): 1221 - 1231. [Abstract] [Full Text] [PDF] M. Zangari, J. Guerrero, F. Cavallo, H. K. Prasad, D. Esseltine, and L. Fink Hemostatic effects of bortezomib treatment in patients with relapsed or refractory multiple myeloma Haematologica, June 1, 2008; 93(6): 953 - 954. [Full Text] [PDF] R. Z. Orlowski and D. J. Kuhn Proteasome Inhibitors in Cancer Therapy: Lessons from the First Decade Clin. Cancer Res., March 15, 2008; 14(6): 1649 - 1657. [Abstract] [Full Text] [PDF] D. Chauhan, A. Singh, M. Brahmandam, K. Podar, T. Hideshima, P. Richardson, N. Munshi, M. A. Palladino, and K. C. Anderson Combination of proteasome inhibitors bortezomib and NPI-0052 trigger in vivo synergistic cytotoxicity in multiple myeloma Blood, February 1, 2008; 111(3): 1654 - 1664. [Abstract] [Full Text] [PDF] P. G. Richardson, P. Sonneveld, M. Schuster, D. Irwin, E. Stadtmauer, T. Facon, J.-L. Harousseau, D. Ben-Yehuda, S. Lonial, H. Goldschmidt, et al. Extended follow-up of a phase 3 trial in relapsed multiple myeloma: final time-to-event results of the APEX trial Blood, November 15, 2007; 110(10): 3557 - 3560. [Abstract] [Full Text] [PDF] R. Manochakian, K. C. Miller, and A. A. Chanan-Khan Clinical Impact of Bortezomib in Frontline Regimens for Patients with Multiple Myeloma Oncologist, August 1, 2007; 12(8): 978 - 990. [Abstract] [Full Text] [PDF] S. D. Demo, C. J. Kirk, M. A. Aujay, T. J. Buchholz, M. Dajee, M. N. Ho, J. Jiang, G. J. Laidig, E. R. Lewis, F. Parlati, et al. Antitumor Activity of PR-171, a Novel Irreversible Inhibitor of the Proteasome Cancer Res., July 1, 2007; 67(13): 6383 - 6391. [Abstract] [Full Text] [PDF] O. Wagner-Ballon, D. F. Pisani, T. Gastinne, M. Tulliez, R. Chaligne, C. Lacout, F. Aurade, J.-L. Villeval, P. Gonin, W. Vainchenker, et al. Proteasome inhibitor bortezomib impairs both myelofibrosis and osteosclerosis induced by high thrombopoietin levels in mice Blood, July 1, 2007; 110(1): 345 - 353. [Abstract] [Full Text] [PDF] J. Voortman, E. F. Smit, R. Honeywell, B. C. Kuenen, G. J. Peters, H. van de Velde, and G. Giaccone A Parallel Dose-Escalation Study of Weekly and Twice-Weekly Bortezomib in Combination with Gemcitabine and Cisplatin in the First-Line Treatment of Patients with Advanced Solid Tumors Clin. Cancer Res., June 15, 2007; 13(12): 3642 - 3651. [Abstract] [Full Text] [PDF] P. G. Richardson, C. Mitsiades, R. Schlossman, N. Munshi, and K. Anderson New Drugs for Myeloma Oncologist, June 1, 2007; 12(6): 664 - 689. [Abstract] [Full Text] [PDF] R. I. Fisher, S. H. Bernstein, B. S. Kahl, B. Djulbegovic, M. J. Robertson, S. de Vos, E. Epner, A. Krishnan, J. P. Leonard, S. Lonial, et al. Multicenter Phase II Study of Bortezomib in Patients With Relapsed or Refractory Mantle Cell Lymphoma J. Clin. Oncol., October 20, 2006; 24(30): 4867 - 4874. [Abstract] [Full Text] [PDF] P. G. Richardson, H. Briemberg, S. Jagannath, P. Y. Wen, B. Barlogie, J. Berenson, S. Singhal, D. S. Siegel, D. Irwin, M. Schuster, et al. Frequency, Characteristics, and Reversibility of Peripheral Neuropathy During Treatment of Advanced Multiple Myeloma With Bortezomib J. Clin. Oncol., July 1, 2006; 24(19): 3113 - 3120. [Abstract] [Full Text] [PDF]

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