Advertisement
Journal of Clinical Oncology  
Search for:
Limit by:
  Browse by Subject or Issue
Home Search or Browse JCO Subscriptions PDA Services My JCO Customer Service

Originally published as JCO Early Release 10.1200/JCO.2006.10.5460 on August 6 2007

Journal of Clinical Oncology, Vol 25, No 25 (September 1), 2007: pp. 3892-3901
© 2007 American Society of Clinical Oncology.

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Save to my personal folders
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Orlowski, R. Z.
Right arrow Articles by Harousseau, J.-L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Orlowski, R. Z.
Right arrow Articles by Harousseau, J.-L.

Randomized Phase III Study of Pegylated Liposomal Doxorubicin Plus Bortezomib Compared With Bortezomib Alone in Relapsed or Refractory Multiple Myeloma: Combination Therapy Improves Time to Progression

Robert Z. Orlowski, Arnon Nagler, Pieter Sonneveld, Joan Bladé, Roman Hajek, Andrew Spencer, Jesús San Miguel, Tadeusz Robak, Anna Dmoszynska, Noemi Horvath, Ivan Spicka, Heather J. Sutherland, Alexander N. Suvorov, Sen H. Zhuang, Trilok Parekh, Liang Xiu, Zhilong Yuan, Wayne Rackoff, Jean-Luc Harousseau

From the University of North Carolina at Chapel Hill, Chapel Hill, NC; Chaim Sheba Medical Center, Tel Hashomer, Israel; Erasmus MC, Rotterdam, the Netherlands; Hospital Clinic I Provincial, Barcelona, Spain; Interní Hematoonkologická klinika Fakultní Brno, Brno; General Faculty Hospital, Prague, Czech Republic; Alfred Hospital, Melbourne; Institute of Medicine and Veterinary Science, Adelaide, Australia; Hospital Universitario de Salamanca, Centro de Investigación del Cáncer- IBMCC (CSIC-USAL), Spain; Medical University of Lodz, Lodz; Medical University of Lublin, Lublin, Poland; University of British Columbia, Vancouver, Canada; First Republican Clinical Hospital of Udmurtia, Izhevsk, Russia; Johnson & Johnson Pharmaceutical Research & Development LLC, Raritan, NJ; and University Hospital Hotel-Dieu, Nantes, France

Address reprint requests to Robert Z. Orlowski, MD, Department of Medicine, Division of Hematology/Oncology, The University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center, Chapel Hill, NC 27599-7295; e-mail: R_Orlowski{at}med.unc.edu

Purpose: This phase III international study compared the efficacy and safety of a combination of pegylated liposomal doxorubicin (PLD) plus bortezomib with bortezomib monotherapy in patients with relapsed or refractory multiple myeloma.

Patients and Methods: Six hundred forty-six patients were randomly assigned to receive either intravenous bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 of an every 21-days cycle, or the same bortezomib regimen with PLD 30 mg/m2 on day 4.

Results: Median time to progression was increased from 6.5 months for bortezomib to 9.3 months with the PLD + bortezomib combination (P = .000004; hazard ratio, 1.82 [monotherapy v combination therapy]; 95% CI, 1.41 to 2.35). The 15-month survival rate for PLD + bortezomib was 76% compared with 65% for bortezomib alone (P = .03). The complete plus partial response rate was 41% for bortezomib and 44% for PLD + bortezomib, a difference that was not statistically significant. Median duration of response was increased from 7.0 to 10.2 months (P = .0008) with PLD + bortezomib. Grade 3/4 adverse events were more frequent in the combination group (80% v 64%), with safety profiles consistent with the known toxicities of the two agents. An increased incidence in the combination group was seen of grade 3/4 neutropenia, thrombocytopenia, asthenia, fatigue, diarrhea, and hand-foot syndrome.

Conclusion: PLD with bortezomib is superior to bortezomib monotherapy for the treatment of patients with relapsed or refractory multiple myeloma. The combination therapy is associated with a higher incidence of grade 3/4 myelosuppression, constitutional symptoms, and GI and dermatologic toxicities.

published online ahead of print at www.jco.org on August 6, 2007.

Supported by Johnson & Johnson Pharmaceutical Research & Development LLC, and is registered at ClinicalTrials.gov corresponding to NCT00103506. Also supported by the Leukemia & Lymphoma Society (Grant No. 6096-07), the Multiple Myeloma Research Foundation, and the National Cancer Institute (RO1 CA102278; all to R.Z.O.).

Presented in part at the 48th Annual Meeting of the American Society of Hematology, Orlando, FL, December 9-12, 2006.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.




This article has been cited by other articles:


Home page
BloodHome page
Q. Chen, W. Xie, D. J. Kuhn, P. M. Voorhees, A. Lopez-Girona, D. Mendy, L. G. Corral, V. P. Krenitsky, W. Xu, L. Moutouh-de Parseval, et al.
Targeting the p27 E3 ligase SCFSkp2 results in p27- and Skp2-mediated cell-cycle arrest and activation of autophagy
Blood, May 1, 2008; 111(9): 4690 - 4699.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
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]


Home page
BloodHome page
R. A. Kyle and S. V. Rajkumar
Multiple myeloma
Blood, March 15, 2008; 111(6): 2962 - 2972.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
D. J. Kuhn, Q. Chen, P. M. Voorhees, J. S. Strader, K. D. Shenk, C. M. Sun, S. D. Demo, M. K. Bennett, F. W. B. van Leeuwen, A. A. Chanan-Khan, et al.
Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma
Blood, November 1, 2007; 110(9): 3281 - 3290.
[Abstract] [Full Text] [PDF]



About
JCO
 Editorial
Roster
 Advertising
Information
 Librarians &
Institutions
 Rights &
Permissions
 Site Map

Copyright © 2007 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
Terms and Conditions of Use
  HighWire Press HighWire Press™ assists in the publication of JCO Online