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Annals of Oncology Advance Access published online on May 25, 2008
Annals of Oncology, doi:10.1093/annonc/mdn365
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© The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Bortezomib and gemcitabine in relapsed or refractory Hodgkin's lymphoma

J. H. Mendler, J. Kelly, S. Voci, D. Marquis, L. Rich, R. M. Rossi, S. H. Bernstein, C. T. Jordan, J. Liesveld, R. I. Fisher and J. W. Friedberg*

Department of Internal Medicine, James P. Wilmot Cancer Center, University of Rochester Medical Center, Rochester, USA

* Correspondence to: J. W. Friedberg, MD, Associate Professor of Medicine and Oncology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 704, Rochester, NY 14642, USA. Tel: +1-585-273-4150; Fax: +1-585-276-0337; E-mail: jonathan_friedberg{at}urmc.rochester.edu

Background: Given the significant activity and tolerability of gemcitabine in patients with relapsed Hodgkin's lymphoma (HL), the critical role that nuclear factor kappa B (NF-{kappa}B) appears to play in the pathogenesis of this tumor, the ability of bortezomib to inhibit NF-{kappa}B activity, and laboratory studies suggesting synergistic antitumor effects of gemcitabine and bortezomib, we hypothesized that this combination would be efficacious in patients with relapsed or refractory HL.

Patients and methods: A total of 18 patients participated. Patients received 3-week cycles of bortezomib 1 mg/m2 on days 1, 4, 8, and 11 plus gemcitabine 800 mg/m2 on days 1 and 8.

Results: The overall response rate for all patients was 22% (95% confidence interval 3% to 42%). Three patients developed grade III transaminase elevation: one was removed from the study and two had doses of gemcitabine held. Almost all patients exhibited inhibition of proteasome activity with treatment.

Conclusions: The combination of gemcitabine and bortezomib is a less active and more toxic regimen in relapsed HL than other currently available treatments. It poses a risk of severe liver toxicity and should be pursued with caution in other types of cancer.

bortezomib, gemcitabine, hepatotoxicity, Hodgkin's lymphoma, proteasome, relapsed

Received for publication January 18, 2008. Revision received April 8, 2008. Accepted for publication April 23, 2008.


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