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Blood, 15 April 2005, Vol. 105, No. 8, pp. 3058-3065. Prepublished online as a Blood First Edition Paper on December 30, 2004; DOI 10.1182/blood-2004-07-2911. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-07-2911v1 105/8/3058    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 Orlowski, R. Z. Articles by Dees, E. C. Search for Related Content PubMed PubMed Citation Articles by Orlowski, R. Z. Articles by Dees, E. C. Related Collections Neoplasia Signal Transduction Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Phase 1 trial of the proteasome inhibitor bortezomib and pegylated liposomal doxorubicin in patients with advanced hematologic malignancies Robert Z. Orlowski, Peter M. Voorhees, Reynaldo A. Garcia, Melissa D. Hall, Fred J. Kudrik, Tammy Allred, Anandhi R. Johri, Paul E. Jones, Anastasia Ivanova, Hendrik W. Van Deventer, Don A. Gabriel, Thomas C. Shea, Beverly S. Mitchell, Julian Adams, Dixie-Lee Esseltine, Elizabeth G. Trehu, Marie Green, Mary Jo Lehman, Susan Natoli, Jason M. Collins, Celeste M. Lindley, and E. Claire Dees From The Lineberger Comprehensive Cancer Center, Department of Medicine, Division of Hematology/Oncology, Department of Biostatistics, and School of Pharmacy, all of University of North Carolina at Chapel Hill, Chapel Hill, NC; and Millennium Pharmaceuticals, Cambridge, MA. Proteasome inhibitors, a novel class of chemotherapeutic agents, enhance the antitumor efficacy of anthracyclines in vitro and in vivo. We therefore sought to determine the maximum tolerated dose (MTD) and dose-limiting toxicities of bortezomib and pegylated liposomal doxorubicin (PegLD). Bortezomib was given on days 1, 4, 8, and 11 from 0.90 to 1.50 mg/m2 and PegLD on day 4 at 30 mg/m2 to 42 patients with advanced hematologic malignancies. Grade 3 or 4 toxicities in at least 10% of patients included thrombocytopenia, lymphopenia, neutropenia, fatigue, pneumonia, peripheral neuropathy, febrile neutropenia, and diarrhea. The MTD based on cycle 1 was 1.50 and 30 mg/m2 of bortezomib and PegLD, respectively. However, due to frequent dose reductions and delays at this level, 1.30 and 30 mg/m2 are recommended for further study. Pharmacokinetic and pharmacodynamic studies did not find significant drug interactions between these agents. Antitumor activity was seen against multiple myeloma, with 8 of 22 evaluable patients having a complete response (CR) or near-CR, including several with anthracycline-refractory disease, and another 8 having partial responses (PRs). One patient with relapsed/refractory T-cell non-Hodgkin lymphoma (NHL) achieved a CR, whereas 2 patients each with acute myeloid leukemia and B-cell NHL had PRs. Bortezomib/PegLD was safely administered in this study with promising antitumor activity, supporting further testing of this regimen. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. J. Jakubowiak, T. 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