Assistant Professor
Clinical Research
Hematology-Oncology
Last Updated: 5/24/2010
| Peter Voorhees, M.D.
Assistant Professor | |
Clinical Interests
Hematologic malignancies, with a focus on plasma cell dyscrasias (including, but not limited to, multiple myeloma, solitary plasmacytoma, Waldenstrom's Macroglobulinemia, amyloidosis, monoclonal gammopathy of undetermined significance, Castleman's disease, etc).
Research Interests
My research focuses on better understanding the basis of resistance to chemotherapy in multiple myeloma and the development of therapeutic strategies that overcome chemotherapy resistance. I am also interested in the basis of chemotherapy-related toxicity and the development of tools that predict for adverse events with treatment.
Interleukin-6 (IL-6) is a growth factor present in the bone marrow microenvironment that plays an important role in myeloma cell growth, survival, and resistance to therapy. We have previously shown that treatment of myeloma cell lines and patient myeloma samples with siltuximab, a monoclonal antibody that binds and neutralizes IL-6, accelerates bortezomib-mediated myeloma cell death. We have also demonstrated potent synergy between siltuximab and dexamethasone in preclinical models of myeloma, an effect that was largely due to the ability of siltuximab to interfere with induction of the Ras-MEK-MAPK pathway by IL-6. These studies have paved the way for the development of the following studies for patients with multiple myeloma: 1) CO328T05. A phase II study of siltuximab and dexamethasone in patients with bortezomib pre-treated, relapsed/refractory multiple myeloma; 2) CO328T06. A randomized, phase II study of bortezomib with or without siltuximab in patients with bortezomib-naïve, relapsed/refractory multiple myeloma; and 3) CNTO328 MMY2001. A phase III study of melphalan, prednisone, and bortezomib with or without siltuximab for newly-diagnosed, transplant ineligible patients with multiple myeloma. These studies will further clarify the role of IL-6 targeted therapy for the treatment of myeloma.
Studies have revealed striking synergy between bortezomib and the deacetylase inhibitor vorinostat in preclinical models of multiple myeloma, an effect that is due in part to the ability of vorinostat to interfere with clearance of misfolded/oxidized proteins. Furthermore, additive to synergistic activity has been seen when anthracyclines are combined with vorinostat. Therefore, we have launched a phase I study through the North Carolina Myeloma Study Group evaluating the combination of the anthracycline, Doxil, bortezomib, and vorinostat in patients with relapsed/refractory multiple myeloma. Results from this study will help guide the development of future phase II and III studies of this combination in patients with multiple myeloma.
There has been significant progress made in the understanding of myeloma pathogenesis, and this progress has yielded a large number of new, rationale targets for myeloma therapy. As the era of targeted therapy moves forward, there will be an increasing need for tools that measure the ability of new therapeutics to achieve their desired effect. To this end, in collaboration with Nancy Allbritton and Marcey Waters in the Department of Chemistry, we are developing fluorescent probes that will measure enzyme activity at the single cell level. These probes will serve as useful tools for the evaluation of specific enzyme activities in myeloma pathogenesis, facilitate research into the mechanistic basis of drug resistance to targeted agents, and provide a means of assessing the ability of new drugs to “hit their target” at the level of the myeloma cell.
In collaboration with Drs. Raj Kasthuri, Nigel Key, and Nigel Mackman, we are evaluating the role of tissue factor in venous thromboembolism associated with myeloma therapy, in particular the immunomodulatory drugs, thalidomide and lenalidomide. As a first step, enrollment onto a pilot study measuring tissue factor levels in myeloma patients is on-going.
The ultimate goal of this work is to better tailor therapy to the individual myeloma patient, thus maximizing treatment efficacy while minimizing toxicity.
Training
Georgetown University, Washington, D.C. BA 1998-1992 Biology
Univ. of Michigan Medical School, Ann Arbor, MI MD 1992-1997 Medicine
University of Wisconsin, Madison, WI Residency 1997-2000 Internal Medicine
University of Wisconsin, Madison, WI Chief Residency 2000-2001 Internal Medicine
University of North Carolina at Chapel Hill, NC Fellowship 2001-2004 Hematology-Oncology
Publications
• Uaprasert N, Voorhees PM, Mackman N, Key NS: Venous thromboembolism in multiple myeloma: Current perspectives in pathogenesis. Eur J of Cancer, 201 April 10. [Epub ahead of print]
• Voorhees PM, Chen Q, Small GW, Kuhn DJ, Hunsucker SA, Nemeth JA, Orlowski RZ. Targeted inhibition of interleukin-6 with CNTO 328 sensitizes pre-clinical models of multiple myeloma to dexamethasone-mediated cell death. British Journal of Haematology, 145(4): 315-9, 2009.
• McCudden CR, Voorhees PM, Hammett-Stabler CA. A case of hook effect in the serum free light chain assay using the Olympus AU400e. Clin Biochem, 42(1-2): 121-4, 2009.
• Kuhn DJ, Hunsucker SA, Chen Q, Voorhees PM, Orlowski M, Orlowski RZ. Targeted inhibition of the immunoproteasome is a potent strategy against models of multiple myeloma that overcomes resistance to conventional drugs and non-specific proteasome inhibitors. Blood, 113(19): 4667-76, 2009.
• Jones RJ, Chen Q, Voorhees PM, Young KH, Bruey-Sedano N, Yang D, Orlowski RZ. Inhibition of the p53 E3 ligase HDM-2 induces apoptosis and DNA damage--independent p53 phosphorylation in mantle cell lymphoma. Clinical Cancer Research, 14(17): 5416-25, 2008.
• Chang J, Voorhees P, Kolesar J, Ahuja H, Sanchez F, Rodriguez G, Kim K, Werndli J, Bailey H, Kahl B. Phase II study of arsenic trioxide and ascorbic acid for relapsed or refractory lymphoid malignancies: a Wisconsin Oncology Network study. Hematology Oncology, 27(1): 11-6, 2009.
• Chen Q, Xie W, Kuhn DJ, Voorhees PM, Lopez-Girona A, Mendy D, Corral LG, Krenitsky VP, Xu W, Moutouh-de Parseval L, Webb DR, Mercurio F, Nakayama KI, Nakayama K, Orlowski RZ. Targeting the p27 E3 ligase SCFSkp2 results in p27- and Skp2-mediated cell cycle arrest, and activation of autophagy. Blood, 111(9): 4690-9, 2008.
• Voorhees PM, Chen Q, Kuhn DJ, Small GW, Hunsucker SA, Strader JS, Corringham RE, Zaki MH, Nemeth JA, Orlowski RZ. Inhibition of interleukin-6 signaling with CNTO 328 enhances the activity of bortezomib in pre-clinical models of multiple myeloma. Clinical Cancer Research, 13(21): 6469-6478, 2007.
• Kuhn DJ, Chen Q, Voorhees PM, Strader JS, Shenk KD, Sun CM, Demo SD, Bennett MK, van Leeuwen FW, Chanan-Khan AA, Orlowski RZ. Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against pre-clinical models of multiple myeloma. Blood, 110(9): 3281-90, 2007.
• Voorhees PM and Orlowski RZ: Emerging data on the use of anthracyclines in combination with bortezomib in multiple myeloma. Clin Lymphoma Myeloma, 7(Suppl. 4): S156-62, 2007.
• Biehn SE, Moore DT, Voorhees PM, Garcia RA, Lehman MJ, Dees EC, Orlowski RZ. Extended follow-up of outcome measures in multiple myeloma patients treated on a phase I study with bortezomib and pegylated liposomal doxorubicin. Ann Hematol,. 86(3): 211-6, 2007.
• Voorhees PM and Orlowski RZ: The Emerging Role of Novel Combinations for Induction Therapy in Multiple Myeloma. Clin Lymphoma Myeloma, 7(1): 33-41, 2006.
• Orlowski RZ, Voorhees PM, Garcia RA, Hall MD, Kudrik FJ, Allred T, Johri AR, Jones PE, Ivanova A, Van Deventer HW, Gabriel DA, Shea TC, Mitchell BS, Adams J, Esseltine DL, Trehu EG, Green M, Lehman MJ, Natoli S, Collins JM, Lindley CM, Dees EC: Phase I trial of the proteasome inhibitor bortezomib and pegylated liposomal doxorubicin in patients with advanced hematologic malignancies. Blood, 105(8): 3058-65, 2005.
• Voorhees PM, Carder KA, Smith SV, Ayscue LH, Rao KW, Dunphy CH: Follicular lymphoma with a Burkitt’s translocation: Predictor of an aggressive clinical course. Case report and review of the literature. The Archives of Pathology and Laboratory Medicine, 128(2):210-3, 2004.
• Voorhees PM, Dees EC, O’ Neil B, Orlowski RZ: The proteasome as a target for cancer therapy. Clinical Cancer Research, 9:6316-6325, 2003.
E-mail: Peter_voorhees@med.unc.edu
Telephone: 966-4431
FAX: 966-6735
Address: UNC School of Medicine, Physicians Office Building, 170 Manning Drive, Campus Box #7305 Chapel Hill, NC 27599-7305