A Phase 2 Study of Bortezomib in Relapsed, Refractory Myeloma
Paul G. Richardson, M.D., Bart Barlogie, M.D., Ph.D., James Berenson, M.D., Seema Singhal, M.D., Sundar Jagannath, M.D., David Irwin, M.D., S. Vincent Rajkumar, M.D., Gordan Srkalovic, M.D., Melissa Alsina, M.D., Raymond Alexanian, M.D., David Siegel, M.D., Robert Z. Orlowski, M.D., David Kuter, M.D., Ph.D., Steven A. Limentani, M.D., Stephanie Lee, M.D., Teru Hideshima, M.D., Ph.D., Dixie-Lee Esseltine, M.D., Michael Kauffman, M.D., Ph.D., Julian Adams, Ph.D., David P. Schenkein, M.D., and Kenneth C. Anderson, M.D.
Background Bortezomib, a boronic acid dipeptide, is a novelproteasome inhibitor that has been shown in preclinical andphase 1 studies to have antimyeloma activity.
Methods In this multicenter, open-label, nonrandomized, phase2 trial, we enrolled 202 patients with relapsed myeloma thatwas refractory to the therapy they had received most recently.Patients received 1.3 mg of bortezomib per square meter of body-surfacearea twice weekly for 2 weeks, followed by 1 week without treatment,for up to eight cycles (24 weeks). In patients with a suboptimalresponse, oral dexamethasone (20 mg daily, on the day of andthe day after bortezomib administration) was added to the regimen.The response was evaluated according to the criteria of theEuropean Group for Blood and Marrow Transplantation and confirmedby an independent review committee.
Results Of 193 patients who could be evaluated, 92 percent hadbeen treated with three or more of the major classes of agentsfor myeloma, and in 91 percent, the myeloma was refractory tothe therapy received most recently. The rate of response tobortezomib was 35 percent, and those with a response included7 patients in whom myeloma protein became undetectable and 12in whom myeloma protein was detectable only by immunofixation.The median overall survival was 16 months, with a median durationof response of 12 months. Grade 3 adverse events included thrombocytopenia(in 28 percent of patients), fatigue (in 12 percent), peripheralneuropathy (in 12 percent), and neutropenia (in 11 percent).Grade 4 events occurred in 14 percent of patients.
Conclusions Bortezomib, a member of a new class of anticancerdrugs, is active in patients with relapsed multiple myelomathat is refractory to conventional chemotherapy.
Source Information
From the Dana–Farber Cancer Institute, Boston (P.G.R., S.L., T.H., K.C.A.); University of Arkansas, Little Rock (B.B.); Cedars–Sinai Medical Center, Los Angeles (J.B.); Northwestern University Medical Center, Chicago (S.S.); St. Vincent's Catholic Medical Center, New York (S.J.); Alta Bates Cancer Center, Berkeley, Calif. (D.I.); Mayo Clinic, Rochester, Minn. (S.V.R.); Cleveland Clinic Foundation, Cleveland (G.S.); H. Lee Moffitt Cancer Center, Tampa, Fla. (M.A.); M.D. Anderson Cancer Center, Houston (R.A.); Carol G. Simon Cancer Center, Morristown, N.J. (D.S.); University of North Carolina, Chapel Hill (R.Z.O.); Massachusetts General Hospital, Boston (D.K.); Charlotte Medical Clinic, Charlotte, N.C. (S.A.L.); and Millennium Pharmaceuticals, Cambridge, Mass. (D.-L.E., M.K., J.A., D.P.S.).
Address reprint requests to Dr. Richardson at the Department of Adult Oncology, Dana–Farber Cancer Institute, 44 Binney St., Dana 1B12, Boston, MA 02115, or at paul_richardson{at}dfci.harvard.edu.
Richardson, P. G., Weller, E., Jagannath, S., Avigan, D. E., Alsina, M., Schlossman, R. L., Mazumder, A., Munshi, N. C., Ghobrial, I. M., Doss, D., Warren, D. L., Lunde, L. E., McKenney, M., Delaney, C., Mitsiades, C. S., Hideshima, T., Dalton, W., Knight, R., Esseltine, D.-L., Anderson, K. C.
(2009). Multicenter, Phase I, Dose-Escalation Trial of Lenalidomide Plus Bortezomib for Relapsed and Relapsed/Refractory Multiple Myeloma. JCO
27: 5713-5719
[Abstract][Full Text]
Harousseau, J.-L., Avet-Loiseau, H., Attal, M., Charbonnel, C., Garban, F., Hulin, C., Michallet, M., Facon, T., Garderet, L., Marit, G., Ketterer, N., Lamy, T., Voillat, L., Guilhot, F., Doyen, C., Mathiot, C., Moreau, P.
(2009). Achievement of at Least Very Good Partial Response Is a Simple and Robust Prognostic Factor in Patients With Multiple Myeloma Treated With High-Dose Therapy: Long-Term Analysis of the IFM 99-02 and 99-04 Trials. JCO
27: 5720-5726
[Abstract][Full Text]
Ooi, M. G., Hayden, P. J., Kotoula, V., McMillin, D. W., Charalambous, E., Daskalaki, E., Raje, N. S., Munshi, N. C., Chauhan, D., Hideshima, T., Buon, L., Clynes, M., O'Gorman, P., Richardson, P. G., Mitsiades, C. S., Anderson, K. C., Mitsiades, N.
(2009). Interactions of the Hdm2/p53 and Proteasome Pathways May Enhance the Antitumor Activity of Bortezomib. Clin. Cancer Res.
15: 7153-7160
[Abstract][Full Text]
Lacy, M. Q., Hayman, S. R., Gertz, M. A., Dispenzieri, A., Buadi, F., Kumar, S., Greipp, P. R., Lust, J. A., Russell, S. J., Dingli, D., Kyle, R. A., Fonseca, R., Bergsagel, P. L., Roy, V., Mikhael, J. R., Stewart, A. K., Laumann, K., Allred, J. B., Mandrekar, S. J., Rajkumar, S. V.
(2009). Pomalidomide (CC4047) Plus Low-Dose Dexamethasone As Therapy for Relapsed Multiple Myeloma. JCO
27: 5008-5014
[Abstract][Full Text]
Jakubowiak, A. J., Kendall, T., Al-Zoubi, A., Khaled, Y., Mineishi, S., Ahmed, A., Campagnaro, E., Brozo, C., Braun, T., Talpaz, M., Kaminski, M. S.
(2009). Phase II Trial of Combination Therapy With Bortezomib, Pegylated Liposomal Doxorubicin, and Dexamethasone in Patients With Newly Diagnosed Myeloma. JCO
27: 5015-5022
[Abstract][Full Text]
de Vos, S., Goy, A., Dakhil, S. R., Saleh, M. N., McLaughlin, P., Belt, R., Flowers, C. R., Knapp, M., Hart, L., Patel-Donnelly, D., Glenn, M., Gregory, S. A., Holladay, C., Zhang, T., Boral, A. L.
(2009). Multicenter Randomized Phase II Study of Weekly or Twice-Weekly Bortezomib Plus Rituximab in Patients With Relapsed or Refractory Follicular or Marginal-Zone B-Cell Lymphoma. JCO
27: 5023-5030
[Abstract][Full Text]
Kager, L. M, Kersten, M.-J., Kloppenborg, R. P., Van Oers, R., Van den Born, B.-J.
(2009). Reversible posterior leucoencephalopathy syndrome associated with bortezomib in a patient with relapsed multiple myeloma. BMJ Case Reports
2009: bcr0620091926-bcr0620091926
[Abstract][Full Text]
Blotta, S., Tassone, P., Prabhala, R. H., Tagliaferri, P., Cervi, D., Amin, S., Jakubikova, J., Tai, Y.-T., Podar, K., Mitsiades, C. S., Zullo, A., Franco, B., Anderson, K. C., Munshi, N. C.
(2009). Identification of novel antigens with induced immune response in monoclonal gammopathy of undetermined significance. Blood
114: 3276-3284
[Abstract][Full Text]
Harousseau, J.-L., Attal, M., Avet-Loiseau, H.
(2009). The role of complete response in multiple myeloma. Blood
114: 3139-3146
[Abstract][Full Text]
Anguiano, A., Tuchman, S. A., Acharya, C., Salter, K., Gasparetto, C., Zhan, F., Dhodapkar, M., Nevins, J., Barlogie, B., Shaughnessy, J. D. Jr, Potti, A.
(2009). Gene Expression Profiles of Tumor Biology Provide a Novel Approach to Prognosis and May Guide the Selection of Therapeutic Targets in Multiple Myeloma. JCO
27: 4197-4203
[Abstract][Full Text]
Reece, D. E., Sanchorawala, V., Hegenbart, U., Merlini, G., Palladini, G., Fermand, J.-P., Vescio, R. A., Liu, X., Elsayed, Y. A., Cakana, A., Comenzo, R. L., for the VELCADE CAN2007 Study Group,
(2009). Weekly and twice-weekly bortezomib in patients with systemic AL amyloidosis: results of a phase 1 dose-escalation study. Blood
114: 1489-1497
[Abstract][Full Text]
Badros, A., Burger, A. M., Philip, S., Niesvizky, R., Kolla, S. S., Goloubeva, O., Harris, C., Zwiebel, J., Wright, J. J., Espinoza-Delgado, I., Baer, M. R., Holleran, J. L., Egorin, M. J., Grant, S.
(2009). Phase I Study of Vorinostat in Combination with Bortezomib for Relapsed and Refractory Multiple Myeloma. Clin. Cancer Res.
15: 5250-5257
[Abstract][Full Text]
Treon, S. P., Ioakimidis, L., Soumerai, J. D., Patterson, C. J., Sheehy, P., Nelson, M., Willen, M., Matous, J., Mattern, J. II, Diener, J. G., Keogh, G. P., Myers, T. J., Boral, A., Birner, A., Esseltine, D. L., Ghobrial, I. M.
(2009). Primary Therapy of Waldenstrom Macroglobulinemia With Bortezomib, Dexamethasone, and Rituximab: WMCTG Clinical Trial 05-180. JCO
27: 3830-3835
[Abstract][Full Text]
Huber, J. M., Tagwerker, A., Heininger, D., Mayer, G., Rosenkranz, A. R., Eller, K.
(2009). The proteasome inhibitor Bortezomib aggravates renal ischemia-reperfusion injury. Am. J. Physiol. Renal Physiol.
297: F451-F460
[Abstract][Full Text]
Hu, Y., Kirito, K., Yoshida, K., Mitsumori, T., Nakajima, K., Nozaki, Y., Hamanaka, S., Nagashima, T., Kunitama, M., Sakoe, K., Komatsu, N.
(2009). Inhibition of hypoxia-inducible factor-1 function enhances the sensitivity of multiple myeloma cells to melphalan. Molecular Cancer Therapeutics
8: 2329-2338
[Abstract][Full Text]
McConkey, D. J.
(2009). Bortezomib paradigm shift in myeloma. Blood
114: 931-932
[Abstract][Full Text]
Hideshima, T., Ikeda, H., Chauhan, D., Okawa, Y., Raje, N., Podar, K., Mitsiades, C., Munshi, N. C., Richardson, P. G., Carrasco, R. D., Anderson, K. C.
(2009). Bortezomib induces canonical nuclear factor-{kappa}B activation in multiple myeloma cells. Blood
114: 1046-1052
[Abstract][Full Text]
Richardson, P., Jagannath, S., Hussein, M., Berenson, J., Singhal, S., Irwin, D., Williams, S. F., Bensinger, W., Badros, A. Z., Vescio, R., Kenvin, L., Yu, Z., Olesnyckyj, M., Zeldis, J., Knight, R., Anderson, K. C.
(2009). Safety and efficacy of single-agent lenalidomide in patients with relapsed and refractory multiple myeloma. Blood
114: 772-778
[Abstract][Full Text]
Richardson, P. G., Xie, W., Mitsiades, C., Chanan-Khan, A. A., Lonial, S., Hassoun, H., Avigan, D. E., Oaklander, A. L., Kuter, D. J., Wen, P. Y., Kesari, S., Briemberg, H. R., Schlossman, R. L., Munshi, N. C., Heffner, L. T., Doss, D., Esseltine, D.-L., Weller, E., Anderson, K. C., Amato, A. A.
(2009). Single-Agent Bortezomib in Previously Untreated Multiple Myeloma: Efficacy, Characterization of Peripheral Neuropathy, and Molecular Correlations With Response and Neuropathy. JCO
27: 3518-3525
[Abstract][Full Text]
Eom, H.-S., Min, C.-K., Cho, B.-S., Lee, S., Lee, J.-W., Min, W.-S., Kim, C.-C., Kim, M., Kim, Y.
(2009). Retrospective Comparison of Bortezomib-containing Regimens with Vincristine-Doxorubicin-Dexamethasone (VAD) as Induction Treatment Prior to Autologous Stem Cell Transplantation for Multiple Myeloma. Jpn J Clin Oncol
39: 449-455
[Abstract][Full Text]
Hoang, B., Benavides, A., Shi, Y., Frost, P., Lichtenstein, A.
(2009). Effect of autophagy on multiple myeloma cell viability. Molecular Cancer Therapeutics
8: 1974-1984
[Abstract][Full Text]
Roccaro, A. M., Sacco, A., Thompson, B., Leleu, X., Azab, A. K., Azab, F., Runnels, J., Jia, X., Ngo, H. T., Melhem, M. R., Lin, C. P., Ribatti, D., Rollins, B. J., Witzig, T. E., Anderson, K. C., Ghobrial, I. M.
(2009). MicroRNAs 15a and 16 regulate tumor proliferation in multiple myeloma. Blood
113: 6669-6680
[Abstract][Full Text]
Soucy, T. A., Smith, P. G., Rolfe, M.
(2009). Targeting NEDD8-Activated Cullin-RING Ligases for the Treatment of Cancer. Clin. Cancer Res.
15: 3912-3916
[Abstract][Full Text]
Henry, L, Lavabre-Bertrand, T, Vercambre, L, Ramos, J, Carillo, S, Guiraud, I, Pouderoux, P, Bismuth, M, Valats, J-C, Demattei, C, Duny, Y, Chaze, I, Funakoshi, N, Bureau, J P, Daures, J-P, Blanc, P
(2009). Plasma proteasome level is a reliable early marker of malignant transformation of liver cirrhosis. Gut
58: 833-838
[Abstract][Full Text]
Hideshima, T., Chauhan, D., Kiziltepe, T., Ikeda, H., Okawa, Y., Podar, K., Raje, N., Protopopov, A., Munshi, N. C., Richardson, P. G., Carrasco, R. D., Anderson, K. C.
(2009). Biologic sequelae of I{kappa}B kinase (IKK) inhibition in multiple myeloma: therapeutic implications. Blood
113: 5228-5236
[Abstract][Full Text]
Kuhn, D. J., Hunsucker, S. A., Chen, Q., Voorhees, P. M., Orlowski, M., Orlowski, R. Z.
(2009). Targeted inhibition of the immunoproteasome is a potent strategy against models of multiple myeloma that overcomes resistance to conventional drugs and nonspecific proteasome inhibitors. Blood
113: 4667-4676
[Abstract][Full Text]
Chanan-Khan, A. A., Sonneveld, P., Harousseau, J.-L., Richardson, P. G.
(2009). Reply to C.A. Dasanu et al. JCO
27: 2294-2296
[Full Text]
Delmonte, A., Ghielmini, M., Sessa, C.
(2009). Beyond Monoclonal Antibodies: New Therapeutic Agents in Non-Hodgkin's Lymphomas. The Oncologist
14: 511-525
[Abstract][Full Text]
Azab, A. K., Runnels, J. M., Pitsillides, C., Moreau, A.-S., Azab, F., Leleu, X., Jia, X., Wright, R., Ospina, B., Carlson, A. L., Alt, C., Burwick, N., Roccaro, A. M., Ngo, H. T., Farag, M., Melhem, M. R., Sacco, A., Munshi, N. C., Hideshima, T., Rollins, B. J., Anderson, K. C., Kung, A. L., Lin, C. P., Ghobrial, I. M.
(2009). CXCR4 inhibitor AMD3100 disrupts the interaction of multiple myeloma cells with the bone marrow microenvironment and enhances their sensitivity to therapy. Blood
113: 4341-4351
[Abstract][Full Text]
Braggio, E., Keats, J. J., Leleu, X., Van Wier, S., Jimenez-Zepeda, V. H., Valdez, R., Schop, R. F.J., Price-Troska, T., Henderson, K., Sacco, A., Azab, F., Greipp, P., Gertz, M., Hayman, S., Rajkumar, S. V., Carpten, J., Chesi, M., Barrett, M., Stewart, A. K., Dogan, A., Bergsagel, P. L., Ghobrial, I. M., Fonseca, R.
(2009). Identification of Copy Number Abnormalities and Inactivating Mutations in Two Negative Regulators of Nuclear Factor-{kappa}B Signaling Pathways in Waldenstrom's Macroglobulinemia. Cancer Res.
69: 3579-3588
[Abstract][Full Text]
Moore, H. E., Davenport, E. L., Smith, E. M., Muralikrishnan, S., Dunlop, A. S., Walker, B. A., Krige, D., Drummond, A. H., Hooftman, L., Morgan, G. J., Davies, F. E.
(2009). Aminopeptidase inhibition as a targeted treatment strategy in myeloma. Molecular Cancer Therapeutics
8: 762-770
[Abstract][Full Text]
Jandial, D. D., Farshchi-Heydari, S., Larson, C. A., Elliott, G. I., Wrasidlo, W. J., Howell, S. B.
(2009). Enhanced Delivery of Cisplatin to Intraperitoneal Ovarian Carcinomas Mediated by the Effects of Bortezomib on the Human Copper Transporter 1. Clin. Cancer Res.
15: 553-560
[Abstract][Full Text]
Dawson, M. A., Opat, S. S., Taouk, Y., Donovan, M., Zammit, M., Monaghan, K., Horvath, N., Roberts, A. W., Prince, H. M., Hertzberg, M., McLean, C. A., Spencer, A.
(2009). Clinical and Immunohistochemical Features Associated with a Response to Bortezomib in Patients with Multiple Myeloma. Clin. Cancer Res.
15: 714-722
[Abstract][Full Text]
Pinzone, J. J., Hall, B. M., Thudi, N. K., Vonau, M., Qiang, Y.-W., Rosol, T. J., Shaughnessy, J. D. Jr
(2009). The role of Dickkopf-1 in bone development, homeostasis, and disease. Blood
113: 517-525
[Abstract][Full Text]
GUAN, M., ZHU, L., SOMLO, G., HUGHES, A., ZHOU, B., YEN, Y.
(2009). Bortezomib Therapeutic Effect is Associated with Expression of FGFR3 in Multiple Myeloma Cells. Anticancer Res
29: 1-9
[Abstract][Full Text]
Lahuerta, J. J., Mateos, M. V., Martinez-Lopez, J., Rosinol, L., Sureda, A., de la Rubia, J., Garcia-Larana, J., Martinez-Martinez, R., Hernandez-Garcia, M. T., Carrera, D., Besalduch, J., de Arriba, F., Ribera, J. M., Escoda, L., Hernandez-Ruiz, B., Garcia-Frade, J., Rivas-Gonzalez, C., Alegre, A., Blade, J., San Miguel, J. F.
(2008). Influence of Pre- and Post-Transplantation Responses on Outcome of Patients With Multiple Myeloma: Sequential Improvement of Response and Achievement of Complete Response Are Associated With Longer Survival. JCO
26: 5775-5782
[Abstract][Full Text]
Narimatsu, H., Hori, A., Matsumura, T., Kodama, Y., Takita, M., Kishi, Y., Hamaki, T., Yuji, K., Tanaka, Y., Komatsu, T., Kami, M.
(2008). Cooperative Relationship Between Pharmaceutical Companies, Academia, and Media Explains Sharp Decrease in Frequency of Pulmonary Complications After Bortezomib in Japan. JCO
26: 5820-5823
[Full Text]
Moreau, P., Coiteux, V., Hulin, C., Leleu, X., van de Velde, H., Acharya, M., Harousseau, J.-L.
(2008). Prospective comparison of subcutaneous versus intravenous administration of bortezomib in patients with multiple myeloma. haematol
93: 1908-1911
[Abstract][Full Text]
Paiva, B., Vidriales, M.-B., Cervero, J., Mateo, G., Perez, J. J., Montalban, M. A., Sureda, A., Montejano, L., Gutierrez, N. C., de Coca, A. G., de las Heras, N., Mateos, M. V., Lopez-Berges, M. C., Garcia-Boyero, R., Galende, J., Hernandez, J., Palomera, L., Carrera, D., Martinez, R., de la Rubia, J., Martin, A., Blade, J., Lahuerta, J. J., Orfao, A., San Miguel, J. F., on behalf of the GEM (Grupo Espanol de MM)/PETHEMA,
(2008). Multiparameter flow cytometric remission is the most relevant prognostic factor for multiple myeloma patients who undergo autologous stem cell transplantation. Blood
112: 4017-4023
[Abstract][Full Text]
Palumbo, A., Bringhen, S., Liberati, A. M., Caravita, T., Falcone, A., Callea, V., Montanaro, M., Ria, R., Capaldi, A., Zambello, R., Benevolo, G., Derudas, D., Dore, F., Cavallo, F., Gay, F., Falco, P., Ciccone, G., Musto, P., Cavo, M., Boccadoro, M.
(2008). Oral melphalan, prednisone, and thalidomide in elderly patients with multiple myeloma: updated results of a randomized controlled trial. Blood
112: 3107-3114
[Abstract][Full Text]
Reece, D. E., Rodriguez, G. P., Chen, C., Trudel, S., Kukreti, V., Mikhael, J., Pantoja, M., Xu, W., Stewart, A. K.
(2008). Phase I-II Trial of Bortezomib Plus Oral Cyclophosphamide and Prednisone in Relapsed and Refractory Multiple Myeloma. JCO
26: 4777-4783
[Abstract][Full Text]
Chanan-Khan, A., Sonneveld, P., Schuster, M. W., Stadtmauer, E. A., Facon, T., Harousseau, J.-L., Ben-Yehuda, D., Lonial, S., Goldschmidt, H., Reece, D., Neuwirth, R., Anderson, K. C., Richardson, P. G.
(2008). Analysis of Herpes Zoster Events Among Bortezomib-Treated Patients in the Phase III APEX Study. JCO
26: 4784-4790
[Abstract][Full Text]
Fineschi, S., Bongiovanni, M., Donati, Y., Djaafar, S., Naso, F., Goffin, L., Barazzone Argiroffo, C., Pache, J.-C., Dayer, J.-M., Ferrari-Lacraz, S., Chizzolini, C.
(2008). In Vivo Investigations on Anti-Fibrotic Potential of Proteasome Inhibition in Lung and Skin Fibrosis. Am. J. Respir. Cell Mol. Bio.
39: 458-465
[Abstract][Full Text]
Rajkumar, S. V.
(2008). Treatment of Myeloma: Cure vs Control. Mayo Clin Proc.
83: 1142-1145
[Full Text]
Oerlemans, R., Franke, N. E., Assaraf, Y. G., Cloos, J., van Zantwijk, I., Berkers, C. R., Scheffer, G. L., Debipersad, K., Vojtekova, K., Lemos, C., van der Heijden, J. W., Ylstra, B., Peters, G. J., Kaspers, G. L., Dijkmans, B. A. C., Scheper, R. J., Jansen, G.
(2008). Molecular basis of bortezomib resistance: proteasome subunit {beta}5 (PSMB5) gene mutation and overexpression of PSMB5 protein. Blood
112: 2489-2499
[Abstract][Full Text]
Lunghi, P., Giuliani, N., Mazzera, L., Lombardi, G., Ricca, M., Corradi, A., Cantoni, A. M., Salvatore, L., Riccioni, R., Costanzo, A., Testa, U., Levrero, M., Rizzoli, V., Bonati, A.
(2008). Targeting MEK/MAPK signal transduction module potentiates ATO-induced apoptosis in multiple myeloma cells through multiple signaling pathways. Blood
112: 2450-2462
[Abstract][Full Text]
Argyriou, A. A., Iconomou, G., Kalofonos, H. P.
(2008). Bortezomib-induced peripheral neuropathy in multiple myeloma: a comprehensive review of the literature. Blood
112: 1593-1599
[Abstract][Full Text]
San Miguel, J. F., Schlag, R., Khuageva, N. K., Dimopoulos, M. A., Shpilberg, O., Kropff, M., Spicka, I., Petrucci, M. T., Palumbo, A., Samoilova, O. S., Dmoszynska, A., Abdulkadyrov, K. M., Schots, R., Jiang, B., Mateos, M.-V., Anderson, K. C., Esseltine, D. L., Liu, K., Cakana, A., van de Velde, H., Richardson, P. G., the VISTA Trial Investigators,
(2008). Bortezomib plus Melphalan and Prednisone for Initial Treatment of Multiple Myeloma. NEJM
359: 906-917
[Abstract][Full Text]
Sloss, C. M., Wang, F., Liu, R., Xia, L., Houston, M., Ljungman, D., Palladino, M. A., Cusack, J. C. Jr.
(2008). Proteasome Inhibition Activates Epidermal Growth Factor Receptor (EGFR) and EGFR-Independent Mitogenic Kinase Signaling Pathways in Pancreatic Cancer Cells. Clin. Cancer Res.
14: 5116-5123
[Abstract][Full Text]
van Rhee, F., Dhodapkar, M., Shaughnessy, J. D. Jr, Anaissie, E., Siegel, D., Hoering, A., Zeldis, J., Jenkins, B., Singhal, S., Mehta, J., Crowley, J., Jagannath, S., Barlogie, B.
(2008). First thalidomide clinical trial in multiple myeloma: a decade. Blood
112: 1035-1038
[Abstract][Full Text]
Koldehoff, M., Beelen, D. W., Elmaagacli, A. H.
(2008). Small-molecule inhibition of proteasome and silencing by vascular endothelial cell growth factor-specific siRNA induce additive antitumor activity in multiple myeloma. J. Leukoc. Biol.
84: 561-576
[Abstract][Full Text]
Markovina, S., Callander, N. S., O'Connor, S. L., Kim, J., Werndli, J. E., Raschko, M., Leith, C. P., Kahl, B. S., Kim, K., Miyamoto, S.
(2008). Bortezomib-Resistant Nuclear Factor-{kappa}B Activity in Multiple Myeloma Cells. Mol Cancer Res
6: 1356-1364
[Abstract][Full Text]
Waning, D. L., Li, B., Jia, N., Naaldijk, Y., Goebel, W. S., HogenEsch, H., Chun, K. T.
(2008). Cul4A is required for hematopoietic cell viability and its deficiency leads to apoptosis. Blood
112: 320-329
[Abstract][Full Text]
Utecht, K. N., Kolesar, J.
(2008). Bortezomib: A novel chemotherapeutic agent for hematologic malignancies. Am J Health Syst Pharm
65: 1221-1231
[Abstract][Full Text]
Bednarski, B. K., Ding, X., Coombe, K., Baldwin, A. S., Kim, H. J.
(2008). Active roles for inhibitory {kappa}B kinases {alpha} and {beta} in nuclear factor-{kappa}B-mediated chemoresistance to doxorubicin. Molecular Cancer Therapeutics
7: 1827-1835
[Abstract][Full Text]
Li, X., Pennisi, A., Yaccoby, S.
(2008). Role of decorin in the antimyeloma effects of osteoblasts. Blood
112: 159-168
[Abstract][Full Text]
Carew, J. S., Nawrocki, S. T., Reddy, V. K., Bush, D., Rehg, J. E., Goodwin, A., Houghton, J. A., Casero, R. A. Jr, Marton, L. J., Cleveland, J. L.
(2008). The Novel Polyamine Analogue CGC-11093 Enhances the Antimyeloma Activity of Bortezomib. Cancer Res.
68: 4783-4790
[Abstract][Full Text]
Palumbo, A., Gay, F., Bringhen, S., Falcone, A., Pescosta, N., Callea, V., Caravita, T., Morabito, F., Magarotto, V., Ruggeri, M., Avonto, I., Musto, P., Cascavilla, N., Bruno, B., Boccadoro, M.
(2008). Bortezomib, doxorubicin and dexamethasone in advanced multiple myeloma. Ann Oncol
19: 1160-1165
[Abstract][Full Text]
Wang, L., Kumar, S., Fridley, B. L., Kalari, K. R., Moon, I., Pelleymounter, L. L., Hildebrandt, M. A.T., Batzler, A., Eckloff, B. W., Wieben, E. D., Greipp, P. R.
(2008). Proteasome {beta} Subunit Pharmacogenomics: Gene Resequencing and Functional Genomics. Clin. Cancer Res.
14: 3503-3513
[Abstract][Full Text]
van Hees, H. W. H., Li, Y.-P., Ottenheijm, C. A. C., Jin, B., Pigmans, C. J. C., Linkels, M., Dekhuijzen, P. N. R., Heunks, L. M. A.
(2008). Proteasome inhibition improves diaphragm function in congestive heart failure rats. Am. J. Physiol. Lung Cell. Mol. Physiol.
294: L1260-L1268
[Abstract][Full Text]
Rajkumar, S. V., Rosinol, L., Hussein, M., Catalano, J., Jedrzejczak, W., Lucy, L., Olesnyckyj, M., Yu, Z., Knight, R., Zeldis, J. B., Blade, J.
(2008). Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Thalidomide Plus Dexamethasone Compared With Dexamethasone As Initial Therapy for Newly Diagnosed Multiple Myeloma. JCO
26: 2171-2177
[Abstract][Full Text]
Baritaki, S., Suzuki, E., Umezawa, K., Spandidos, D. A., Berenson, J., Daniels, T. R., Penichet, M. L., Jazirehi, A. R., Palladino, M., Bonavida, B.
(2008). Inhibition of Yin Yang 1-Dependent Repressor Activity of DR5 Transcription and Expression by the Novel Proteasome Inhibitor NPI-0052 Contributes to its TRAIL-Enhanced Apoptosis in Cancer Cells. J. Immunol.
180: 6199-6210
[Abstract][Full Text]
Chen, Q., Xie, W., Kuhn, D. J., Voorhees, P. M., Lopez-Girona, A., Mendy, D., Corral, L. G., Krenitsky, V. P., Xu, W., Moutouh-de Parseval, L., Webb, D. R., Mercurio, F., Nakayama, K. I., Nakayama, K., Orlowski, R. Z.
(2008). Targeting the p27 E3 ligase SCFSkp2 results in p27- and Skp2-mediated cell-cycle arrest and activation of autophagy. Blood
111: 4690-4699
[Abstract][Full Text]
Voorhees, P. M, Dees, E C., O'Neil, B., Orlowski, R. Z
(2008). The Proteasome as a Target for Cancer Therapy. aacredbook
2008: 153-170
[Abstract][Full Text]
Antczak, C., Radu, C., Djaballah, H.
(2008). A Profiling Platform for the Identification of Selective Metalloprotease Inhibitors. J Biomol Screen
13: 285-294
[Abstract]
Yan Hwang, Y., Chim, C.-S., Shek, T. W.H.
(2008). Multiple Myeloma With Testicular Involvement. JCO
26: 1558-1559
[Full Text]
Orlowski, R. Z., Kuhn, D. J.
(2008). Proteasome Inhibitors in Cancer Therapy: Lessons from the First Decade. Clin. Cancer Res.
14: 1649-1657
[Abstract][Full Text]
Kyle, R. A., Rajkumar, S. V.
(2008). Multiple myeloma. Blood
111: 2962-2972
[Abstract][Full Text]
Fojo, T.
(2008). Commentary: Novel Therapies for Cancer: Why Dirty Might Be Better. The Oncologist
13: 277-283
[Full Text]
Brenner, H., Gondos, A., Pulte, D.
(2008). Recent major improvement in long-term survival of younger patients with multiple myeloma. Blood
111: 2521-2526
[Abstract][Full Text]
Kumar, S. K., Rajkumar, S. V., Dispenzieri, A., Lacy, M. Q., Hayman, S. R., Buadi, F. K., Zeldenrust, S. R., Dingli, D., Russell, S. J., Lust, J. A., Greipp, P. R., Kyle, R. A., Gertz, M. A.
(2008). Improved survival in multiple myeloma and the impact of novel therapies. Blood
111: 2516-2520
[Abstract][Full Text]
Piva, R., Ruggeri, B., Williams, M., Costa, G., Tamagno, I., Ferrero, D., Giai, V., Coscia, M., Peola, S., Massaia, M., Pezzoni, G., Allievi, C., Pescalli, N., Cassin, M., di Giovine, S., Nicoli, P., de Feudis, P., Strepponi, I., Roato, I., Ferracini, R., Bussolati, B., Camussi, G., Jones-Bolin, S., Hunter, K., Zhao, H., Neri, A., Palumbo, A., Berkers, C., Ovaa, H., Bernareggi, A., Inghirami, G.
(2008). CEP-18770: A novel, orally active proteasome inhibitor with a tumor-selective pharmacologic profile competitive with bortezomib. Blood
111: 2765-2775
[Abstract][Full Text]
Agrawal, S. G., Liu, F.-T., Wiseman, C., Shirali, S., Liu, H., Lillington, D., Du, M.-Q., Syndercombe-Court, D., Newland, A. C., Gribben, J. G., Jia, L.
(2008). Increased proteasomal degradation of Bax is a common feature of poor prognosis chronic lymphocytic leukemia. Blood
111: 2790-2796
[Abstract][Full Text]
Jagannath, S.
(2008). Is tandem autotransplantation necessary in myeloma?. Blood
111: 1751-1752
[Full Text]
Shi, J., Tricot, G. J., Garg, T. K., Malaviarachchi, P. A., Szmania, S. M., Kellum, R. E., Storrie, B., Mulder, A., Shaughnessy, J. D. Jr, Barlogie, B., van Rhee, F.
(2008). Bortezomib down-regulates the cell-surface expression of HLA class I and enhances natural killer cell-mediated lysis of myeloma. Blood
111: 1309-1317
[Abstract][Full Text]
Chng, W. J., Braggio, E., Mulligan, G., Bryant, B., Remstein, E., Valdez, R., Dogan, A., Fonseca, R.
(2008). The centrosome index is a powerful prognostic marker in myeloma and identifies a cohort of patients that might benefit from aurora kinase inhibition. Blood
111: 1603-1609
[Abstract][Full Text]
Chauhan, D., Singh, A., Brahmandam, M., Podar, K., Hideshima, T., Richardson, P., Munshi, N., Palladino, M. A., Anderson, K. C.
(2008). Combination of proteasome inhibitors bortezomib and NPI-0052 trigger in vivo synergistic cytotoxicity in multiple myeloma. Blood
111: 1654-1664
[Abstract][Full Text]
Bensinger, W.
(2008). Stem-Cell Transplantation for Multiple Myeloma in the Era of Novel Drugs. JCO
26: 480-492
[Abstract][Full Text]
Matsui, W., Wang, Q., Barber, J. P., Brennan, S., Smith, B. D., Borrello, I., McNiece, I., Lin, L., Ambinder, R. F., Peacock, C., Watkins, D. N., Huff, C. A., Jones, R. J.
(2008). Clonogenic Multiple Myeloma Progenitors, Stem Cell Properties, and Drug Resistance. Cancer Res.
68: 190-197
[Abstract][Full Text]
Colado, E., Alvarez-Fernandez, S., Maiso, P., Martin-Sanchez, J., Vidriales, M. B., Garayoa, M., Ocio, E. M., Montero, J. C., Pandiella, A., San Miguel, J. F.
(2008). The effect of the proteasome inhibitor bortezomib on acute myeloid leukemia cells and drug resistance associated with the CD34+ immature phenotype. haematol
93: 57-66
[Abstract][Full Text]
Min, C.-K., Lee, M.-J., Eom, K.-S., Lee, S., Lee, J.-W., Min, W.-S., Kim, C.-C., Kim, M., Lim, J., Kim, Y., Han, K.
(2007). Bortezomib in Combination with Conventional Chemotherapeutic Agents for Multiple Myeloma Compared with Bortezomib Alone. Jpn J Clin Oncol
0: hym126v1-8
[Abstract][Full Text]
Weber, D. M., Chen, C., Niesvizky, R., Wang, M., Belch, A., Stadtmauer, E. A., Siegel, D., Borrello, I., Rajkumar, S. V., Chanan-Khan, A. A., Lonial, S., Yu, Z., Patin, J., Olesnyckyj, M., Zeldis, J. B., Knight, R. D., the Multiple Myeloma (009) Study Investigators,
(2007). Lenalidomide plus Dexamethasone for Relapsed Multiple Myeloma in North America. NEJM
357: 2133-2142
[Abstract][Full Text]
Richardson, P. G., Sonneveld, P., Schuster, M., Irwin, D., Stadtmauer, E., Facon, T., Harousseau, J.-L., Ben-Yehuda, D., Lonial, S., Goldschmidt, H., Reece, D., Miguel, J. S., Blade, J., Boccadoro, M., Cavenagh, J., Alsina, M., Rajkumar, S. V., Lacy, M., Jakubowiak, A., Dalton, W., Boral, A., Esseltine, D.-L., Schenkein, D., Anderson, K. C.
(2007). Extended follow-up of a phase 3 trial in relapsed multiple myeloma: final time-to-event results of the APEX trial. Blood
110: 3557-3560
[Abstract][Full Text]
Dingli, D., Pacheco, J. M., Nowakowski, G. S., Kumar, S. K., Dispenzieri, A., Hayman, S. R., Lacy, M. Q., Gastineau, D. A., Gertz, M. A.
(2007). Relationship Between Depth of Response and Outcome in Multiple Myeloma. JCO
25: 4933-4937
[Abstract][Full Text]
Dimopoulos, M. A., Souliotis, V. L., Anagnostopoulos, A., Bamia, C., Pouli, A., Baltadakis, I., Terpos, E., Kyrtopoulos, S. A., Sfikakis, P. P.
(2007). Melphalan-induced DNA damage in vitro as a predictor for clinical outcome in multiple myeloma. haematol
92: 1505-1512
[Abstract][Full Text]
Voorhees, P. M., Chen, Q., Kuhn, D. J., Small, G. W., Hunsucker, S. A., Strader, J. S., Corringham, R. E., Zaki, M. H., Nemeth, J. A., Orlowski, R. Z.
(2007). Inhibition of Interleukin-6 Signaling with CNTO 328 Enhances the Activity of Bortezomib in Preclinical Models of Multiple Myeloma. Clin. Cancer Res.
13: 6469-6478
[Abstract][Full Text]
Kuhn, D. J., Chen, Q., Voorhees, P. M., Strader, J. S., Shenk, K. D., Sun, C. M., Demo, S. D., Bennett, M. K., van Leeuwen, F. W. B., Chanan-Khan, A. A., Orlowski, R. Z.
(2007). Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma. Blood
110: 3281-3290
[Abstract][Full Text]
Garber, A. M., McClellan, M. B.
(2007). Satisfaction Guaranteed -- "Payment by Results" for Biologic Agents. NEJM
357: 1575-1577
[Full Text]
Rajkumar, S. V., Richardson, P. G., Lacy, M. Q., Dispenzieri, A., Greipp, P. R., Witzig, T. E., Schlossman, R., Sidor, C. F., Anderson, K. C., Gertz, M. A.
(2007). Novel Therapy with 2-Methoxyestradiol for the Treatment of Relapsed and Plateau Phase Multiple Myeloma. Clin. Cancer Res.
13: 6162-6167
[Abstract][Full Text]
Poulaki, V., Mitsiades, C. S., Kotoula, V., Negri, J., McMillin, D., Miller, J. W., Mitsiades, N.
(2007). The Proteasome Inhibitor Bortezomib Induces Apoptosis in Human Retinoblastoma Cell Lines In Vitro. IOVS
48: 4706-4719
[Abstract][Full Text]
Paiva, C. M., Kurtis, B., Mekki, M., Newman, M. A., Singhal, S., Lacouture, M. E.
(2007). Neutrophilic dermatitis associated with bortezomib in a patient with multiple myeloma. Ann Oncol
18: 1744-1745
[Full Text]
Rosinol, L., Oriol, A., Mateos, M. V., Sureda, A., Garcia-Sanchez, P., Gutierrez, N., Alegre, A., Lahuerta, J. J., de la Rubia, J., Herrero, C., Liu, X., Van de Velde, H., San Miguel, J., Blade, J.
(2007). Phase II Pethema Trial of Alternating Bortezomib and Dexamethasone As Induction Regimen Before Autologous Stem-Cell Transplantation in Younger Patients With Multiple Myeloma: Efficacy and Clinical Implications of Tumor Response Kinetics. JCO
25: 4452-4458
[Abstract][Full Text]
Palumbo, A., Falco, P., Corradini, P., Falcone, A., Di Raimondo, F., Giuliani, N., Crippa, C., Ciccone, G., Omede, P., Ambrosini, M. T., Gay, F., Bringhen, S., Musto, P., Foa, R., Knight, R., Zeldis, J. B., Boccadoro, M., Petrucci, M. T.
(2007). Melphalan, Prednisone, and Lenalidomide Treatment for Newly Diagnosed Myeloma: A Report From the GIMEMA Italian Multiple Myeloma Network. JCO
25: 4459-4465
[Abstract][Full Text]
Cavaletti, G., Nobile-Orazio, E.
(2007). Bortezomib-induced peripheral neurotoxicity: still far from a painless gain. haematol
92: 1308-1310
[Full Text]
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