Cancer Treatment Reviews
Volume 31, Issue 8 , Pages 591-602 , December 2005

Bortezomib, a novel proteasome inhibitor, in the treatment of hematologic malignancies

  • Graham Jackson

      Affiliations

    • Department of Haematology, Royal Victoria Infirmary, Queen Victoria Road, Newcastle Upon Tyne NE1 4LP, United Kingdom
    • Corresponding Author InformationCorresponding author. Tel.: +44 191 2336161.
  • ,
  • Hermann Einsele

      Affiliations

    • Department of Haematology and Oncology, Julius-Maximilians-University of Würzburg, Medizinische Klinik und Poliklinik II, Würzburg, Germany
  • ,
  • Phillippe Moreau

      Affiliations

    • Department of Clinical Hematology, University Hospital, Nantes, France
  • ,
  • Jesus San Miguel

      Affiliations

    • Department of Hematology, University Hospital of Salamanca, Paso de San Vicente 52-182, 37007 Salamanca, Spain

References 

  1. Garber K. Cancer research. Taking garbage in, tossing cancer out. Science. 2002;295(5555):612–613
  2. Adams J. Proteasome inhibition: a novel approach to cancer therapy. Trends Mol Med. 2002;8(4 Suppl):S49–S54
  3. Glickman MH, Ciechanover A. The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol Rev. 2002;82(2):373–428
  4. Williams S, Pettaway C, Song R, Papandreou C, Logothetis C, McConkey DJ. Differential effects of the proteasome inhibitor bortezomib on apoptosis and angiogenesis in human prostate tumour xenografts. Mol Cancer Ther. 2003;2(9):835–843
  5. King RW, Deshaies RJ, Peters JM, Kirschner MW. How proteolysis drives the cell cycle. Science. 1996;274(5293):1652–1659
  6. Mitsiades N, Mitsiades CS, Poulaki V, et al. Molecular sequelae of proteasome inhibition in human multiple myeloma cells. Proc Natl Acad Sci USA. 2002;99(22):14374–14379
  7. Adams J. Proteasome inhibition in cancer: development of PS-341. Semin Oncol. 2001;28(6):613–619
  8. Adams J, Palombella VJ, Sausville EA, et al. Proteasome inhibitors: a novel class of potent and effective antitumour agents. Cancer Res. 1999;59(11):2615–2622
  9. Yang HH, Ma MH, Vescio RA, Berenson JR. Overcoming drug resistance in multiple myeloma: the emergence of therapeutic approaches to induce apoptosis. J Clin Oncol. 2003;21(22):4239–4247
  10. Frankel A, Man S, Elliott P, Adams J, Kerbel RS. Lack of multicellular drug resistance observed in human ovarian and prostate carcinoma treated with the proteasome inhibitor PS-341. Clin Cancer Res. 2000;6(9):3719–3728
  11. Kamat AM, Karashima T, Davis DW, et al. The proteasome inhibitor bortezomib synergizes with gemcitabine to block the growth of human 253JB-V bladder tumours in vivo. Mol Cancer Ther. 2004;3(3):279–290
  12. Mitsiades N, Mitsiades CS, Richardson PG, et al. The proteasome inhibitor PS-341 potentiates sensitivity of multiple myeloma cells to conventional chemotherapeutic agents: therapeutic applications. Blood. 2003;101(6):2377–2380
  13. Yu C, Rahmani M, Conrad D, Subler M, Dent P, Grant S. The proteasome inhibitor bortezomib interacts synergistically with histone deacetylase inhibitors to induce apoptosis in Bcr/Abl+ cells sensitive and resistant to STI571. Blood. 2003;102(10):3765–3774
  14. Berenson J, Yang H, Swift R, et al. A phase I/II trial of VELCADE and melphalan combination therapy (Vc+M) for patients with relapsed or refractory multiple myeloma (MM). Blood. 2004;104(11):64a
  15. Richardson PG, Barlogie B, Berenson J, et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med. 2003;348(26):2609–2617
  16. Orlowski RZ, Voorhees PM, Garcia RA, et al. Phase 1 trial of the proteasome inhibitor bortezomib and pegylated liposomal doxorubicin in patients with advanced hematologic malignancies. Blood. 2005;105(8):3058–3065
  17. Adams J, Palombella VJ, Elliott PJ. Proteasome inhibition: a new strategy in cancer treatment. Invest New Drugs. 2000;18(2):109–121
  18. Delcros JG, Floc’h MB, Prigent C, Arlot-Bonnemains Y. Proteasome inhibitors as therapeutic agents: current and future strategies. Curr Med Chem. 2003;10(6):479–503
  19. Adams J, Behnke M, Chen S, et al. Potent and selective inhibitors of the proteasome: dipeptidyl boronic acids. Bioorg Med Chem Lett. 1998;8(4):333–338
  20. Kisselev AF, Goldberg AL. Proteasome inhibitors: from research tools to drug candidates. Chem Biol. 2001;8(8):739–758
  21. Karin M, Cao Y, Greten FR, Li ZW. NF-kappaB in cancer: from innocent bystander to major culprit. Nat Rev Cancer. 2002;2(4):301–310
  22. Wang CY, Mayo MW, Baldwin AS. TNF- and cancer therapy-induced apoptosis: potentiation by inhibition of NF-kappaB. Science. 1996;274(5288):784–787
  23. Wang CY, Cusack JC, Liu R, Baldwin AS. Control of inducible chemoresistance: enhanced anti-tumour therapy through increased apoptosis by inhibition of NF-kappaB. Nat Med. 1999;5(4):412–417
  24. Cusack JC, Liu R, Houston M, et al. Enhanced chemosensitivity to CPT-11 with proteasome inhibitor PS-341: implications for systemic nuclear factor-kappaB inhibition. Cancer Res. 2001;61(9):3535–3540
  25. Russo SM, Tepper JE, Baldwin AS, et al. Enhancement of radiosensitivity by proteasome inhibition: implications for a role of NF-kappaB. Int J Radiat Oncol Biol Phys. 2001;50(1):183–193
  26. Hideshima T, Richardson P, Chauhan D, et al. The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma cells. Cancer Res. 2001;61(7):3071–3076
  27. Hideshima T, Mitsiades C, Akiyama M, et al. Molecular mechanisms mediating antimyeloma activity of proteasome inhibitor PS-341. Blood. 2003;101(4):1530–1534
  28. Ma MH, Yang HH, Parker K, et al. The proteasome inhibitor PS-341 markedly enhances sensitivity of multiple myeloma tumour cells to chemotherapeutic agents. Clin Cancer Res. 2003;9(3):1136–1144
  29. LeBlanc R, Catley LP, Hideshima T, et al. Proteasome inhibitor PS-341 inhibits human myeloma cell growth in vivo and prolongs survival in a murine model. Cancer Res. 2002;62(17):4996–5000
  30. Pham LV, Tamayo AT, Yoshimura LC, Lo P, Ford RJ. Inhibition of constitutive NF-kappa B activation in mantle cell lymphoma B cells leads to induction of cell cycle arrest and apoptosis. J Immunol. 2003;171(1):88–95
  31. Chauhan D, Li G, Shringarpure R, et al. Blockade of Hsp27 overcomes Bortezomib/proteasome inhibitor PS-341 resistance in lymphoma cells. Cancer Res. 2003;63(19):6174–6177
  32. Orlowski RZ, Eswara JR, Lafond-Walker A, Grever MR, Orlowski M, Dang CV. Tumour growth inhibition induced in a murine model of human Burkitt’s lymphoma by a proteasome inhibitor. Cancer Res. 1998;58(19):4342–4348
  33. Aghajanian C, Soignet S, Dizon DS, et al. A phase I trial of the novel proteasome inhibitor PS341 in advanced solid tumour malignancies. Clin Cancer Res. 2002;8(8):2505–2511
  34. Orlowski RZ, Stinchcombe TE, Mitchell BS, et al. Phase I trial of the proteasome inhibitor PS-341 in patients with refractory hematologic malignancies. J Clin Oncol. 2002;20(22):4420–4427
  35. Papandreou C, Daliani KK, Nix D, et al. Phase I trial of the proteasome inhibitor bortezomib in patients with advanced solid tumours with observations in androgen-independent prostate cancer. J Clin Oncol. 2004;22:2108–2121
  36. Lightcap ES, McCormack TA, Pien CS, Chau V, Adams J, Elliott PJ. Proteasome inhibition measurements: clinical application. Clin Chem. 2000;46(5):673–683
  37. Adams J. Development of the proteasome inhibitor PS-341. Oncologist. 2002;7(1):9–16
  38. Richardson PG, Barlogie B, Berenson J, et al. Survival, duration of response, and time to progression with bortezmib in patients with relapsed and refractory multiple myeloma: an update with additional follow-up. Hematol J. 2004;5(Suppl 2):S103–S104
  39. Berenson JR, Jagannath S, Barlogie B, et al. The safety of prolonged therapy with the proteasome inhibitor bortezomib (VELCADE) in relapsed and/or refractory multiple myeloma (MM). Hematol J. 2004;5(Suppl 2):S129
  40. Jagannath S, Barlogie B, Berenson J, et al. A phase 2 study of two doses of bortezomib in relapsed or refractory myeloma. Br J Haematol. 2004;127(2):165–172
  41. Richardson PG, Sonneveld P, Schuster MW, et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med. 2005;352(24):2487–2498
  42. Sonneveld P, Richardson PG, Schuster MW, et al. Bortezomib at first relapse is superior to high-dose dexamethasone and mnore effective than when given later in relapsed multiple myeloma. Haematologica. 2005;90(Suppl 1):s1–s2
  43. Jagannath S, Richardson P, Barlogie B, et al. Bortezomib in combination with dexamethasone for the treatment of patients with relapsed and/or refractory multiple myeloma. Hematol J. 2004;5(Suppl 2):S130
  44. Hollmig K, Stover J, Talamo G, et al. Bortezomib Velcade™)+Adriamycin™+thalidomide+dexamethasone (VATD) as an effective regimen in patients with refractory or relapsed multiple myeloma (MM). Blood. 2004;104(11):659a
  45. Chanan-Khan A, Miller KC, McCarthy P, et al. A phase II study of Velcade (V), Doxil (D) in combination with low-dose thalidomide (T) as salvage therapy for patients (pts) with relapsed (rel) or refractory (ref) multiple myeloma (MM) and Waldenstrom’s macroglobulinemia (WM): encouraging preliminary results. Blood. 2004;104(11):665a–666a
  46. Zangari M, Barlogie B, Hollmig K, et al. Marked activity of Velcade plus thalidomide (V+T) in advanced and refractory multiple myeloma (MM). Blood. 2004;104(11):413a–414a
  47. Jagannath S, Wolf H, Camacho E, et al. Bortezomib therapy alone and in combination with dexamethasone for previously untreated symptomatic multiple myeloma. Br J Haematol. 2005;129(6):776–783
  48. Oakervee HE, Popat R, Curry N, et al. PAD combination therapy (PS-341/bortezomib, doxorubicin and dexamethasone) for previously untreated patients with multiple myeloma. Br J Haematol. 2005;129(6):755–762
  49. Harousseau JL, Attal M, Coiteaux V, et al. Bortezomib (VELCADE) plus dexamethasone as induction treatment prior to autologous stem cell transplantation in patients with newly diagnosed multiple myeloma: preliminary results of an IFM phase II study. J Clin Oncol. 2005;23(16S):598s
  50. Alexanian R, Wang LW, Weber DM, Delasalle KB. VTD (Velcade, thalidomide, dexamethasone) as primary therapy for newly-diagnosed multiple myeloma. Blood. 2004;104(11):64a
  51. Mateos MV, Blade J, Mediavilla JD, et al. A phase I/II national, multi-center, open-label study of Velcade plus melphalan and prednisone (V-MP) in elderly untreated multiple myeloma patients. Haematologica. 2005;90(Suppl 1):149
  52. Jagannath S, Barlogie B, Berenson JR, et al. Bortezomib in recurrent and/or refractory multiple myeloma: initial clinical experience in patients with impaired renal function. Cancer. 2005;103(6):1195–1200
  53. VELCADE (bortezomib) for injection. Full prescribing information available at: http://www.millenniumcom/products/velcade/indexasp; 2004. Accessed February 24, 2005.
  54. Richardson PG, Briemberg H, Jagannath S, et al. Characterization and reversibility of peripheral neuropathy in patients with advanced multiple myeloma treated with bortezomib (VELCADE): the SUMMIT and CREST study group. Hematol J. 2004;5(2):S129
  55. Goy A, Younes A, McLaughlin P, et al. Phase II study of proteasome inhibitor bortezomib in relapsed or refractory B-cell non-Hodgkin’s lymphoma. J Clin Oncol. 2005;23(4):667–675
  56. O’Connor OA, Wright J, Moskowitz C, et al. Phase II clinical experience with the novel proteasome inhibitor bortezomib in patients with indolent non-Hodgkin’s lymphoma and mantle cell lymphoma. J Clin Oncol. 2005;23(4):676–684
  57. Belch A, Kourakis CT, Crump M, et al. Phase II trial of bortezomib in mantle cell lymphoma. Blood. 2004;104(11):175a
  58. Strauss SJ, Maharaj L, Stec J, et al. Phase II clinical study of bortezomib (VELCADE®) in patients (pts) with relapsed/refractory non-Hodgkin’s lymphoma (NHL) and Hodgkin’s disease (HD). Blood. 2004;104(11):389a
  59. Dunleavy K, Janik J, Gea-Banacloche J, et al. Phase I/II study of bortezomib alone and bortezomib with dose-adjusted EPOCH chemotherapy in relapsed or refractory aggressive B-Cell lymphoma. Blood. 2004;104(11):389a
  60. Younes A, Pro B, Romaguera J, Dang N. Safety and efficacy of bortezomib (VELCADE®) for the treatment of relapsed classical Hodgkin’s disease. Blood. 2004;104(11):722a
  61. Cortes J, Thomas D, Koller C, et al. Phase I study of bortezomib in refractory or relapsed acute leukemias. Clin Cancer Res. 2004;10(10):3371–3376
  62. Attar EC, Learner E, Amrein PC. Phase I dose-escalating trial of bortezomib (VELCADE®) in combination with idarubicin and cytosine arabinoside in patients with acute myeloid leukemia. Blood. 2004;104(11):498a
  63. Mehta J, Duff SB, Gupta S. Cost effectiveness of bortezomib in the treatment of advanced multiple myeloma. Manag Care Interface. 2004;17(9):52–61
  64. Bagust A, Haycox AR, Boland A, et al. Economic evaluation of bortezomib (Velcade) for relapsed and refractory multiple myeloma. Blood. 2004;104(11):80a
  65. Laupacis A, Feeny D, Detsky AS, Tugwell PX. How attractive does a new technology have to be to warrant adoption and utilization? Tentative guidelines for using clinical and economic evaluations. CMAJ. 1992;146(4):473–481
  66. Messori A, Trippoli S, Vaiani M. Efficacy, safety, and cost of new anticancer drugs. BMJ. 2005;325:1302
  67. Barlogie B, Desikan R, Eddlemon P, et al. Extended survival in advanced and refractory multiple myeloma after single-agent thalidomide: identification of prognostic factors in a phase 2 study of 169 patients. Blood. 2001;98(2):492–494
  68. Hussein MA, Saleh M, Ravandi F, Mason J, Rifkin RM, Ellison R. Phase 2 study of arsenic trioxide in patients with relapsed or refractory multiple myeloma. Br J Haematol. 2004;125(4):470–476
  69. Gertz MA, Lacy MQ, Inwards DJ, et al. Delayed stem cell transplantation for the management of relapsed or refractory multiple myeloma. Bone Marrow Transplant. 2000;26(1):45–50
  70. Bladé J, Samson D, Reece D, et al. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant. Br J Haematol. 1998;102(5):1115–1123

PII: S0305-7372(05)00199-4

doi: 10.1016/j.ctrv.2005.10.001

Cancer Treatment Reviews
Volume 31, Issue 8 , Pages 591-602 , December 2005