Bortezomib in multiple myeloma

Expert Opinion on Drug Metabolism and Toxicology

Volumn 4, Issue 5, 2008, Pages 639-654

  Terpos, Evangelos ^a,b   Roussou, Maria ^c   Dimopoulos, Meletios Athanassios ^c  

^a 251 GENERAL AIR FORCE HOSPITAL   (Greece)

^b IMPERIAL COLLEGE LONDON   (United Kingdom)

^c UNIVERSITY OF ATHENS MEDICAL SCHOOL   (Greece)

Author keywords

Bone disease; Bortezomib; Frontline; Induction; Multiple myeloma; Proteasome inhibitors; Refractory; Relapsed

Indexed keywords

BISPHOSPHONIC ACID DERIVATIVE; BORTEZOMIB; CISPLATIN; CYCLOPHOSPHAMIDE; DEXAMETHASONE; DOXORUBICIN; ETOPOSIDE; GLUCOCORTICOID; I KAPPA B; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; LENALIDOMIDE; MELPHALAN; PREDNISONE; THALIDOMIDE; TUMOR NECROSIS FACTOR;

ABDOMINAL PAIN; ADULT RESPIRATORY DISTRESS SYNDROME; ANEMIA; ANGIONEUROTIC EDEMA; ANOREXIA; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTHRALGIA; AUTONOMIC NEUROPATHY; BONE DISEASE; BONE METABOLISM; BONE PAIN; BRAIN DISEASE; CANCER COMBINATION CHEMOTHERAPY; CANCER REGRESSION; CANCER RELAPSE; CANCER SURVIVAL; CHEMOTHERAPY INDUCED EMESIS; CHROMOSOME DELETION 13; CLINICAL TRIAL; COMBINATION CHEMOTHERAPY; CONSTIPATION; CONTROLLED CLINICAL TRIAL; COUGHING; DIARRHEA; DOSAGE SCHEDULE COMPARISON; DRUG APPROVAL; DRUG CLEARANCE; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG ELIMINATION; DRUG ERUPTION; DRUG FEVER; DRUG INDUCED HEADACHE; DRUG MEGADOSE; DRUG METABOLISM; DRUG SAFETY; DRUG WITHDRAWAL; DYSPNEA; FATIGUE; GASTROINTESTINAL SYMPTOM; HEART TAMPONADE; HERPES ZOSTER; HERPES ZOSTER OPHTHALMICUS; HUMAN; HYPERCALCEMIA; INSOMNIA; INTERSTITIAL PNEUMONIA; ISCHEMIC COLITIS; KIDNEY DYSFUNCTION; LIMB PAIN; LIVER FAILURE; MENINGOENCEPHALITIS; MONOTHERAPY; MULTIPLE CYCLE TREATMENT; MULTIPLE MYELOMA; MUSCLE CRAMP; NAUSEA; NEUROPATHY; NEUTROPENIA; OSTEOLYSIS; OVERALL SURVIVAL; PARESTHESIA; PERIPHERAL NEUROPATHY; PNEUMONIA; PROTEINASE INHIBITION; RANDOMIZED CONTROLLED TRIAL; RECOMMENDED DRUG DOSE; RETREATMENT; REVIEW; SPINAL CORD COMPRESSION; THROMBOCYTOPENIA; TREATMENT DURATION; TREATMENT OUTCOME; TREATMENT RESPONSE; UPPER RESPIRATORY TRACT INFECTION;

AGED; ANTINEOPLASTIC AGENTS; BORONIC ACIDS; CLINICAL TRIALS AS TOPIC; CLINICAL TRIALS, PHASE II AS TOPIC; CLINICAL TRIALS, PHASE III AS TOPIC; HUMANS; MULTIPLE MYELOMA; NEOPLASM RECURRENCE, LOCAL; PYRAZINES;

EID: 45949103359     PISSN: 17425255     EISSN: None     Source Type: Journal    
DOI: 10.1517/17425255.4.5.639     Document Type: Review

References (89)

1. Longo D, Andersen KC. Plasma cell disorders. In: Kasper DL, Braunwald E, Fauci AS, et al. editors, Harrison's principles of internal medicine, 16th edition. New York: McGraw-Hill; 2005. p. 656-62
2. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2007. CA Cancer J Clin 2007;57:43-66
3. NCCN clinical practice guidelines in oncology. Multiple myeloma. V.1.2008. Available from: http://www.nccn.org/professionals/ physician_gls/PDF/myeloma.pdf [Last accessed 4 April 2008]
4. Alexanian R, Barlogie B, Tucker S. VAD-based regimens as primary treatment for multiple myeloma. Am J Hematol 1990;33:86-9
5. Boccadoro M, Marmont F, Tribalto M, et al. Multiple myeloma: VMCP/VBAP alternating combination chemotherapy is not superior to melphalan and prednisone even in high-risk patients. J Clin Oncol 1991;9:444-8
6. Facon T, Mary JY, Pegourie B, et al. Dexamethasone-based regimens versus melphalan-prednisone for elderly multiple myeloma patients ineligible for high-dose therapy. Blood 2006;107:1292-8
7. Palumbo A, Bringhen S, Caravita T, et al. Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trial. Lancet 2006;367:825-31
8. Attal M, Harousseau JL, Stoppa AM, et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. N Engl J Med 1996;335:91-7
9. Child J, Morgan G, Davies F, et al. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med 2003;348:1875-83
10. Barlogie B, Kyle R, Anderson K, et al. Standard chemotherapy compared with high-dose chemoradiotherapy for multiple myeloma: final results of Phase III US Intergroup Trial S9321. J Clin Oncol 2006;24:929-36
11. Blade J, Rosinol L, Sureda A, et al. High-dose therapy intensification compared with continued standard chemotherapy in multiple myeloma patients responding to the initial chemotherapy: long-term results from a prospective randomized trial from the Spanish cooperative group PETHEMA. Blood 2005;106:3755-9
12. Zervas K, Mihou D, Katodritou E, et al. VAD-doxil versus VAD-doxil plus thalidomide as initial treatment for multiple myeloma: results of a multicenter randomized trial of the Greek Myeloma Study Group. Ann Oncol 2007;18:1369-75
13. Ludwig H, Tothova E, Drach J, et al. Thalidomide-dexamethasone versus melphalan-prednisolone as first line treatment in elderly patients with multiple myeloma: second interim analysis [abstract 446]. Haematologica 2007;92(Suppl 1)
14. Dimopoulos MA, Anagnostopoulos A, Terpos E, et al. Primary treatment with pulsed melphalan, dexamethasone and thalidomide for elderly symptomatic patients with multiple myeloma. Haematologica 2006;91:252-4
15. Palumbo A, Falco P, Corradini P, et al. Melphalan, prednisone, and lenalidomide treatment for newly diagnosed myeloma: a report from the GIMEMA Italian Multiple Myeloma Network. J Clin Oncol 2007;25:4459-65
16. Rajkumar SV, Blood E, Vesole D, et al. Phase III clinical trial of thalidomide plus dexamethasone compared with dexamethasone alone in newly diagnosed multiple myeloma: a clinical trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol 2006;24:431-6
17. Rajkumar SV, Hayman SR, Lacy MQ, et al. Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma. Blood 2005;106:4050-3
18. Kumar S, Dispenzieri A, Lacy MQ, et al. Impact of lenalidomide therapy on stem cell mobilization and engraftment post-peripheral blood stem cell transplantation in patients with newly diagnosed myeloma. Leukemia 2007;21:2035-42
19. Baz R, Walker E, Karam MA, et al. Lenalidomide and pegylated liposomal doxorubicin-based chemotherapy for relapsed or refractory multiple myeloma: safety and efficacy. Ann Oncol 2006;17:1766-71
20. Offidani M, Corvatta L, Marconi M, et al. Low-dose thalidomide with pegylated liposomal doxorubicin and high-dose dexamethasone for relapsed/ refractory multiple myeloma: a prospective, multicenter, Phase II study. Haematologica 2006;91:133-6
21. Chauhan D, Catley L, Li G, et al. A novel orally active proteasome inhibitor induces apoptosis in multiple myeloma cells with mechanisms distinct from Bortezomib. Cancer Cell 2005;8:407-19
22. Phase 1 clinical trial of NPI-0052 in patients with relapsed or relapsed/ refractory multiple myeloma. Available from: http://clinicaltrials.gov/ ct2/show/NCT00461045 [Last accessed 1 October 2007]
23. Adams J, Palombella VJ, Sausville EA, et al. Proteasome inhibitors: a novel class of potent and effective antitumor agents. Cancer Res 1999;59:2615-22
24. De Martino G, Slaughter C. The proteasome, a novel protease regulated by multiple mechanisms. J Biol Chem 1999;274:22123-6
25. Glickman M, Ciechanover A. The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol Rev 2002;82:373-428
26. Hideshima T, Chauhan D, Richardson P, et al. NF-kappa B as a therapeutic target in multiple myeloma. J Biol Chem 2002;277:16639-47
27. Armand J, Burnett A, Drach J, et al. The emerging role of targeted therapy for hematologic malignancies: update on bortezomib and tipifarnib. Oncologist 2007;12:281-90
28. 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;61:3071-6
29. Velcade (bortezomib) summary of product characteristics. Available from: http://www.emea.europa.eu/humandocs/PDFs/EPAR/velcade/H-539-PI-en.pdf [Last accessed 17 March 2008]
30. 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;20:4420-7
31. 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;127:165-72
32. Richardson PG, Barlogie B, Berenson J, et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med 2003;348:2609-17
33. Richardson PG, Barlogie B, Berenson J, et al. Extended follow-up of a Phase II trial in relapsed, refractory multiple myeloma: final time-to-event results from the SUMMIT trial. Cancer 2006;106:1316-9
34. Blade 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;102:1115-23
35. Richardson PG, Sonneveld P. Schuster MW et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med 2005;.352:2487-98
36. Richardson PG, Sonneveld P, Schuster M, et al. Extended follow-up of a phase 3 trial in relapsed multiple myeloma: final time-to-event results of the APEX trial. Blood 2007;110:3557-60
37. Harousseau JL, Nagler A, Sonneveld P, et al. Effect of the combination of pegylated lipsomal doxorubicin and bortezomib on time to progression (TTP) and overall survival of patients with relapsed/refractory multiple myeloma compared with bortezomib alone [abstract 8002]. J Clin Oncol 2007;25
38. Kropff M, Bisping G, Schuck E, et al. Bortezomib in combination with intermediate-dose dexamethasone and continuous low-dose oral cyclophosphamide for relapsed multiple myeloma. Br J Haematol 2007;138:330-7
39. Orlowski RZ, Nagler A, Sonneveld P, et al. Randomized Phase III study of pegylated liposomal doxorubicin plus bortezomib compared with bortezomib alone in relapsed or refractory multiple myeloma: combination therapy improves time to progression. J Clin Oncol 2007;25:3892-901
40. Palumbo A, Gay F, Falcone A, et al. Bortezomib, doxorubicin and dexamethasone (PAD) in advanced multiple myeloma [abstract PO-621]. Haematologica 2007;92
41. Popat R, Williams C, Cook M, et al. A Phase 1/II trial of bortezomib, low dose intravenous melphalan and dexamethasone for patients with relapsed multiple myeloma [abstract 3542]. Blood 2006;108
42. Terpos E, Anagnostopoulos A, Heath D, et al. The combination of bortezomib, melphalan, dexamethasone and intermittent thalidomide (VMDT) is an effective regimen for relapsed/refractory myeloma and reduces serum levels of Dickkopf-1, RANKL, MIP-1α and Angiogenic Cytokines [abstract 3541]. Blood 2006;108
43. Conner T, Doan Q, LeBlanc A, et al. An observational, retrospective analysis of retreatment with bortezomib of multiple myeloma (MM) patients [abstract 3531]. Blood 2006;108
44. Sood R, Carloss H, Kerr R, et al. Retreatment with bortezomib alone or in combination for patients with multiple myeloma (MM) following an initial response to bortezomib: a Phase IV, open-label trial [abstract 679P]. Ann Oncol 2007;17
45. Wolf JL, Richardson P, Schuster M, et al. Utility of bortezomib retreatment for patients with relapsed multiple myeloma [abstract 3532]. Blood 2006;108
46. Jagannath S, Dune BC, Wolf J, et al. Bortezomib therapy alone and in combination with dexamethasone for previously untreated symptomatic multiple myeloma. Br J Haematol 2005;129:776-83
47. Jagannath S, Durie BGM, Wolf JL, et al. Long-term follow-up of patients treated with bortezomib alone and in combination with dexamethasone as frontline therapy for multiple myeloma [abstract 796]. Blood 2006;108
48. Popat R, Oakervee H, Curry N, et al. Long term follow-up of PAD for untreated multiple myeloma [abstract PO-725]. Haematologica 2007;92
49. Rosinol L, Oriol A, Mateos MV, et al. Final results of a Phase II PETHEMA trial of alternating bortezomib and dexamethasone as induction regimen prior autologous stem cell transplantation (ASCT) in younger patients with multiple myeloma (MM): efficacy and clinical implications of tumour response kinetics [abstract S7b.1]. Haematologica 2007;92
50. Harousseau JL, Attal M, Leleu X, et al. Bortezomib plus dexamethasone as induction treatment prior to autologous stem cell transplantation in patients with newly diagnosed multiple myeloma: results of an IFM Phase II study. Haematologica 2006;91:1498-505
51. Barlogie B, Anaissie E, van RF, et al. Incorporating bortezomib into upfront treatment for multiple myeloma: early results of total therapy 3. Br J Haematol 2007;138:176-85
52. Jakubowiak A, Al-Zoubi A, Kendall T, et al. Combination therapy with bortezomib (Velcade®), Doxil®, and dexamethasone (VDD) in newly diagnosed myeloma: updated results of a Phase II clinical trial [abstract PO-721]. Haematologica 2007;92(Suppl 2)
53. 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;129:755-62
54. Richardson RG, Jagannath S, Raje NS, et al. Phase 1/2 study of upfront rev/vel/dex in mm: early results [abstract PO-715]. Haematologica 2007;92
55. Harousseau JL, Mathiot C, Attal M, et al. VELCADE/dexamethasone (Vel/D) versus VAD as induction treatment prior to autologous stem cell tTransplantion (ASCT) in newly diagnosed multiple myeloma (MM): updated results of the IFM 2005/01 trial [abstract 450]. Blood 2007;110
56. Cavo M, Patriarca F, Tacchetti P, et al. Bortezomib (velcade)-thalidomide-dexamethasone (VTD) vs thalidomide-dexamethasone (TD) in preparation for autologous stem-cell (SC) transplantation (ASCT) in newly diagnosed multiple myeloma (MM) [abstract 73]. Blood 2007;110
57. Ladetto M, Pagliano G, Avonto I, et al. Consolidation with bortezomib, thalidomide and dexamethasone induces molecular remissions in autografted multiple myeloma patients. Blood 2007;110:530
58. Mateos MV, Hernandez JM, Hernandez MT, et al. Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: results of a multicenter phase 1/2 study. Blood 2006;108:2165-22
59. Mateos MV, Hernandez JM, Hernandez MT, et al. Frontline VMP in elderly MM patients: extended follow-up [abstract PO-718]. Haematologica 2007;92
60. San Miguel JF, Schlag R, Khuageva N, et al. MMY-3002: a phase-3 study comparing bortezomib-melphalan-prednisone with melphalan-prednisone in newly-diagnosed multiple myeloma [abstract 76]. Blood 2007;110
61. Velcade as maintenance treatment in patients with multiple myeloma following autologous peripheral blood stem cell transplantation (PBSCT). Available from: http://clinicaltrials.gov/ct2/show/ NCT00311337?term=bortezomib+maintenance+myeloma&rank=2 [Last accessed 17 March 2008]
62. Adjuvant bortezomib maintenance therapy after autologous peripheral stem cell transplantation in treating patients with intermediate on advanced multiple myeloma. Available from: http://clinicaltrials.gov/ct2/show/ NCT00084747?term=bortezomib+maintenance+myeloma&rank=1 [Last accessed 17 March 2008]
63. Bortezomib and dexamethasone as treatment and maintenance for multiple myeloma relapse. Available from: http://clinicaltrials.gov/ct2/show/ NCT00335348?term=bortezomib+maintenance+myeloma&rank=4 [Last accessed 17 March 2008]
64. 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;103:1195-200
65. San Miguel JF, Richardson PG, Sonneveld P, et al. Bortezomib in renally impaired multiple myeloma patients [abstract PO-1114]. Haematologica 2007;92
66. Chanan-Khan AA, Kaufman JL, Mehta J, et al. Activity and safety of bortezomib in multiple myeloma patients with advanced renal failure: a multicenter retrospective study. Blood 2007;109:2604-6
67. Terpos E, Katodritou E, Tsiftsakis E, et al. Cystatin-C: an early marker of renal impairment and an independent predictive factor for survival in multiple myeloma. Reduction post bortezomib therapy [abstract PO-227]. Haematologica 2007;92
68. Knudsen LM, Hjorth M, Hippe E. Renal failure in multiple myeloma: reversibility and impact on the prognosis. Nordic Myeloma Study Group. Eur J Haematol 2000;65:175-81
69. Jagannath S, Richardson PG, Sonneveld P, et al. Bortezomib appears to overcome the poor prognosis conferred by chromosome 13 deletion in phase 2 and 3 trials. Leukemia 2007;21:151-7
70. Sagaster V, Ludwig H, Kaufmann H, et al. Bortezomib in relapsed multiple myeloma: response rates and duration of response are independent of a chromosome 13q-deletion. Leukemia 2007;21:164-8
71. Terpos E, Dimopoulos MA. Myeloma bone disease: pathophysiology and management. Ann Oncol 2005;16:1223-31
72. Terpos E, Dimopoulos MA, Sezer O. The effect of novel anti-myeloma agents on bone metabolism of patients with multiple myeloma. Leukemia 2007;21:1875-84
73. Giuliani N, Morandi F, Tagliaferri S, et al. The proteasome inhibitor bortezomib affects osteoblast differentiation in vitro and in vivo in multiple myeloma patients. Blood 2007;110:334-8
74. Boissy P, Lund T, Andersen TL, et al. Intermittent treatment with bortezomib inhibits transiently osteoclast resorptive activity [abstract PO-315]. Haematologica 2007; 92(Suppl 2)
75. Lonial S, Richardson P, Sonneveld P, et al. Hematologic profiles in the Phase 3 APEX trial [abstract 3474]. Blood 2005;106
76. Peles S, Fisher NM, Gao F, et al. A prospective study of the effects of once weekly bortezomib on markers of bone metabolism in patients with multiple myeloma [abstract 7548]. J Clin Oncol 2006;24
77. Terpos E, Heath DJ, Rahemtulla A, et al. Bortezomib reduces serum dickkopf-1 and receptor activator of nuclear factor-kappaB ligand concentrations and normalises indices of bone remodelling in patients with relapsed multiple myeloma. Br J Haematol 2006;135:688-92
78. Terpos E, Heath DJ, Zervas K, et al. The effect of bortezomib monotherapy and bortezomib-based regimens on bone metabolism in patients with relapsed/refractory multiple myeloma [abstract PO-320]. Haematologica 2007;92
79. Ozaki S, Tanaka O, Fujii S, et al. Therapy with bortezomib plus dexamethasone induces osteoblast activation in responsive patients with multiple myeloma. Int J Hematol 2007;86:180-5
80. Heider U, Kaiser M, Muller C, et al. Bortezomib increases osteoblast activity in myeloma patients irrespective of response to treatment. Eur J Haematol 2006;77:233-8
81. Zangari M, Yaccoby S, Suva L, et al. Prospective evaluation of bone histomorphometric changes associated to bortezomib in multiple myeloma patients. Haematologica 2007;92:Abstract 695
82. Terpos E, Sezer O, Croucher P, Dimopoulos MA. Myeloma bone disease and proteasome inhibition therapies. Blood 2007;110:1098-104
83. Moreau P, Coiteux V, Hulin C, et al. Prospective comparison of subcutaneous to intravenous administration of bortezomib in patients with multiple myeloma: Pharmacokinetics, efficacy and toxicity. J Clin Oncol 2007;25:8046
84. San Miguel JF, Richardson P, Sonneveld P, et al. Frequency, characteristics, and reversibility of peripheral neuropathy (PN) in the APEX trial [abstract 366]. Blood 2005;106
85. Lonial S, Walters I, Richardson P, et al. Risk factors and kinetics of thrombocytopenia associated with bortezomib for relapsed, refractory multiple myeloma. Blood 2005;106:3777-84
86. San Miguel J, Blade J, Boccadoro M, et al. A practical update on the use of bortezomib in the management of multiple myeloma. Oncologist 2006;11:51-61
87. Velcade label (May 2003). Available from: http://www.fda.gov/cder/foi/ label/2003/021602lbl.pdf [Last accessed 17 March 2008]
88. Doxorubicin HCl liposome injection (Doxil) is approved for patients with multiple myeloma. Available from: http://www.fda.gov/cder/Offices/OODP/ whatsnew/doxorubicin.htm [Last accessed 17 March 2008]
89. Badros A, Goloubeva O, Dalal J, et al. Neurotoxicity of bortezomib therapy in multiple myeloma: a single-center experience and review of the literature. Cancer 2007;110:1042-9