硼替佐米治疗多发性骨髓瘤的应用进展_West China Medical Journal

Authors：

何东 ^1,2 ,  牛挺 ¹

Corresponding author：

牛挺, Email: hedong09@163.com

Keywords：

多发性骨髓瘤; 硼替佐米; 治疗

DOI：

CNKI: 51-1356/R.20120214.1339.009

Video：

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多发性骨髓瘤（MM）作为中老年常见的血液肿瘤之一，预后相对较差，常规化学疗法（化疗）疗效欠理想。硼替佐米作为一种新药，属于蛋白酶体抑制剂，通过全新的机制达到抗骨髓瘤的作用。国内外临床研究表明硼替佐米单药以及同常规化疗药物组成的联合化疗方案对初始治疗，以及复发难治的MM患者均有良好疗效。因此以硼替佐米为主的联合化疗方案已被美国国家综合癌症协作网推荐作为MM患者治疗的重要选择之一。现将硼替佐米在MM治疗上的进展作一综述。

Citation： 何东,牛挺. 硼替佐米治疗多发性骨髓瘤的应用进展. West China Medical Journal, 2012, 27(2): 197-202. doi: CNKI: 51-1356/R.20120214.1339.009 Copy

1.	叶任高, 陆再英. 内科学[M]. 6版. 北京: 人民卫生出版社, 2004: 631.
2.	高玉环, 刘海生. 血液系统恶性肿瘤现代非手术治疗[M]. 北京: 科技文献出版社, 2008: 157-158.
3.	张晓辉, 黄晓军. 造血干细胞移植治疗多发性骨髓瘤的研究进展 [J]. 国际输血及血液学杂志, 2007, 30(4): 328-331.
4.	Kenneth CA, Melissa A, William B, et al. NCCN clinical practice guidelines in oncology multiple myeloma version I[S]. 2011: 17.
5.	Reeder CB, Reece DE, Kukreti V, et al. Cyclophosphamide, bortezomib and dexamethasone induction for newly diagnosed multiple myeloma: high response rates in a phase Ⅱ clinical trial[J]. Leukemia, 2009, 23(7): 1337-1341.
6.	Hideshima T, Miltiades C, Akiyama M, et al. Molecular mechanisms mediating antimyeloma activity of proteasome inhibitor PS-341[J]. Blood, 2003, 101(4): 1530-1534.
7.	Jullig M, Zhang WV, Ferreira A, et al. MG132 induced apoptosis is associated with P53-independent induction of pro-apoptotic NOXA and transcriptional activity of beta-catenin [J]. Apoptosis, 2006, 11(4): 627-641.
8.	Roccaro AM, Hideshima T, Raje N, et al. Bortezomib mediates antiangi ogenesis in multiple myeloma via direct and indirect effects on endothelia1 cells[J]. Cancer Ras, 2006, 66(1): 184-191.
9.	National Comprehensive Cancer Net work (NCCN). NCCN clinical practice guidelines in oncology TM multiple myeloma (V.3.2008).http//www. nccn.org/peofessionals/physician_gle/PDF/myeloma.pdf.
10.	National Comprehensive Cancer Net work(NCCN). NCCN clinical practice guidelines in oncology multiple myeloma (V.1.2011). http://www.nccn.org/peofessionals/physician_gle/PDF/myeloma.pdf.
11.	Jagannath S, Durie BG, Wolf J, et al. Bortezomib therapy alone and in combination with dexamethasone for previously untreated symptomatic multiple myeloma[J]. Br J Haematol, 2005, 129(6): 776-783.
12.	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[J]. Haematologica, 2006, 91(11): 1498-1505.
13.	Harousseau JL , Attal M , Avet-Loiseau H , et al. Bortezomib plus dexamethasone is superior to vincristine plus doxorubicin plus dexamethasone as induction treatment prior to autologous stem-cell transplantation in newly diagnosed multiple myeloma: results of the IFM 2005-01 phase Ⅲ trial[J]. J Clin Oncol, 2010, 28(30): 4621-4629.
14.	Corso A , Barbarano L , Mangiacavalli S , et al. Bortezomib plus dexamethasone can improve stem cell collection and overcome the need for additional chemotherapy before autologous transplant in patients with myeloma[J]. Leuk Lymphoma, 2010, 51(2): 236-242.
15.	Cavo M, Tacchetti P, Patriarca F, et al. Superior complete response rate and progression-free survival after autologous transplantation with up-front velcade-thalidomide-dexamethasone compared with thalidomide-dexamethasone in newly diagnosed multiple myeloma[J]. Blood, 2008, 112(11): 65.
16.	Sonneveld P, van der Holt B, Schmidt-Wolf IGH, et al. First analysis of HOVON-65/GMMG-HD4 randomized phase Ⅲ trial comparing bortezomib, adriamycine, dexamethasone (pad) vs vad as induction treatment prior to high dose melphalan (HDM) in patients with newly diagnosed multiple myeloma (MM)[J]. ASH Annual Meeting Abstracts, 2008, 112(11): 653.
17.	Rajkumar SV, Hayman SR,Lacy MQ, et al. Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma[J]. Blood, 2005, 106(13): 4050-4053.
18.	Richardson P, Lonial S, Jakubowiak A, et al. Lenalidomide, bortezomib,and dexamethasone in patients with newly diagnosed multiple myeloma:encouraging effcacy in high risk Groups with updated results of a phaseⅠ/Ⅱ study[J]. ASH Annual Meeting Abstracts, 2008,112(11): 92.
19.	Corso A , Barbarano L , Mangiacavalli S , et al. Bortezomib plus dexamethasone can improve stem cell collection and overcome the need for additional chemotherapy before autologous transplant in patients with myeloma [J]. Leuk Lymphoma, 2010, 51(2): 236-242.
20.	何东, 刘志刚, 喻琴梅, 等. 硼替佐米提高多发性骨髓瘤干细胞采集的临床研究[J]. 华西医学, 2011, 26(4): 521-523.
21.	Chari A, Mazumder M, Jagannath S. Proteasome inhibition and its therapeutic potential in multiple myeloma[J]. Biologics: Targets & Therapy, 2010, 4(10): 273-287.
22.	Mateos MV, Richardson PG, Schlag R, et al. Bortezomib plus melphalan and prednisone compared with melphalan and prednisone in previously untreated multiple myeloma: updated follow-up and impact of subsequent therapy in the phase Ⅲ VISTA trial[J]. J Clin Oncol, 2010, 28(13): 2259-2266.
23.	Palumbo A, Bringhen S, Rossi D, et al. A prospective, randomized, phase Ⅲ study of bortezomib, melphalan, prednisone and thalidomide (VMPT) versus bortezomib, melphalan and prednisone (VMP) in elderly newly diagnosed myeloma patients[J]. ASH Annual Meeting Abstracts, 2008, 112(11): 652.
24.	Rotta M, Storer BE, Sahebi F, et al. Long-term outcomeof patients with multiple myeloma after autologous hematopoietic cell transplantation and nonmyeloablative allografting[J]. Blood, 2009, 113(14): 3383-3391.
25.	Mandelli F, Avvisati G, Amadori S, et al. Maintenance treatment with recombinant interferon alfa-2b inpatients with multiple myeloma responding to conventional induction chemotherapy[J]. N Engl J Med,1990, 322(10): 1430-1434.
26.	Berenson JR, Crowley JJ, Grogan TM, et al. Maintenance therapy with alternate-day prednisone improves survival in multiple myeloma patients[J]. Blood, 2002, 99(9): 3163-3168.
27.	Spencer A, Prince HM, Roberts AW, et al. Consolidation therapy with low-dose thalidomide and prednisolone prolongs the survival of multiple myeloma patients undergoing a single autologous stem-cell transplantation procedure[J]. J Clin Oncol, 2009, 27(11): 1788-1793.
28.	Attal M, Harousseau JL, Leyvraz S, et al. Maintenanc therapy with thalidomide improves survival in patients with multiple myeloma[J]. Blood, 2006, 108(10): 3289-3294.
29.	Dispenzieri A , Jacobus S , Vesole DH , et al. Primary therapy with single agent bortezomib as induction, maintenance and re-induction in patients with high-risk myeloma: results of the ECOG E2A02 trial[J]. Leukemia , 2010, 24(8): 1406-1411.
30.	Benevolo G, Larocca A, Gentile M, et al. The efficacy and safety of bortezomib and dexamethasone as a maintenance therapy in patients with advanced multiple myeloma who are responsive to salvage bortezomib-containing regimens[J]. Cancer, 2010, 117(9):1884-1890.
31.	Palumbo A, Bringhen S, Rossi D, et al. Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: a randomized controlled trial[J]. J Clin Oncol, 2010, 28(34): 5101-5109.
32.	Uy GL, Goyal SD, Fisher NM, et al. Bortezomib administered pre-auto-SCT and as maintenance therapy post transplant for multiple myeloma: a single institution phase Ⅱ study[J]. Bone Marrow Transplant, 2009, 43(10): 793-800.
33.	Richardson PG, Barlogie B, Berenson J, et al. A phase 2 study of bortezomib in relapsed, refractory myeloma[J]. N Engl J Med, 2003, 348(26): 2609-2617.
34.	Richardson PG, Sonneveld P, Schuster MW, et al. Bortezomib or highdose dexamethasone for relapsed multiple myeloma[J]. N Engl J Med, 2005, 352(24): 2487-2498.
35.	Giuliani N, Morandi F, Tagliaferri S, et al. The proteasome inhibitor bort e zomib affects osteoblast differentiation in vitro and in vivo i n multiple myeloma patients[J]. Blood, 2007, 110(1): 334-338.
36.	Terpos E, Sezer O, Croucher P, et al. Myeloma bone disease and proteasome inhibition therapies[J]. Blood, 2007, 110(4): 1098-1104.
37.	Pineda-Roman M , Zangari M , van Rhee F , et al. VTD combination therapy with bortezomib-thalidomide-dexamethasone is highly effective in advanced and refractory multiple myeloma. Leukemia[J]. 2008, 22(7): 1419-1427.
38.	Palumbo A , Gay F , Bringhen S , Falcone A , et al. Bortezomib, doxorubicin and dexamethasone in advanced multiple myeloma[J]. Ann Oncol, 2008, 19(6): 1160-1165.
39.	Palumbo A , Ambrosini MT , Benevolo G , et al. Bortezomib, melphalan, prednisone, and thalidomide for relapsed multiple myeloma[J]. Blood, 2007, 109(7): 2767-2772.
40.	Richardson P, Jagannath S, Jakubowiak A, et al. Lenalidomide, bortezomib, and dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma (MM): encouraging response rates and tolerability with correlation of outcome and adverse cytogenetics in a phaseⅡ study[J]. ASH Annual Meeting Abstracts, 2008, 112(11): 1742.
41.	Roussou M, Kastritis E, Migkou M, et al. Treatment of patients with multiple myeloma complicated by renal failure with bortezomib-based regimens[J]. Leuk Lymphoma, 2008, 49(5): 890-895. [42] Ludwig H, Drach J, Graf H, et al. Reversal of acute renal failure by bortezomib-based chemotherapy in patients with multiple myeloma[J]. Haematologica, 2007, 92(10): 1411-1414.
42.	Chanan-Khan AA, Kaufman JL, Mehta J, et al. Activity and safety of bortezomib in multiple myeloma patients with advanced renal failu re: a multicenter retrospective study[J]. Blood, 2007, 109(6): 2604-2606. [44] Ludwig H , Adam Z , Hajek R , et al. Light chain-induced acute renal failure can be reversed by bortezomib-doxorubicin-dexamethasone in multiple myeloma: results of a phaseⅡ study[J]. J Clin Oncol , 2010, 28(30): 4635-4641.
43.	Lonial S, Waller EK, Richardson PG, et al. Risk factors and kinetics of thrombocytopenia associated with bortezomib for relapsed, refractory multiple myeloma[J]. Blood, 2005, 106(12): 3777-3784.
44.	Johnston JA, Ward CL, Kopito RR. Aggresomes: a cellular response to misfolded proteins[J]. J Cell Biol, 1998, 143(7): 1883-1898.
45.	Cavaletti G, Gilardini A, Canta A, et al. Bortezomib-induced peripheral neurotoxicity: a neurophysiological and pathological study in the rat[J]. Exp Neurol, 2007, 204(1): 317-325.
46.	Richardson PG, Briemberg H, Jagannath S, et al. Frequency, characteristics, and reversibility f peripheral neuropathy during treatment of advanced multiple myeloma with bortezomib[J]. J Clin Oncol, 2006, 24(19): 3113-3120.
47.	Richardson PG, Sonneveld P, Schuster MW, et al. Reversibility of symptomatic peripheral neuropathy with bortezomib in the phase Ⅲ APEX trial in relapsed multiple myeloma: impact of adose-modifcationguideline[J]. Br J Haematol, 2009, 144(6): 895-903.
48.	Argyriou AA, Iconomou G, Kalofonos HP. Bortezomib-induced peripheral neuropathy in multiple myeloma: a comprehensive review of the literature[J]. Blood, 2008, 112(5): 1593-1599.
49.	何群, 赵谢兰, 贺艳娟, 等. 硼替佐米联合地塞米松治疗多发性骨髓瘤的临床分析[J]. 中南大学学报(医学版), 2010, 35(8): 864-867.
50.	李娟, 赵莹, 罗绍凯, 等. 硼替佐米联合地塞米松治疗24例多发性骨髓瘤的疗效分析[J]. 癌症, 2008, 27(4): 429-434.
51.	刘志刚, 牛挺, 向兵, 等. 硼替佐米为主化疗方案治疗多发性骨髓瘤的临床研究[J]. 四川大学学报(医学版), 2009, 40(2): 358-360.

1. 叶任高, 陆再英. 内科学[M]. 6版. 北京: 人民卫生出版社, 2004: 631.
2. 高玉环, 刘海生. 血液系统恶性肿瘤现代非手术治疗[M]. 北京: 科技文献出版社, 2008: 157-158.
3. 张晓辉, 黄晓军. 造血干细胞移植治疗多发性骨髓瘤的研究进展 [J]. 国际输血及血液学杂志, 2007, 30(4): 328-331.
4. Kenneth CA, Melissa A, William B, et al. NCCN clinical practice guidelines in oncology multiple myeloma version I[S]. 2011: 17.
5. Reeder CB, Reece DE, Kukreti V, et al. Cyclophosphamide, bortezomib and dexamethasone induction for newly diagnosed multiple myeloma: high response rates in a phase Ⅱ clinical trial[J]. Leukemia, 2009, 23(7): 1337-1341.
6. Hideshima T, Miltiades C, Akiyama M, et al. Molecular mechanisms mediating antimyeloma activity of proteasome inhibitor PS-341[J]. Blood, 2003, 101(4): 1530-1534.
7. Jullig M, Zhang WV, Ferreira A, et al. MG132 induced apoptosis is associated with P53-independent induction of pro-apoptotic NOXA and transcriptional activity of beta-catenin [J]. Apoptosis, 2006, 11(4): 627-641.
8. Roccaro AM, Hideshima T, Raje N, et al. Bortezomib mediates antiangi ogenesis in multiple myeloma via direct and indirect effects on endothelia1 cells[J]. Cancer Ras, 2006, 66(1): 184-191.
9. National Comprehensive Cancer Net work (NCCN). NCCN clinical practice guidelines in oncology TM multiple myeloma (V.3.2008).http//www. nccn.org/peofessionals/physician_gle/PDF/myeloma.pdf.
10. National Comprehensive Cancer Net work(NCCN). NCCN clinical practice guidelines in oncology multiple myeloma (V.1.2011). http://www.nccn.org/peofessionals/physician_gle/PDF/myeloma.pdf.
11. Jagannath S, Durie BG, Wolf J, et al. Bortezomib therapy alone and in combination with dexamethasone for previously untreated symptomatic multiple myeloma[J]. Br J Haematol, 2005, 129(6): 776-783.
12. 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[J]. Haematologica, 2006, 91(11): 1498-1505.
13. Harousseau JL , Attal M , Avet-Loiseau H , et al. Bortezomib plus dexamethasone is superior to vincristine plus doxorubicin plus dexamethasone as induction treatment prior to autologous stem-cell transplantation in newly diagnosed multiple myeloma: results of the IFM 2005-01 phase Ⅲ trial[J]. J Clin Oncol, 2010, 28(30): 4621-4629.
14. Corso A , Barbarano L , Mangiacavalli S , et al. Bortezomib plus dexamethasone can improve stem cell collection and overcome the need for additional chemotherapy before autologous transplant in patients with myeloma[J]. Leuk Lymphoma, 2010, 51(2): 236-242.
15. Cavo M, Tacchetti P, Patriarca F, et al. Superior complete response rate and progression-free survival after autologous transplantation with up-front velcade-thalidomide-dexamethasone compared with thalidomide-dexamethasone in newly diagnosed multiple myeloma[J]. Blood, 2008, 112(11): 65.
16. Sonneveld P, van der Holt B, Schmidt-Wolf IGH, et al. First analysis of HOVON-65/GMMG-HD4 randomized phase Ⅲ trial comparing bortezomib, adriamycine, dexamethasone (pad) vs vad as induction treatment prior to high dose melphalan (HDM) in patients with newly diagnosed multiple myeloma (MM)[J]. ASH Annual Meeting Abstracts, 2008, 112(11): 653.
17. Rajkumar SV, Hayman SR,Lacy MQ, et al. Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma[J]. Blood, 2005, 106(13): 4050-4053.
18. Richardson P, Lonial S, Jakubowiak A, et al. Lenalidomide, bortezomib,and dexamethasone in patients with newly diagnosed multiple myeloma:encouraging effcacy in high risk Groups with updated results of a phaseⅠ/Ⅱ study[J]. ASH Annual Meeting Abstracts, 2008,112(11): 92.
19. Corso A , Barbarano L , Mangiacavalli S , et al. Bortezomib plus dexamethasone can improve stem cell collection and overcome the need for additional chemotherapy before autologous transplant in patients with myeloma [J]. Leuk Lymphoma, 2010, 51(2): 236-242.
20. 何东, 刘志刚, 喻琴梅, 等. 硼替佐米提高多发性骨髓瘤干细胞采集的临床研究[J]. 华西医学, 2011, 26(4): 521-523.
21. Chari A, Mazumder M, Jagannath S. Proteasome inhibition and its therapeutic potential in multiple myeloma[J]. Biologics: Targets & Therapy, 2010, 4(10): 273-287.
22. Mateos MV, Richardson PG, Schlag R, et al. Bortezomib plus melphalan and prednisone compared with melphalan and prednisone in previously untreated multiple myeloma: updated follow-up and impact of subsequent therapy in the phase Ⅲ VISTA trial[J]. J Clin Oncol, 2010, 28(13): 2259-2266.
23. Palumbo A, Bringhen S, Rossi D, et al. A prospective, randomized, phase Ⅲ study of bortezomib, melphalan, prednisone and thalidomide (VMPT) versus bortezomib, melphalan and prednisone (VMP) in elderly newly diagnosed myeloma patients[J]. ASH Annual Meeting Abstracts, 2008, 112(11): 652.
24. Rotta M, Storer BE, Sahebi F, et al. Long-term outcomeof patients with multiple myeloma after autologous hematopoietic cell transplantation and nonmyeloablative allografting[J]. Blood, 2009, 113(14): 3383-3391.
25. Mandelli F, Avvisati G, Amadori S, et al. Maintenance treatment with recombinant interferon alfa-2b inpatients with multiple myeloma responding to conventional induction chemotherapy[J]. N Engl J Med,1990, 322(10): 1430-1434.
26. Berenson JR, Crowley JJ, Grogan TM, et al. Maintenance therapy with alternate-day prednisone improves survival in multiple myeloma patients[J]. Blood, 2002, 99(9): 3163-3168.
27. Spencer A, Prince HM, Roberts AW, et al. Consolidation therapy with low-dose thalidomide and prednisolone prolongs the survival of multiple myeloma patients undergoing a single autologous stem-cell transplantation procedure[J]. J Clin Oncol, 2009, 27(11): 1788-1793.
28. Attal M, Harousseau JL, Leyvraz S, et al. Maintenanc therapy with thalidomide improves survival in patients with multiple myeloma[J]. Blood, 2006, 108(10): 3289-3294.
29. Dispenzieri A , Jacobus S , Vesole DH , et al. Primary therapy with single agent bortezomib as induction, maintenance and re-induction in patients with high-risk myeloma: results of the ECOG E2A02 trial[J]. Leukemia , 2010, 24(8): 1406-1411.
30. Benevolo G, Larocca A, Gentile M, et al. The efficacy and safety of bortezomib and dexamethasone as a maintenance therapy in patients with advanced multiple myeloma who are responsive to salvage bortezomib-containing regimens[J]. Cancer, 2010, 117(9):1884-1890.
31. Palumbo A, Bringhen S, Rossi D, et al. Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: a randomized controlled trial[J]. J Clin Oncol, 2010, 28(34): 5101-5109.
32. Uy GL, Goyal SD, Fisher NM, et al. Bortezomib administered pre-auto-SCT and as maintenance therapy post transplant for multiple myeloma: a single institution phase Ⅱ study[J]. Bone Marrow Transplant, 2009, 43(10): 793-800.
33. Richardson PG, Barlogie B, Berenson J, et al. A phase 2 study of bortezomib in relapsed, refractory myeloma[J]. N Engl J Med, 2003, 348(26): 2609-2617.
34. Richardson PG, Sonneveld P, Schuster MW, et al. Bortezomib or highdose dexamethasone for relapsed multiple myeloma[J]. N Engl J Med, 2005, 352(24): 2487-2498.
35. Giuliani N, Morandi F, Tagliaferri S, et al. The proteasome inhibitor bort e zomib affects osteoblast differentiation in vitro and in vivo i n multiple myeloma patients[J]. Blood, 2007, 110(1): 334-338.
36. Terpos E, Sezer O, Croucher P, et al. Myeloma bone disease and proteasome inhibition therapies[J]. Blood, 2007, 110(4): 1098-1104.
37. Pineda-Roman M , Zangari M , van Rhee F , et al. VTD combination therapy with bortezomib-thalidomide-dexamethasone is highly effective in advanced and refractory multiple myeloma. Leukemia[J]. 2008, 22(7): 1419-1427.
38. Palumbo A , Gay F , Bringhen S , Falcone A , et al. Bortezomib, doxorubicin and dexamethasone in advanced multiple myeloma[J]. Ann Oncol, 2008, 19(6): 1160-1165.
39. Palumbo A , Ambrosini MT , Benevolo G , et al. Bortezomib, melphalan, prednisone, and thalidomide for relapsed multiple myeloma[J]. Blood, 2007, 109(7): 2767-2772.
40. Richardson P, Jagannath S, Jakubowiak A, et al. Lenalidomide, bortezomib, and dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma (MM): encouraging response rates and tolerability with correlation of outcome and adverse cytogenetics in a phaseⅡ study[J]. ASH Annual Meeting Abstracts, 2008, 112(11): 1742.
41. Roussou M, Kastritis E, Migkou M, et al. Treatment of patients with multiple myeloma complicated by renal failure with bortezomib-based regimens[J]. Leuk Lymphoma, 2008, 49(5): 890-895. [42] Ludwig H, Drach J, Graf H, et al. Reversal of acute renal failure by bortezomib-based chemotherapy in patients with multiple myeloma[J]. Haematologica, 2007, 92(10): 1411-1414.
42. Chanan-Khan AA, Kaufman JL, Mehta J, et al. Activity and safety of bortezomib in multiple myeloma patients with advanced renal failu re: a multicenter retrospective study[J]. Blood, 2007, 109(6): 2604-2606. [44] Ludwig H , Adam Z , Hajek R , et al. Light chain-induced acute renal failure can be reversed by bortezomib-doxorubicin-dexamethasone in multiple myeloma: results of a phaseⅡ study[J]. J Clin Oncol , 2010, 28(30): 4635-4641.
43. Lonial S, Waller EK, Richardson PG, et al. Risk factors and kinetics of thrombocytopenia associated with bortezomib for relapsed, refractory multiple myeloma[J]. Blood, 2005, 106(12): 3777-3784.
44. Johnston JA, Ward CL, Kopito RR. Aggresomes: a cellular response to misfolded proteins[J]. J Cell Biol, 1998, 143(7): 1883-1898.
45. Cavaletti G, Gilardini A, Canta A, et al. Bortezomib-induced peripheral neurotoxicity: a neurophysiological and pathological study in the rat[J]. Exp Neurol, 2007, 204(1): 317-325.
46. Richardson PG, Briemberg H, Jagannath S, et al. Frequency, characteristics, and reversibility f peripheral neuropathy during treatment of advanced multiple myeloma with bortezomib[J]. J Clin Oncol, 2006, 24(19): 3113-3120.
47. Richardson PG, Sonneveld P, Schuster MW, et al. Reversibility of symptomatic peripheral neuropathy with bortezomib in the phase Ⅲ APEX trial in relapsed multiple myeloma: impact of adose-modifcationguideline[J]. Br J Haematol, 2009, 144(6): 895-903.
48. Argyriou AA, Iconomou G, Kalofonos HP. Bortezomib-induced peripheral neuropathy in multiple myeloma: a comprehensive review of the literature[J]. Blood, 2008, 112(5): 1593-1599.
49. 何群, 赵谢兰, 贺艳娟, 等. 硼替佐米联合地塞米松治疗多发性骨髓瘤的临床分析[J]. 中南大学学报(医学版), 2010, 35(8): 864-867.
50. 李娟, 赵莹, 罗绍凯, 等. 硼替佐米联合地塞米松治疗24例多发性骨髓瘤的疗效分析[J]. 癌症, 2008, 27(4): 429-434.
51. 刘志刚, 牛挺, 向兵, 等. 硼替佐米为主化疗方案治疗多发性骨髓瘤的临床研究[J]. 四川大学学报(医学版), 2009, 40(2): 358-360.

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