补肾活血通络方联合改良PD方案诱导治疗初治多发性骨髓瘤疗效观察
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摘要
目的:观察自拟补肾活血通络方联合改良PD(硼替佐米+地塞米松)方案诱导治疗初治多发性骨髓瘤(MM)的疗效及安全性。方法:回顾性分析2013年1月-2017年12月山东中医药大学附属医院初诊多发性骨髓瘤患者32例,均给予补肾活血通络方联合改良PD方案诱导治疗:硼替佐米1. 3 mg/m~2,皮下注射,d1,8,15,22;地塞米松20mg/d,d1～2,8～9,15～16,22～23。每5周为1个疗程。所有纳入患者接受4个疗程的治疗后评价疗效。采用国际骨髓瘤工作组(International Myeloma Working Group,IMWG)的疗效标准判断疗效。结果:所有患者接受诱导治疗后,达到部分缓解(PR)以上疗效93. 75%,其中完全缓解(Complete response,CR) 6例(18. 75%)、非常好的部分缓解(Very good partial response,VGPR) 18例(56. 25%)、部分缓解(PR) 6例(18. 75%)、疾病稳定(Stable disease,SD) 2例(6. 25%)。发生周围神经病变1级4例(12. 5%)。结论:补肾活血通络方联合改良PD方案诱导治疗初治多发性骨髓瘤是非常安全高效的方案,该方案治疗过程中周围神经病变等并发症发生率较低。
Objective: To investigate the efficacy of bortezomib combined with dexamethasone( PD) and Kidney-Reinforcing and Blood Circulation-Activating and Dredging Collaterals Decoction for the initial treatment of multiple myeloma( MM). Methods: Thirty-two patients with MM who were hospitalized in The Affiliated Hospital of Shandong University of Traditional Chinese Medicine from January 2013 to December 2017 were treated with bortezomib combined with dexamethasone( PD) and Kidney-Reinforcing and Blood Circulation-Activating and Dredging Collaterals Decoction. The bortezomib combined with dexamethasone( PD) : bortezomib 1. 3 mg/m~2 by subcutaneous injection,d1,8,15,22 and dexamethasone 20 mg/d,d1-2,d8-9,d15-16,d22-23,with 5 weeks as one course. The efficacy was evaluated after 4 courses of treatment. The International Myeloma Working Group( The International Myeloma Working Group,IMWG) of the standard treatment was used to evaluate the curative effect. Results: After treatment,partial response( PR) curative effect was 93. 75%,including complete response( CR) in 6 cases( 18.75%),very good partial response( VGPR) 18 cases( 56. 25%) and partial response( PR) 6( 18. 75%),stable disease( SD) in2 cases( 6. 25%). There were 4 cases of peripheral neuropathy( 12. 5%). Conclusion: Kidney-Reinforcing and Blood Circulation-Activating and Dredging Collaterals Decoction and PD solutions are very safe and effective in the treatment of multiple myeloma. The incidence of peripheral neuropathy complications such as in the process of solution treatment is relatively low.
Objective: To investigate the efficacy of bortezomib combined with dexamethasone( PD) and Kidney-Reinforcing and Blood Circulation-Activating and Dredging Collaterals Decoction for the initial treatment of multiple myeloma( MM). Methods: Thirty-two patients with MM who were hospitalized in The Affiliated Hospital of Shandong University of Traditional Chinese Medicine from January 2013 to December 2017 were treated with bortezomib combined with dexamethasone( PD) and Kidney-Reinforcing and Blood Circulation-Activating and Dredging Collaterals Decoction. The bortezomib combined with dexamethasone( PD) : bortezomib 1. 3 mg/m~2 by subcutaneous injection,d1,8,15,22 and dexamethasone 20 mg/d,d1-2,d8-9,d15-16,d22-23,with 5 weeks as one course. The efficacy was evaluated after 4 courses of treatment. The International Myeloma Working Group( The International Myeloma Working Group,IMWG) of the standard treatment was used to evaluate the curative effect. Results: After treatment,partial response( PR) curative effect was 93. 75%,including complete response( CR) in 6 cases( 18.75%),very good partial response( VGPR) 18 cases( 56. 25%) and partial response( PR) 6( 18. 75%),stable disease( SD) in2 cases( 6. 25%). There were 4 cases of peripheral neuropathy( 12. 5%). Conclusion: Kidney-Reinforcing and Blood Circulation-Activating and Dredging Collaterals Decoction and PD solutions are very safe and effective in the treatment of multiple myeloma. The incidence of peripheral neuropathy complications such as in the process of solution treatment is relatively low.
引文
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[24]刘小君,程琼,丁斐.牛膝提取物神经再生素促小鼠坐骨神经再生的实验研究[J].时珍国医国药,2009,20(1):16-18.
[25]王法,黄耀添,殷琦,等.甘露醇和当归对周围神经再灌注损伤的保护作用[J].中华显微外科杂志,1999,8(22):40-42.
[2]Petrucci MT,Giraldo P,Corradini P,et al.A Prospective,international phase 2 study of bortezomib retreatment in patients with relapsed multiple myelome[J].Br J Haematol,2013,160(5):649-659.
[3]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.
[4]中国医师协会血液科分会多发性骨髓瘤专业委员会.多发性骨髓瘤周围神经病变诊疗中国专家共识(2015年)[J].中华内科学杂志,2015,54(9):821-824
[5]张之南,沈梯.血液病诊断及疗效标准[M].3版.北京:科学出版社,2008:232.
[6]黄振翘,梁冰,陈信义,等.实用中医血液病学[M].上海:上海科学技术出版社,2005:471.
[7]Gaballa MR,Laubach JP,Schlossman RL,et al.Management of myeloma-associated renal dysfunction in the era of novel therapies[J].Expert Rev Hematol,2012,59(1):51-68.
[8]Palumbo A,Rajkumar SV,San Miguel JF,et al.Internationl Myeloma Working Group consensus statement for the management,treatment,and supportive care of patients with myeloma not eligible for standard autologous stem-cell transplantation[J].J Clin Oncol,2014,32(6):587-600
[9]U.S.Department of Health and Human Services,National Institutes of Health,National Cancer Institute.Common Terminology Criteria for Adverse Events(CTCAE)v4.0[EB/OL].2009(2010-06-14)[2015-06-09].http://evs.nci.nih.gov/ftpl/CTCAE/About.html.
[10]Nooka AK,Kaufman JL,Behera M,et al.Bortezomib-containing induction regimens in transplant-eligible myeloma patients:a metaanalysis of phase 3 randomized clinical trials[J].Cancer,2013,119(23):4119-4128.
[11]Hideshima T,Richardson P,Chanhan D,et al.The proteasome inhibitor PS-341 inhibits growth,induces apoptosis and overcome drug resistance in human multiple myeloma cell[J].Cancer Res,2001,61(7):3071-3076
[12]Jaqannath S,Richardson PG,Barlogie B,et al.Bortezomib in combination with dexamethasone for the treatment of patients with relapsed and/or refractory multiple myeloma with less than optimal response to bortezomib alone[J].Haematologica,2006,91(7):929-934.
[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-O1 phaseⅢtrial[J].J Clin Oncol,2010,28(30):4621-4629.
[14]刘宇,武操,史克倩.四种治疗多发性骨髓瘤方案的疗效评价[J].中国新药与临床杂志,2014,33(10):756-759.
[15]Kropff MH,Bisping G,Wenning D,et al.Bortezomib in combination with dexamethasone for relapsed multiple myeloma[J].Leuk Res,2005,29(5):587-590.
[16]Moreau P,Hulin C,Macro M,et al.VTD is superior to VCD prior to intensive therapy in multiple myeloma:results of the prospective IFM2013-04 trial[J].Blood,2016,127(21):2569-2574.
[17]Delforge M,BladéJ,Dimopoulos MA,et al.Treatment-related peripheral neuropathy in multiple myeloma:the challenge continues[J].Lancet Oncol,2010,11(11):1086-1095
[18]Dimopoulos MA,Mateos MV,Richardson PG,et al.Risk factors for,and reversibility of,peripheral neuropathy associated with bortezomib-melphalan-prednisone in newly diagnosed patients with multiple myeloma:subanalysis of the phase 3 VISTA study[J].Eur J Haematol,2011,86(1):23-31.
[19]Richardson PG,Xie W,Mitsiades C,et al.Single-agent bortezomib in previously untreated multiple myelome:efficacy,characterization of peripheral neuropathy,and molecular correlation with response and neuropathy[J].J Clin Oncol,2009,27(21):3518-3525.
[20]Pantani L,Zamagni E,Zannetti B A,et al.Bortezomib and dexamethasone as salvage therapy in patients with relapsed/refractory multiple myeloma:analysis of long-term clinical outcomes[J].Ann Hemato1,2014,93(1):123-128.
[21]Bringhen S,Larocca A,Rossi D,et al.Efficacy and safety of onceweekly bortezomib in multiple myeloma patients[J].Blood,2010,116(23):4745-4753.
[22]Moreau P,Pylypenko H,Grosicki S,et al.Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma:a randomised,phase 3,non-inferiority study[J].Lancet Oncol,2011,12(5):431-440.
[23]Kumar S,Flinn I,Richardson PG,et al.Randomized,multicenter,phase 2 study(EVOLUTION)of combinations of bortezomib,dexamethasone,cyclophosphamide,and lenalidomide in previously untreated multiple myeloma[J].Blood,2012,119(19):4375-4382.
[24]刘小君,程琼,丁斐.牛膝提取物神经再生素促小鼠坐骨神经再生的实验研究[J].时珍国医国药,2009,20(1):16-18.
[25]王法,黄耀添,殷琦,等.甘露醇和当归对周围神经再灌注损伤的保护作用[J].中华显微外科杂志,1999,8(22):40-42.