改良的以硼替佐米为基础的化疗方案治疗老年复发/难治性多发性骨髓瘤的疗效

目的探讨改良的以硼替佐米为基础的化疗方案(P-CTD方案)对老年复发/难治性多发性骨髓瘤的治疗效果。方法选择44例老年复发/难治性多发性骨髓瘤患者,21例患者接受CTD方案治疗(环磷酰胺、沙利度胺、地塞米松),23例患者接受P-CTD方案(硼替佐米、环磷酰胺、沙利度胺、地塞米松)进行治疗。上述患者共接受4个疗程的治疗,治疗结束后参照国际骨髓瘤工作组(IMWG)制定的多发性骨髓瘤疗效判定标准评估疗效,WHO标准判断不良反应。结果 CTD组患者接受治疗后,完全缓解(CR)和很好的部分缓解(VGPR)3例(14.3%),部分缓解(PR)8例(38.1%),病情稳定(SD)4例(19%),病情进展(PD)6例(28.6%),总有效(CR+VGPR+PR)11例(52.4%)。P-CTD组患者治疗后CR和VGPR 8例(34.8%),PR 11例(47.8%),SD 1例(4.3%),PD 3例(13%),总有效19例(82.6%),P-CTD组缓解率优于CTD组(P<0.05)。两组患者各种不良反应相似(P>0.05)。结论 CTD方案和P-CTD方案均具有良好的安全性,P-CTD方案的缓解率优于CTD方案。     

CMOD方案治疗复发难治性侵袭性非霍奇金淋巴瘤临床观察

目的:评估CMOD方案(米托蒽醌、长春地辛、环磷酰胺及地塞米松)治疗复发及难治性侵袭性非霍奇金淋巴瘤(NHL)的近期疗效及毒副反应。方法:20例复发难治性侵袭性NHL患者行CMOD方案(米托蒽醌10mg d1~3,环磷酰胺650mg/m2 d1,长春地辛4mg d1,地塞米松15mg d1~5)化疗2个疗程,每4~5周重复。2个周期后评价疗效。结果:20例患者中,完全缓解7例,部分缓解6例,疾病稳定4例,疾病进展3例,总有效率为65%。毒副反应主要为骨髓抑制和轻中度的消化道反应。结论:CMOD方案治疗复发难治性侵袭性NHL的近期疗程肯定,毒副反应相对可接受,是一种二线挽救方案。     

硼替佐米为主化疗方案治疗初治与复发难治多发性骨髓瘤近期疗效分析

目的:分析硼替佐米为主化疗方案治疗初治与复发难治多发性骨髓瘤(MM)患者的临床疗效和不良反应.方法:初治MM患者11例,复发、难治MM患者7例均采用VD方案化疗:硼替佐米1.0～1.3 mg/m2第1、4、8和11天快速静脉注射,地塞米松20 mg第1～4天(7例复发难治予地塞米松40 mg)静脉滴注,3周为1疗程,所...     

酞胺哌啶酮联合环磷酰胺及地塞米松治疗难治复发性多发性骨髓瘤疗效观察

目的:评价酞胺哌啶酮(商品名:反应停)联合环磷酰胺及地塞米松治疗难治复发性多发性骨髓瘤(MM)的疗效和不良反应。方法:12例难治复发性MM患者口服酞胺哌啶酮350-400 mg／d,环磷酰胺50 mg／d,地塞米松40 mg／d(第1个月第1-4天,第9-12天,第17-20天,第2个月第1-4天,第9-12天;以后每月服第1-4天)。观察有效率、效应发挥时间、生存时间及不良反应。结果:完全缓解2例,部分缓解3例,进步1例,无效6例,有效率50．0％;效应时间为2-6个月,平均3．5个月;生存时间为8-34个月。不良反应多能耐受,末梢神经炎发生率100％(12／12),窦性心动过缓发生率为50．0％(6／12),便秘为66．7％(8／12),肺栓塞8．3％(1／12),粒细胞减少16．7％(2／12),感染16．7％(2／12)。结论:酞胺哌啶酮联合环磷酰胺及地塞米松治疗难治复发性MM有效,安全,平台期时间长,不良反应较轻。     

硼替佐米为主的联合方案治疗复发或难治性多发性骨髓瘤

目的 观察硼替佐米为主的联合方案治疗复发、难治性多发性骨髓瘤(MM)的疗效和不良反应,探讨应用硼替佐米治疗的最佳方案、剂量及疗程.方法 复发、难治性MM患者46例,均在3～4周的疗程内,给予硼替佐米1.3 mg/m2,1、4、8、11 d,同时联合地塞米松(D)、D+沙立度胺(T)、环磷酰胺(C)+D、米托蒽醌(M)+D、DC+鬼臼乙叉甙(E)+顺铂(P)和DT-P+阿霉素(A)+CE等化疗方案.采用国际骨髓瘤工作组(IMWG)标准判断疗效,并按美国国立癌症研究院不良事件通用命名标准(NCI CTCAE)(第3版)观察不良反应.以接受沙立度胺为基础的联合方案治疗的49例复发、难治MM作历史对照研究.结果 在可评估的43例患者,中位随访时间10个月,31例获得不同程度的缓解,总有效率为72.1%(对照组为51.0%,P＜0.05).其中完全缓解(CR)5例(11.6%),很好的部分缓解(VGPR)12例(27.9%),部分缓解(PR)14例(32.6%).接受1个疗程和2个疗程的总有效率分别为30.2%、58.1%(P＜0.05).常见的不良反应为血小板减少(62.8%)、乏力(55.8%)、恶心(51.2%)及周围神经病变(30.2%)等,但均能耐受.对照组的不良反应有便秘(69.4%)、乏力(59.2%)和头昏、头晕(46.9%)等.结论 硼替佐米为主的联合方案是一种对复发、难治性MM新的治疗选择,疗效优于沙立度胺为基础的联合方案,且两者毒性谱有所不同.     

硼替佐米联合VAD方案治疗多发性骨髓瘤

目的：观察硼替佐米联合VAD方案治疗初治、难治复发多发性骨髓瘤（MM）患者的疗效及安全性。方法：15例初治及难治复发MM患者,硼替佐米1.3mg/m2,d1、4、8、11或d0、3、7、10静脉注射,每28d1个疗程;每个疗程联合VAD方案化疗,每位患者接受2-6个疗程治疗。采用2006年MM国际统一疗效标准观察疗效,并按NCI/PNIH标准判断不良反应。结果：中位随访14个月,治疗总有效率80%,其中8例患者达完全缓解,1例患者达良好的部分缓解,3例患者达部分缓解,2例患者疾病无进展,1例患者治疗过程中疾病进展。最常见的不良反应包括胃肠道症状,不同程度的白细胞、血小板减少,周围神经病和乏力等,经对症治疗及调整用药剂量后均能改善。结论：硼替佐米联合VAD方案可提高MM患者治疗完全缓解率,并未增加周围神经毒性。     

硼替佐米联合化疗治疗10例多发性骨髓瘤

目的:观察硼替佐米联合化疗药物治疗初治、复发难治多发性骨髓瘤(MM)的疗效及安全性。方法:5例初治MM患者在每一疗程的第1、4、8、11天静脉注射硼替佐米0.7～1.3mg/m2,每3周为一疗程;每2个疗程(6周)的第1～4天,口服美法仑9mg/(m2·d)和泼尼松60mg/(m2·d);每例患者至少接受2～10个疗程。5例复发难治患者,在每3周1个疗程,第1、8天分别静脉注射硼替佐米3.5mg,或第1、4、8、11天1.0～1.3mg/m2。每次用硼替佐米前静脉注射地塞米松40mg;每例患者至少接受1～6个疗程。采用Blade标准评价疗效,按照美国国立癌症研究所(NCI)(第3版)判断不良反应。结果:中位随访8个月,5例初治患者中2例完全缓解(CR),1例接近完全缓解(nCR),1例部分缓解(PR),1例轻微反应(MR)。5例复发难治患者中,2例nCR,2例MR,1例无改变(NC)。主要不良反应包括胃肠道症状、不同程度的血小板减少、周围神经症状和乏力等。经对症治疗及调整用药剂量后均能改善。结论:硼替佐米对于初治或复发难治的MM患者,是一种可以耐受的、疗效确切的新的治疗选择。     

硼替佐米及沙利度胺联合VAD方案治疗难治复发性多发性骨髓瘤疗效观察

目的:观察硼替佐米、沙利度胺联合VAD方案治疗难治复发性多发性骨髓瘤(MM)的临床疗效和不良反应。方法:9例难治复发性MM患者均采用硼替佐米、沙利度胺联合VAD方案治疗。其中,长春新碱0.4mg/d,d1～4;阿霉素10mg/d,d1～4;地塞米松40mg/次,d1～4,d9～12,d17～20;硼替佐米2mg/d,d1,4,8,11;沙利度胺,起始量100mg/d,根据患者情况,逐渐加量至200mg/d,每晚顿服,治疗2个周期。观察疗效,并按WHO不良反应分级标准判断不良反应。结果:9例患者,3例完全缓解/接近完全缓解(CR/nCR),4例部分缓解(PR),1例进步,1例无效,CR加PR率达77.8%,总有效率88.9%。不良反应主要有乏力、便秘、皮疹、胃肠道反应及末梢神经炎,均可耐受。结论:硼替佐米、沙利度胺联合VAD方案治疗难治复发性MM近期疗效显著,耐受性好,是一种新的治疗选择。     

地塞米松联合沙立度胺治疗多发性骨髓瘤临床观察

目的:观察大剂量地塞米松联合低剂量沙立度胺治疗多发性骨髓瘤的临床疗效.方法:10例多发性骨髓瘤患者,包括3例髓外浆细胞瘤患者.其中沙立度胺剂量50～200 mg/d口服,同时联合大剂量地塞米松40 mg静脉滴注,连续4 d,间隙5 d,治疗3个月.结果:完全缓解(CR)2例,部分缓解(PR)2例,进步2例,无效4例,其中3例为髓外浆细胞瘤患者;不良反应可耐受,轻度便秘多见.结论:大剂量地塞米松联合低剂量沙立度胺治疗多发性骨髓瘤短期内安全有效,而对髓外浆细胞瘤患者效果不佳.     

持续小剂量地塞米松加沙立度胺治疗难治性多发性骨髓瘤的临床疗效观察

目的:观察持续小剂量地塞米松加沙立度胺对难治性多发性骨髓瘤的疗效.方法:持续小剂量地塞米松加沙立度胺治疗难治性多发性骨髓瘤21例,治疗方法用沙立度胺初始剂量100～200 mg/d,晚上1次顿服,从100 mg开始的患者过2周后加量至200 mg,以后维持在200 mg,地塞米松给予1.5 mg,每天2次口服,二药联合小剂量应用,持续3个月,在后1个半月,地塞米松可减量至1.5 mg,每天1次.3个月后进行化疗1个疗程,3个月为1个周期.结果:2个周期治疗后有6例部分缓解,9例进步,6例无效,其中3例加重,总有效率达71.4%.结论:持续小剂量地塞米松加沙立度胺治疗难治性多发性骨髓瘤疗效确切,不良反应少.     

Low-dose thalidomide regimens in therapy of relapsed or refractory multiple myeloma

Thalidomide has been estimated as a useful drug in therapy of refractory or relapsed multiple myeloma. Recently, several studies have shown very good results in therapy combination of thalidomide, cyclophosphamide and dexamethasone, but still high doses of thalidomide associated with serious adverse events have been used. In our study, we performed low-dose thalidomide regimens; the aim of this study was to verify the effect and to assess their toxicity. For younger patients up to 65 years we used a "CTD-junior" regimen, consisting of oral thalidomide 200 mg daily, pulsed intravenous cyclophosphamide 800 mg on day 1 and pulsed oral dexamethasone 40 mg on days 1-4 and 12-15, for every three weeks. For patients over 65 years, the "CTDsenior" regimen was used, with oral thalidomide 50-100 mg daily (according to tolerability), oral cyclophosphamide 50 mg daily and pulsed dexamethasone 20 mg on days 1-4 and 15-18, for every four weeks. From the group of 97 patients with progressive form of multiple myeloma or with resistance to conventional chemotherapy, 85 patients were evaluated. According to the EBMT criteria, we observed in 8% complete remission (CR), in 50% partial response (PR) and in 22% minimal response (MR). Ten patients (12%) were stabilized and seven patients (8%) progressed. Toxicity of both regimens was mild and well manageable, when weakness, obstipation, neuropathy of lower extremities, glycoregulation worsening and mild leucopenia occurred most often. These results showed that low doses of thalidomide are still effective, when combined with other drugs. Both CTD regimens are safe also for patients with advanced and heavily pretreated multiple myeloma.     

The combination of thalidomide and intermediate-dose dexamethasone is an effective but toxic treatment for patients with primary amyloidosis (AL)

Based on the efficacy of thalidomide in multiple myeloma and on its synergy with dexamethasone on myeloma plasma cells, we evaluated the combination of thalidomide (100 mg/d, with 100-mg increments every 2 weeks, up to 400 mg) and dexamethasone (20 mg on days 1-4) every 21 days in 31 patients with primary amyloidosis (AL) whose disease was refractory to or had relapsed after first-line therapy. Eleven (35%) patients tolerated the 400 mg/d thalidomide dose. Overall, 15 (48%) patients achieved hematologic response, with 6 (19%) complete remissions and 8 (26%) organ responses. Median time to response was 3.6 months (range, 2.5-8.0 months). Treatment-related toxicity was frequent (65%), and symptomatic bradycardia was a common (26%) adverse reaction. The combination of thalidomide and dexamethasone is rapidly effective and may represent a valuable second-line treatment for AL.     

Clinical efficacy of a bortezomib, cyclophosphamide, thalidomide, and dexamethasone (Vel-CTD) regimen in patients with relapsed or refractory multiple myeloma: a phase II study

The clinical efficacy and safety of a four-drug combination of bortezomib, cyclophosphamide, thalidomide, and dexamethasone was assessed for patients with relapsed or refractory multiple myeloma. Seventy patients received at least two cycles of treatment with bortezomib 1.3 mg/m² intravenously on days 1, 4, 8, and 11; cyclophosphamide 150 mg/m² orally on days 1–4; thalidomide 50 mg/day orally every day; and dexamethasone 20 mg/m² intravenously on days 1, 4, 8, and 11. The overall best response rate was 88%, with 46% complete response, 9% very good partial response, and 33% partial response. After a median follow-up of 12.6 months, the median progression-free survival (PFS) was 14.6 months with a 3-year PFS of 14% and the median overall survival (OS) was 31.6 months with a 3-year OS of 47%. Grade 3 or 4 adverse events included thrombocytopenia (12%), neutropenia (4%), peripheral sensory neuropathy (3%), with thrombosis being very rare (<1%). Bortezomib combined with cyclophosphamide, thalidomide, and dexamethasone is a highly effective salvage therapy with manageable toxicity for patients with relapsed or refractory multiple myeloma.     

Combination Therapy with Thalidomide,Incadronate, and Dexamethasone for Relapsed or Refractory Multiple Myeloma

The feasibility and efficacy of a combination of thalidomide, incadronate, and dexamethasone (TID) were studied in 12 patients with relapsed or refractory multiple myeloma. The protocol, consisting of 300 mg/day of thalidomide administered orally, intravenous incadronate (10 mg/day) administered weekly, and 12 mg/day dexamethasone for 4 days, was repeated every 3 weeks. Evaluations of efficacy and toxicity were carried out every 3 weeks and were continued for 3 cycles. Three patients were excluded during the study because of apnea, severe somnolence, and pancytopenia. Of 9 evaluated patients, the partial responses achieved in 3 patients and the minor responses achieved in 4 patients corresponded to a response rate of 78% according to the criteria of the European Group for Blood and Marrow Transplantation. In addition, painful osteolytic symptoms improved rapidly after 1 cycle of TID therapy in the 10 patients evaluated. These data suggest that TID is a feasible and promising therapeutic approach for refractory and relapsed multiple myeloma.     

A phase 2 study of two doses of bortezomib in relapsed or refractory myeloma

In a phase 2 open-label study of the novel proteasome inhibitor bortezomib, 54 patients with multiple myeloma who had relapsed after or were refractory to frontline therapy were randomized to receive intravenous 1.0 or 1.3 mg/m(2) bortezomib twice weekly for 2 weeks, every 3 weeks for a maximum of eight cycles. Dexamethasone was permitted in patients with progressive or stable disease after two or four cycles respectively. Responses were determined using modified European Group for Blood and Marrow Transplantation criteria. The complete response (CR) + partial response (PR) rate for bortezomib alone was 30% [90% confidence interval (CI), 15.7-47.1] and 38% (90% CI, 22.6-56.4) in the 1.0 mg/m(2) (8 of 27 patients) and 1.3 mg/m(2) (10 of 26 patients) groups respectively. The CR + PR rate for patients who received bortezomib alone or in combination with dexamethasone was 37% and 50% for the 1.0 and 1.3 mg/m(2) cohorts respectively. The most common grade 3 adverse events were thrombocytopenia (24%), neutropenia (17%), lymphopenia (11%) and peripheral neuropathy (9%). Grade 4 events were observed in 9% (five of 54 patients). Bortezomib alone or in combination with dexamethasone demonstrated therapeutic activity in patients with multiple myeloma who relapsed after frontline therapy.     

Oral Melphalan,Dexamethasone, and Thalidomide for the Treatment of Refractory Multiple Myeloma

We present a patient with refractory multiple myeloma who showed a good response to a combination therapy with oral melphalan, dexamethasone, and thalidomide (MDT). A 48-year-old woman with myeloma refractory to thalidomide, dexamethasone, and clarithromycin received 6 mg melphalan for 4 days every 6 weeks in combination with thalidomide (100 mg daily) and dexamethasone (5 mg daily for 2 days every week). Four months after the initiation of MDT therapy, a 78% reduction of monoclonal protein was achieved. Although the efficacy of oral MDT combination therapy in elderly patients with newly diagnosed myeloma has been reported, the present data demonstrate the effectiveness of MDT therapy for refractory myeloma and warrant further exploration with this MDT regimen to treat myeloma.     

Intravenous melphalan, thalidomide and prednisone in refractory and relapsed multiple myeloma

OBJECTIVES: Thalidomide combined with conventional chemotherapies including oral melphalan shows significant anti-myeloma activity. To address this issue, feasibility and efficacy of a three drug combination consisting of intravenous (i.v.) melphalan, thalidomide and prednisone [M(i.v.)PT] was evaluated in advanced myeloma patients. PATIENTS AND METHODS: Twenty-four advanced myeloma patients were treated with multiple cycles of a regimen consisting of low dose i.v. melphalan (20 mg/m2) at d 1, thalidomide at the dose of 50-100 mg/d given continuously and oral prednisone at the planned dose of 50 mg/d every other day. Intravenous melphalan was administered every fourth month. Median time from diagnosis was 40 months (range: 8-144 months). Fifteen patients (66%) had previously been treated with a combination of thalidomide and dexamethasone or with thalidomide alone. RESULTS: Overall, on an intent-to treat basis, 14 patients responded: three achieved near complete remission (nCR), seven achieved partial response (PR), four minimal response (MR). Six patients showed stable disease (SD) and four-disease progression. Interestingly, of five patients who had previously progressed while on thalidomide and prednisone, one reached nCR, two PR and one MR. After a median follow up of 14 months, median progression free survival was 9 months. Response duration was longer than that induced by the previous line of treatment in eight patients (33%). Thalidomide-associated toxicity mainly consisted of constipation, tingling and sedation. CONCLUSIONS: M(i.v.)PT is an effective regimen, which can overcome resistance to thalidomide plus prednisone in advanced myeloma with acceptable toxicity.     

Combined bendamustine, prednisolone and thalidomide for refractory or relapsed multiple myeloma after autologous stem-cell transplantation or conventional chemotherapy: results of a Phase I clinical trial

Thalidomide is an effective agent for advanced refractory or relapsed multiple myeloma (MM), although dose-limiting toxicity (DLT) may limit its use. This Phase I study found that a combination of low-dose thalidomide with bendamustine and prednisolone (BPT) maintained or increased efficacy, whilst avoiding DLT in 28 patients with MM that was refractory or that had relapsed after conventional chemotherapy or high-dose therapy with stem-cell support. BPT comprised fixed doses of bendamustine (60 mg/m(2)) and prednisolone (100 mg), and escalating doses of thalidomide (50, 100, 200 mg). Treatment cycles were repeated every 28 d until the occurrence of maximum response, DLT, or disease progression. Twenty-four patients responded after at least two cycles (four complete remission, six very good partial remission, 14 partial remission). Median progression-free and overall survival for all patients was 11 and 19 months respectively. Only mild/moderate non-haematological side effects were observed and no patient developed dose-limiting haematotoxicity. Transient grade 3-4 neutropenia was reported in 12 patients, and grade 3-4 thrombocytopenia occurred in two patients. We conclude that BPT therapy was well tolerated in patients with relapsed or refractory MM, with a response rate higher than 80%. The maximum tolerated dose of thalidomide was not reached in this study.