...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Current therapeutic research, clinical and experimental. >Mitoxantrone in worsening secondary progressive multiple sclerosis: A prospective, open-label study
【24h】

Mitoxantrone in worsening secondary progressive multiple sclerosis: A prospective, open-label study

机译：米托蒽醌在继发性进行性多发性硬化恶化中的作用：一项前瞻性开放标签研究

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

An antineoplastic agent, mitoxantrone (MX) is used to treat neurologic disability and/or reduce the frequency of clinical relapses in patients with secondary progressive, progressive relapsing, or worsening relapsing-remitting multiple sclerosis (MS).Based on a MEDLINE search for literature concerning the use of IV MX in patients with secondary progressive MS (SPMS), there is a paucity of data to identify the clinical characteristics of responders.The aim of this study was to monitor the effects of IV MX in patients with SPMS and varied clinical characteristics whose condition continued to worsen despite receiving IV methylprednisolone treatment.This prospective,open-label study was conducted at the Multiple Sclerosis Clinic,Center for Neurologic Disorders, Milwaukee, Wisconsin.Male and female patients aged ≥18 years with SPMS whose neurologic condition, as assessed using routine neurologic examination, worsened despite at least one 5-day course of IV methylprednisolone treatment (1g/d) were enrolled.Patients received premedication with an antiemetic and IV MX 12 mg/m2 every 12 weeks for up to 2 years, with a total cumulative dose not to exceed 96 mg/m2.All patients were followed up for 1 year after treatment cessation. Efficacy was assessed at baseline, end of treatment, and 1-year follow-up using the Extended Disability Status Scale (EDSS) (which measures the functional disability level) (0=normal findings on neurologic examination to 10 = death from MS complications). Tolerability was assessed before, during, and immediately after each infusion and at 2 weeks after each infusion, using direct questioning of, and spontaneous reporting by, the patients; physical examination; and laboratory assessments. Cardiac multigated acquisition scanning was performed at baseline and every 24 weeks during the treatment period.Forty-eight patients were enrolled (28 women, 20 men; mean [SD] age, 47.6 [8.6] years; mean [SD] disease duration, 12.5 [6.0] years; mean [SD] baseline EDSS score, 6.9 [1.2]).Twenty-three patients completed the entire course of treatment;the remaining 25 were withdrawn after 1 year of treatment due to lack of efficacy (22 patients), asymptomatic cardiac ejection fraction <40% (2), and severe septicemia and worsening of MS requiring extended respiratory support and hospitalization (1). Patients who completed only 1 year of treatment were younger compared with those who completed 2 years (mean age, 45.2 vs 50.1 years; P < 0.05). No significant change in mean EDSS score was found at the end of treatment or at 1-year posttreatment follow-up. In patients whose disability improved by 2–0.5 on the EDSS (11 patients at 1 year; 5 patients at 2 years), the degree of improvement noted at 1-year follow-up in patients with a baseline EDSS score 3.0 to 5.5 versus 6.0 to 7.5 and 8.0 to 9.0 was significant (both, P < 0.05). Severe adverse effects occurred in 14.6% of patients and included marked leukopenia (peripheral white blood cell count, <100 cells/μL) with urosepsis, requiring hospitalization in 7 patients, 1 of whom developed severe septicemia and worsening of MS, requiring >4 weeks of respiratory support. Cardiac ejection fraction decreased to <40% in 2 patients after 1 year of treatment (total dose, 48 mg/m2). These 2 patients were asymptomatic, but the investigators decided to discontinue treatment. Cardiac function returned to normal range (but not to near-baseline levels) within 12 weeks after treatment cessation. Although all patients were premedicated with antiemetics, 10 (20.8%) reported mild nausea (treated with repeat administration of antiemetics), and 2 of 16 (12.5%) premenopausal patients reported slightly increased bleeding during menstruation after l year of IV MX therapy, requiring no medical therapy or adjustment in the treatment protocol.Based on the results of this study in this small group of patients with worsening SPMS, IV MX treatment for up to 2 years was not associated with a significant change in EDSS
机译：抗肿瘤药米托蒽醌（MX）用于治疗继发进行性，进行性复发或恶化为复发-缓解型多发性硬化症（MS）的患者的神经系统残疾和/或减少其临床复发的频率。关于在继发性进行性MS（SPMS）患者中使用IV MX的资料很少，无法确定应答者的临床特征。本研究的目的是监测IV MX在SPMS患者和各种临床中的作用该特征是在接受威斯康辛州密尔沃基市神经病学中心神经硬化中心的多发性硬化诊所进行的一项前瞻性，开放标签研究中进行的，该患者的年龄≥18岁，患有SPMS的神经系统疾病，使用常规神经系统检查评估得出，尽管至少进行了5天的静脉注射甲基强的松龙疗程（1g / d患者每12周接受一次止吐和IV MX 12 mg / m2的处方药，为期2年，总累积剂量不超过96 mg / m2。所有患者在治疗终止后均接受随访1年。 。在基线，治疗结束和1年随访中使用扩展的残疾状态量表（EDSS）（评估功能性残疾水平）评估疗效（0 =神经系统检查的正常结果至10 = MS并发症导致的死亡） 。通过直接询问患者并自发报告，在每次输注之前，期间和之后以及每次输注后2周评估耐受性。身体检查;和实验室评估。在治疗期间的基线和每24周进行心脏多路采集扫描。招募了48位患者（28名女性，20名男性;平均[SD]年龄，47.6 [8.6]岁;平均[SD]病程，12.5） [6.0]年;平均[SD] EDSS基线平均分，为6.9 [1.2]。23位患者完成了整个疗程;其余25位患者由于缺乏疗效而在1年后退出治疗（22位患者），无症状的心脏射血分数<40％（2），严重的败血病和MS恶化需要延长的呼吸支持和住院治疗（1）。仅完成1年治疗的患者比完成2年的患者年轻（平均年龄，分别为45.2和50.1岁; P <0.05）。在治疗结束或治疗后1年的随访中，未发现EDSS平均评分有明显变化。在EDSS上残疾改善了2-0.5的患者中（1年时11例; 2年时5例），基线EDSS评分为3.0至5.5与6.0的患者在1年随访中发现了改善程度分别为7.5和8.0到9.0（P均<0.05）。严重不良反应发生在14.6％的患者中，包括明显的白细胞减少症（外周白细胞计数，<100个细胞/μL）和尿道炎，需要住院治疗的7名患者中，其中1名出现严重的败血病和MS恶化，需要4周以上的时间呼吸支持。治疗1年后2例患者的心脏射血分数降低至<40％（总剂量48 mg / m2）。这2例患者无症状，但研究者决定终止治疗。停止治疗后12周内，心脏功能恢复到正常范围（但未恢复到接近基线水平）。尽管所有患者均接受过止吐药的治疗，但10例（20.8％）报告为轻度恶心（反复服用止吐药治疗），而16例绝经前患者中的2例（12.5％）在经IV MX治疗后月经期间出血略有增加，需要根据这项研究的结果，在这小部分SPMS恶化的患者中，IV MX治疗长达2年与EDSS的显着改变无关

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号