Faculty of Medicine, UBC Hospital, 2211 Wesbrook Mall, University of British Columbia, Vancouver, BC, V6T 2B5 Canada.
Neurology. 2010 Jun 1;74(22):1822-6. doi: 10.1212/WNL.0b013e3181e0f7e6. Epub 2010 Apr 28.
Mitoxantrone is used for aggressive multiple sclerosis (MS), but concerns about safety, including cardiotoxicity and other laboratory measures, prevail.
To evaluate the incidence and potential predictors of adverse events associated with mitoxantrone at the MS Clinic, University of British Columbia, Canada.
Retrospective review of patients treated with mitoxantrone by standard protocol; maximum cumulative dose = 120 mg/m(2). Left ventricular ejection fraction (LVEF) was measured with regular multiple-gated acquisition (MUGA) scans; blood cell counts and biochemical liver tests were performed before infusions. Generalized estimating equations were used to examine potential predictors of adverse events (graded according to the Common Toxicity Criteria, version 4) in patients with normal baseline and > or =1 follow-up MUGA or laboratory assessment.
All 163 patients (58% women) treated with mitoxantrone from 1999 to 2007 were reviewed. Mean baseline age was 41.9 (SD 10.8) years, cumulative dose was 59.7 (SD 26.0) mg/m(2), and median follow-up duration was 14 months (maximum 6.5 years). By study end, 14% developed de novo cardiotoxicity (grade > or =2) as measured by decreased LVEF, 27% neutropenia (grade > or =1), 15% anemia (grade > or =1), and 15% liver toxicity (grade > or =1). Possible predictors of adverse events included sex, age, disease duration, and cumulative dose; only women exposed to a higher cumulative dose were at a greater risk of anemia (adjusted odds ratio 1.26, 95% confidence interval 1.08-1.48 per 10 mg/m(2)).
Based on cardiac and laboratory assessments, mitoxantrone was reasonably well tolerated. However, cardiotoxicity was evident after doses well below current maximum recommended levels. A dose-response effect was not apparent. Findings emphasize the importance of monitoring; the long-term effects of mitoxantrone in multiple sclerosis require investigation.
米托蒽醌用于侵袭性多发性硬化症（MS），但对安全性的担忧，包括心脏毒性和其他实验室指标，仍然存在。
评估加拿大不列颠哥伦比亚大学多发性硬化症诊所中使用米托蒽醌治疗相关的不良事件的发生率和潜在预测因素。
回顾性分析按照标准方案接受米托蒽醌治疗的患者；最大累积剂量=120mg/m2。左心室射血分数（LVEF）通过定期使用多门控采集（MUGA）扫描进行测量；在输注前进行血细胞计数和生化肝功能检查。使用广义估计方程来检查基线正常且>或=1次后续 MUGA 或实验室评估的患者中不良事件（根据通用毒性标准，第 4 版进行分级）的潜在预测因素。
回顾了 1999 年至 2007 年期间接受米托蒽醌治疗的 163 例患者（58%为女性）。平均基线年龄为 41.9（SD 10.8）岁，累积剂量为 59.7（SD 26.0）mg/m2，中位随访时间为 14 个月（最长 6.5 年）。研究结束时，14%的患者发生了新的心脏毒性（LVEF 降低，等级>或=2），27%的患者发生了中性粒细胞减少症（等级>或=1），15%的患者发生了贫血症（等级>或=1），15%的患者发生了肝功能毒性（等级>或=1）。不良事件的可能预测因素包括性别、年龄、疾病持续时间和累积剂量；只有接受更高累积剂量的女性发生贫血的风险更高（调整后的优势比为 1.26，95%置信区间为每 10mg/m2 1.08-1.48）。
基于心脏和实验室评估，米托蒽醌具有良好的耐受性。然而，在剂量远低于当前最大推荐水平的情况下，就已经出现了心脏毒性。没有出现剂量反应效应。这些发现强调了监测的重要性；米托蒽醌在多发性硬化症中的长期影响需要进一步研究。
