Definitions of breakthrough disease and second-line agents

Conventional disease-modifying agents are only moderately effective, so breakthrough disease activity is commonly seen. The evidence from randomized clinical trials and real-world observational data supporting the use of the second-line agents natalizumab, mitoxantrone, and cyclophosphamide are reviewed. Potential future treatment options are also discussed. Management algorithms for breakthrough disease are outlined.     

米托蒽醌脂质体制备工艺的研究

目的：优选米托蒽醌脂质体制备工艺。方法：以用形态、粒径、包封率为指标评价工艺。结果：逆相蒸发法制备的的脂质体粒径小,包封率高。结论：逆相蒸发法可用作米托蒽醌脂质体的制备工艺。     

RP-HPLC测定盐酸米托蒽醌葡萄糖注射液中5-羟甲基糠醛的含量

目的 :采用HPLC测定盐酸米托蒽醌葡萄糖注射液中 5 羟甲基糠醛的含量。方法 :用苯基柱 (3 9mm×30 0mm)为分离柱 ,以水 乙腈 庚烷磺酸钠 (75 0∶2 5 0∶2 5 )为流动相 ,检测波长 2 84nm。结果 :平均回收率 99 9% ,RSD=1.83 % (n =5 ) ,在 0 2～ 5 .0 μg·ml 1范围内呈良好线性关系 ,r=0 .9999。结论 :该方法简便、准确可靠     

米托蒽醌联合治疗儿童难治性复发性急性白血病的临床疗效观察

 目的 观察总结米托蒽醌（MTZ）联合治疗儿童难治性复发性急性白血病（RRAL）的疗效。方法 RRAL 12例,急性淋巴细胞白血病（ALL）9例,急性髓性白血病（AML）3例;ALL用VMLP／Dex方案（长春新碱、米托蒽醌、左旋门冬酰胺酶、泼尼松／地塞米松）2～4周;AML用MAE方案（米托蒽醌、阿糖胞苷、依托泊苷）或大剂量阿糖胞苷+依托泊苷。结果 9例ALL,CR 7例,PR 1例,1例未复查;3例AML,CR 2例,NR 1例。总CR率为81.8 %（9／11）,总有效率90.9 %（10／11）。用药后骨髓抑制较明显,大部分病例ANE≤0.1×109／L持续1～2周,轻微肝功能损害,未见药物相关的心脏损害。结论 MTZ不失为治疗儿童难治性复发性急性白血病的有效药物之一,用药后要注意预防和治疗骨髓抑制后出现的各种感染和出血。     

Continuous infusion of low-dose doxorubicin, epirubicin and mitoxantrone in cancer chemotherapy: A review

With the recent development of reliable portable pumps and safe venous access systems, continuous infusion of chemotherapeutic agents on an out-patient basis has become feasible. Advantages of continuous infusion are the long-term exposure of tumour cells to the drug and the fact that most toxic effects are reduced for doxorubicin, epirubicin and mitoxantrone due to elimination of the high peak plasma levels. Preliminary data for doxorubicin suggest that its antitumour activity is maintained. Pharmacokinetic studies with epirubicin and mitoxantrone showed a linear relationship between drug dose infused and the steady-state plasma level for these drugs. The area under the curve for leukocytes drug level was higher during continuous infusion than after an equitoxic bolus injection of epirubicin and mitoxantrone. Well-randomized clinical trials will be necessary to investigate the role of continuous infusion of antracyclines and mitoxantrone in cancer chemotherapy in the future.     

米托蒽醌聚乳酸缓释毫微粒冻干针剂在动物体内的靶向性研究

目的：比较肝靶向米托蒽醌聚乳酸缓释毫微粒（ＤＨＡＱ－ＰＬＡ－ＮＰ）冻干针剂和ＤＨＡＱ水针剂在小鼠体内的分布规律,验证前者的肝靶向性。方法：采用ＨＰＬＣ法测定静注ＤＨＡＱ－ＰＬＡ－ＮＰ和ＤＨＡＱ水针剂后小鼠血液、心、肝、脾、肺、肾的药物浓度,由此计算各器官的相对百分含量。结果：ＤＨＡＱ－ＰＬＡ－ＮＰ冻干针剂在肝脏的分布明显高于ＤＨＡＱ水针剂,在其它器官中的含量则低于水针剂,给药２４小时后药物在肝中的     

肺靶向米托蒽醌明胶微球的研究

采用二步法制备米托蒽醌明胶微球,球径范围为5.1～25.0μm的占总数87.36%,体外释药与原药相比t1/2延长4倍,DTA曲线上的特征吸热峰为133℃,经37℃,RH75%考察3月,几乎无变化。经小鼠体内分布试验表明具有明显的肺靶向性,靶向效率增加3～35倍,肺中药代动力学行为可用一室开放模型描述,平均滞留时间延长10h。     

不同四种方案治疗骨髓增生异常综合征临床研究

目的 研究不同四种方案治疗骨髓增生异常综合征(MDS)疗效,寻求有效的治疗的策略.方法 经FAB标准确诊的MDS患者39例在积极支持治疗下,按个体差异采取不同的化疗方案进行诱导化疗.结果 小剂量阿糖胞苷(LD-Ara-C)组治疗10例,完全缓解(CR)率13.5%;MA组治疗8例,CR率45.0%;DA组治疗6例,CR率40.5%;CAG组治疗15例,CR率60.5%,PR者经2个疗程治疗后,余改用其它方案治疗.结论 CAC方案治疗MDS,CR率高.不良反应小,为MDS患者延长生存期,改善生活质量,提供一种可行的方案.     

强的松龙、长春新碱及米托蒽醌对HL－60细胞株糖皮质激素受体的影响

用“放射受体分析法”研究强的松龙、长春新碱及ＤＨＡＱ对ＨＬ－６０细胞株糖皮质激素受体（ＧＣＲ）的影响，结果发现：①在一定条件下，强的松龙、ＤＨＡＱ能明显地降低ＧＣＲ含量和亲和力，且对ＧＣＲ含量的影响呈明显的时间、药物浓度依赖关系；②相同条件下，长寿新碱亦能一定程度地降低ＧＣＲ含量，但对亲和力影响不明显；③当强的松龙分别与ＤＨＡ０、长春新碱合用时，显示出对ＧＣＲ含量的降低效应有明显的协同作用。     

Subcellular localisation of the antitumour drug mitoxantrone and the induction of DNA damage in resistant and sensitive human colon carcinoma cells

 Cellular uptake and subcellular localisation of the antitumour agent mitoxantrone were studied in a human colon-carcinoma cell line and a mitoxantrone-resistant subline showing features consistent with an atypical multidrug-resistance phenotype involving altered topoisomerase II. Flow cytometry indicated a reduced uptake of mitoxantrone in the resistant line. Confocal microscopy indicated that mitoxantrone-associated fluorescence was primarily found within discrete cytoplasmic inclusions and around the periphery of the nucleus, with low levels being observed within the nucleus. The frequency of cytoplasmic inclusions was reduced in mitoxantrone-resistant cells as compared with parental cells. Fluorescence in cytoplasmic inclusions persisted throughout a 24-h post-treatment period in both cell lines. The results suggest that the persistence of mitoxantrone in cells is a determinant for the continuous induction of DNA damage, perhaps through chronic topoisomerase II trapping, and that modified sequestration may contribute to clinically relevant moderate levels of non-classic multidrug resistance. Received: 9 May 1994 / Accepted: 16 August 1994