甲磺酸伊马替尼治疗慢性髓细胞白血病的不良反应和防治措施

甲磺酸伊马替尼是一种口服的新型酪氨酸激酶抑制剂,已成为慢性髓细胞白血病的一线治疗药物,其不良反应包括血液学不良反应和非血液学不良反应。血液学不良反应主要表现为骨髓抑制(白细胞、血红蛋白和血小板减少);非血液学不良反应主要表现为恶心、呕吐、腹泻、水肿和水钠潴留、肌痛及肌痉挛等。本文就甲磺酸伊马替尼治疗慢性髓细胞白血病所出现的主要不良反应和防治策略进行初步探讨。     

甲磺酸伊马替尼(格列卫)治疗晚期慢性粒细胞性白血病的临床疗效观察

目的:探讨甲磺酸伊马替尼(格列卫)治疗晚期慢性粒细胞白血病的临床疗效及不良反应情况。方法:对我院近年来应用甲磺酸伊马替尼治疗的29例晚期慢性粒细胞白血病患者的临床资料进行回顾性分析,并记录治疗过程中各时间点血常规、骨髓细胞形态学检查、细胞遗传学检查情况,对临床疗效及不良反应进行评价。结果:急变期CML患者血液学缓解率为28.6%,完全细胞遗传学缓解率为0,均明显低于加速期CML患者的73.3%和26.7%,差异均有统计学意义。治疗过程中血液学不良反应主要以白细胞,血小板减少多主,非血液学不良反应可有恶心、呕吐、水肿、骨骼肌酸痛、乏力、头昏、头痛、皮疹等。结论:甲磺酸伊马替尼治疗慢性粒细胞白血病加速期急变期患者疗效好,不良反应少,可耐受且加速期疗效优于急变期。     

甲磺酸伊马替尼治疗慢性粒细胞白血病进展期疗效观察

目的：观察甲磺酸伊马替尼治疗慢性粒细胞白血病（CML）进展期的临床疗效。方法将41例 CML进展期患者随机分为观察组21例和对照组20例。观察组给予甲磺酸伊马替尼,对照组给予常规化疗,比较2组临床疗效和不良反应发生情况。结果观察组总有效率为80.95%高于对照组的20.00%,差异有统计学意义（P ﹤0.05）。结论与传统的常规化疗相比,甲磺酸伊马替尼对 CML 进展期患者近期疗效明显,不良反应可耐受。     

甲磺酸伊马替尼不良反应的文献分析

目的 根据国内临床应用甲磺酸伊马替尼的资料,探讨甲磺酸伊马替尼不良反应的一般规律和特点,为临床合理用药提供参考.方法 检索2003～2009年国内关于甲磺酸伊马替尼致不良反应(ADR)报告29篇,进行回顾性分析.结果 共计1 893例患者使用甲磺酸伊马替尼,其中663例产生不良反应,发生率为35.0%.发生率较高为：水肿203例(30.6%),白细胞减少146例(22.0%),恶心呕吐115例(17.3%),血小板减少107例(16.1%),关节肌肉疼痛72例(10.9%). 结论 临床应重视甲磺酸伊马替尼引起的不良反应,用药时应加强对患者的临床观察,以减少严重不良反应的发生.     

国家药品集中采购对3种抗肿瘤药物临床使用的影响

目的 为国家药品（特别是抗肿瘤药品）集中采购（简称集采）政策的进一步制定提供参考。方法 采用限定日剂量法对国家药品集采政策实施前后上海市某三级综合医院吉非替尼片、甲磺酸伊马替尼片、注射用培美曲塞二钠（均含原研药、仿制药,以及集采中选药）的用药频度（DDDs）、日均费用（DDC）、可负担性等进行分析。结果 政策实施后,3种药品中选品种及仿制药品种的DDC（包括自费和医保）均显著降低,降幅最高的为吉非替尼片,原研药除吉非替尼片外的降幅较小（均不超过15%）;吉非替尼片和甲磺酸伊马替尼片的DDDs显著增加,中选品种占比均超85%。结论 国家药品集采政策的实施,总体上降低了吉非替尼片、甲磺酸伊马替尼片、注射用培美曲塞二钠等3种抗肿瘤药的价格,减少了医保基金压力,减轻了患者的经济负担,但甲磺酸伊马替尼片及注射用培美曲塞二钠的原研药仍属不可负担的药物,有待后续政策出台时解决。     

甲磺酸伊马替尼治疗慢性粒细胞白血病94例临床观察

目的研究甲磺酸伊马替尼治疗慢性粒细胞白血病的临床效果。方法对2004年12月至2010年12月本院入院治疗的188例慢性粒细胞白血病患者进行了研究,随机分为两组,对照组给予联合化疗方法,治疗组给与甲磺酸伊马替尼,比较两组治疗方案的临床效果。结果对照组临床总有效率为22.6%,明显低于治疗组55.3%的临床总有效率,差异有统计学意义（P〈0.05）;两组治疗方案不良反应相当,差异无统计学意义（P〉0.05）。结论甲磺酸伊马替尼治疗慢性粒细胞白血病临床效果显著,无严重不良反应。     

甲磺酸伊马替尼片的不良反应与合理用药

近年来关于甲磺酸伊马替尼片临床疗效报道较多,但鲜见对其不良反应及合理用药的报道。本文对近年来有关甲磺酸伊马替尼不良反应的主要临床表现进行简要叙述,并提出如何合理用药,希望能为临床工作提供一些参考。     

甲磺酸伊马替尼治疗慢性粒细胞白血病66例

目的观察甲磺酸伊马替尼治疗慢性粒细胞白血病的临床疗效。方法选取医院收治的慢性粒细胞白血病患者96例,根据治疗方法不同分为观察组（66例）和对照组（30例）。对照组采用化学治疗方案进行治疗,观察组采用甲磺酸伊马替尼治疗。结果观察组治疗的缓解率（96．67％）高于对照组（80．00％,P〈0．01）;观察组下肢浮肿、恶心呕吐、肝功能异常、皮疹等不良反应发生率均低于对照组（P〈0．05）。结论甲磺酸伊马替尼治疗慢性粒细胞白血病的临床疗效确切,患者耐受性好,值得,陆床借鉴。     

甲磺酸伊马替尼抗肿瘴作用的研究

甲磺酸伊马替尼（imatinib mesylate，商品名Glivec，格列卫）是一种高效特异的酪氨酸激酶抑制剂。1999年美国食品和药品管理局（FDA）批准用于治疗慢性粒细胞白血病（CML），后被FDA、欧盟专利药品评审委员会批准用于胃肠道间质肿瘤（GIST）。2002年该药在我国上市。现将甲磺酸伊马替尼的抗肿瘤作用基础及临床研究情况作一综述。     

甲磺酸伊马替尼治疗慢性髓系白血病慢性期疗效及不良反应分析

目的 探讨甲磺酸伊马替尼(格列卫)治疗慢性髓系白血病慢性期(CML-CP)的疗效,并对其不良反应进行了初步分析.方法 20例CML-CP患者口服伊马替尼300～800mg/d,监测血常规指标、染色体核型及bcr/abl P210转录本表达,用药期间观察其不良反应.结果 中位随访时间15个月(3～36个月),累积获得的完全血液学缓解(CHR)率为90.0%(18/20例),主要细胞遗传学缓解(MCyR)率80.0%(16/20例),分子生物学缓解(CMoR)率为42.9%(6/14例).不良事件:(1)非血液学毒性,如体表水肿(体液潴留)9/20例,肌肉骨骼疼痛7/20例,关节痛6/20例,头痛3/20例;3个月以后均未发现以上不良反应.(2)血液学不良事件:中性粒细胞减少症13/20例(3个月)、7/18例(6个月)、3/10例(12个月),血小板减少症9/20例(3个月)、5/18例(6个月)、3/10例(12个月),贫血2/20例(3个月)、2/18例(6个月)、0/10例(12个月),SGOT/SGPT升高0/20例,胆红素升高0/20例.结论 甲磺酸伊马替尼治疗可以使CML-CP患者获得极高的血液学缓解率和较高的细胞遗传学缓解率,其不良反应多发生于甲磺酸伊马替尼治疗的早期,与其清除恶性克隆有关.随正常造血的恢复,其治疗相关不良反应发生率明显减少.     

Use of arsenic trioxide in haematological malignancies: insight into the clinical development of a novel agent

BACKGROUND: Arsenic trioxide delivers high rates of complete clinical remission in patients with relapsed/refractory acute promyelocytic leukaemia (APL), and is associated with high rates of molecular remission as indicated by PCR negativity for the PML-RARalpha gene. OBJECTIVE: Mitochondria are considered to be the primary intracellular target of arsenic trioxide, and preclinical and mechanistic studies suggest that this agent may have broad applicability in haematological and other malignancies. Investigations of this agent are ongoing in a range of haematological malignancies, and studies in newly diagnosed APL, acute myeloid leukaemia (AML), myelodysplastic syndromes (MDS), multiple myeloma (MM) and chronic myelogenous leukaemia (CML) are reviewed here using published articles and presentations at international congresses to June 2004. Medline was used to source published preclinical and clinical data, and abstract databases and publications from relevant major international haematology/oncology congresses were searched to source updates of preclinical and clinical trial data. FINDINGS: Accumulating data indicate that arsenic trioxide may be a useful addition to the therapeutic regimens that have been so successful in treating newly diagnosed APL, and investigations are ongoing to incorporate this agent into the first-line APL treatment paradigm. Preliminary data from clinical studies indicate that arsenic trioxide has clinical activity as a single agent in MDS and MM, and combination therapies are being investigated. In MM, the combination regimens under study incorporate ascorbic acid, which can enhance the efficacy of arsenic trioxide by reducing intracellular glutathione concentrations. In CML, arsenic trioxide is being investigated in combination with imatinib mesylate in patients who have failed initial imatinib treatment. In AML, although results with single-agent arsenic trioxide were not encouraging, treatment using arsenic trioxide in combination with ascorbic acid is a proposed strategy in elderly patients not able to withstand intensive chemotherapy. CONCLUSION: This versatile agent has a predictable and manageable safety profile and avoids many of the severe toxicities associated with conventional chemotherapies. Ongoing clinical studies will help to define the role of arsenic trioxide in the treatment of haematological malignancies.     

Hsa-miR-203联合伊马替尼对慢性粒细胞白血病K562细胞的作用

目的探讨hsa-miR-203联合甲磺酸伊马替尼（mesylate imatinibMI）对人慢性粒细胞白血病K562细胞的影响。方法体外培养K562细胞,利用Lipofectamine^TM2000将has-miR-203模拟物转染至K562细胞,MT＇F法检测使用miR-203、MI以及两者联合使用对细胞增殖的抑制率,流式细胞术检测对细胞早期凋亡率的影响。结果miR-203转染至K562细胞（24、48、72h）后,联合MI显著抑制K562细胞增殖,抑制效果较各单独使用组作用明显增强。单用miR-203浓度为50μmol·L^-1时的抑制率分别为19．69％、25．62％、35．21％。而联合不同浓度（0．5、1、2、3、4μmol·L^-1）的伊马替尼,抑制率随着作用时间增加,呈时间一依赖效应。单用hsa-miR-203、伊马替尼及两者联合作用于K562细胞48h后,早期凋亡率分别为7．8％、8．9％、12．5％。结论当一定浓度的hsa-miR-203与不同浓度的伊马替尼联合之后,对K562细胞的增殖抑制作用增强,hsa．miR-203提高了K562细胞对伊马替尼的敏感性,其机制可能为共同促进K562细胞早期凋亡有关,并为白血病的治疗提供新的依据。     

Imatinib mesylate in the treatment of chronic myeloid leukaemia

Imatinib mesylate (Gleevec, Glivec), formerly STI571; Novartis Pharmaceuticals) is an inhibitor of the Bcr-abl tyrosine kinase that is central to the pathogenesis of chronic myeloid leukaemia (CML). The remarkable results of imatinib mesylate in clinical trials have rapidly and profoundly changed the management of patients with CML. This article will review the development of this molecularly targeted agent. The clinical trials with imatinib mesylate will be summarised along with the pharmacology of this agent. Despite the impressive responses seen in chronic-phase patients, numerous questions remain. For example, how durable will responses to imatinib mesylate be and is it necessary or possible to improve upon these results? Ongoing efforts to address these issues will be discussed.     

甲磺酸伊马替尼增加顺铂对耐药卵巢癌细胞作用的研究

目的探讨靶向治疗药物甲磺酸伊马替尼(Imatinib mesylate)对耐顺铂人卵巢腺癌细胞株SKOV3/DDP的增殖抑制和诱导凋亡作用以及与顺铂合用的效果。方法 MTT法检测不同浓度甲磺酸伊马替尼、DDP以及联合用药对人卵巢癌耐顺铂细胞株SKOV3/DDP的增殖抑制情况,采用双染色流式细胞术检测甲磺酸伊马替尼对SKOV3/DDP的诱导凋亡作用。结果 MTT法检测出不同药物浓度的甲磺酸伊马替尼作用于SKOV3/DDP细胞呈现细胞生长抑制作用,甲磺酸伊马替尼与不同浓度顺铂联合用药对细胞生长抑制率分别为38.63%、51.55%、66.54%,明显高于DDP单用药组的8.30%、16.68%、30.83%,两组比较差异有统计学意义(P<0.05)。两药合用后的IC50为9.57,是单用顺铂组的4.13倍。甲磺酸伊马替尼与顺铂合用后,早期凋亡率由1.25%增加到12.31%(P<0.05)。结论甲磺酸伊马替尼可以抑制卵巢癌耐DDP细胞株SKOV3/DDP的增殖和诱导细胞凋亡,并显著增强其对DDP的敏感性。     

Current status of unoprostone for the management of glaucoma and the future of its use in the treatment of retinal disease

Imatinib mesylate is a selective and potent small-molecule inhibitor of tyrosine kinases, including Kit, platelet-derived growth factor receptor, and the BCR–Abl fusion protein. Kit plays an important role in gastrointestinal stromal tumours (GISTs) and is one of the most exciting therapeutic targets discovered so far. Clinical trials have consistently shown the dramatic efficacy of imatinib mesylate in patients with GIST. This article will review the development and pharmacology of this small-molecule inhibitor and summarise the clinical trials of imatinib mesylate for the treatment of GIST. Although imatinib mesylate has significantly improved the outcomes of most patients with advanced GIST, unanswered questions remain: what is the role of imatinib mesylate in the pre- and postoperative settings? What is the mechanism of the antitumour activity of imatinib? How do you manage patients whose tumours are refractory to imatinib mesylate?     

Imatinib mesylate in the treatment of gastrointestinal stromal tumour

Imatinib mesylate is a selective and potent small-molecule inhibitor of tyrosine kinases, including Kit, platelet-derived growth factor receptor, and the BCR-Abl fusion protein. Kit plays an important role in gastrointestinal stromal tumours (GISTs) and is one of the most exciting therapeutic targets discovered so far. Clinical trials have consistently shown the dramatic efficacy of imatinib mesylate in patients with GIST. This article will review the development and pharmacology of this small-molecule inhibitor and summarise the clinical trials of imatinib mesylate for the treatment of GIST. Although imatinib mesylate has significantly improved the outcomes of most patients with advanced GIST, unanswered questions remain: what is the role of imatinib mesylate in the pre- and postoperative settings? What is the mechanism of the antitumour activity of imatinib? How do you manage patients whose tumours are refractory to imatinib mesylate?     

Imatinib-associated bilateral gynecomastia and unilateral testicular hydrocele in male patient with metastatic gastrointestinal stromal tumor: a literature review

Imatinib mesylate is a drug that has been approved for treatment of advanced gastrointestinal stromal tumors (GISTs) and patients with leukemia such as chronic myeloid or Philadelphia chromosome-positive acute lymphoblastic. Although it has been described only in one patient with testicular hydrocele and gynecomastia in the literature, several cases of male gynecomastia have been reported with the use of imatinib mesylate in chronic myeloid leukemia (GML). Generally, male mastoplasia resolves after discontinuation of imatinib treatment. We report a 73-year-old male with metastatic GISTs who developed gynecomastia and unilateral testicular hydrocele while receiving imatinib mesylate. Nine months after commencing imatinib treatment, gynecomastia and testicular hydrocele were determined. Hormone analyses requested showed serum testosterone levels below and serum estrogen levels above normal limits. During the first month after discontinuing imatinib mesylate treatment, serum testosterone level was normal and there was a partial regression in gynecomastia and testicular hydrocele. To our knowledge, this is the second report of male gynecomastia following imatinib mesylate treatment of a patient with GIST. In conclusion, male patients who are to receive treatment with imatinib mesylate may be monitored for serum testosterone levels and for other reproductive hormone profiles before initiation of the treatment and their breasts may be examined during follow-up visits.     

Imatinib-induced pancreatitis

Drug-induced pancreatitis is a rare but serious complication of many drugs, some of which have been well documented. Here we present a case of a middle-aged man with chronic myeloid leukemia who developed acute pancreatitis after being initiated on imatinib mesylate. The case history, the pharmacodynamics, uses, and adverse effects of imatinib mesylate are discussed in detail.     

不同性激素对P-糖蛋白表达水平及甲磺酸伊马替尼转运的影响

目的：探讨在ABCB1（1199G/A）重组细胞模型中不同性激素对P-糖蛋白（P-gp）表达水平及甲磺酸伊马替尼转运的影响。方法：将构建的ABCB1_1199G/wt和ABCB1_1199A/mut重组质粒稳定转染入HEK293细胞中,采用RT-PCR和Western Blot分别检测不同性激素对P-gp mRNA和蛋白的表达水平;采用HPLC检测性激素对甲磺酸伊马替尼累积量的影响。结果：浓度梯度的性激素（雌酮、雌三醇雌二酮、黄体酮和睾酮）刺激ABCB1_1199G/wt 和ABCB1_1199A/mut重组细胞后,雌酮和雌三醇能刺激P-gp mRNA和蛋白表达水平,且雌三醇上调ABCB1_1199A/mut mRNA的表达水平显著高于ABCB1_1199G/wt;雌酮和雌三醇可降低甲磺酸伊马替尼在细胞内的累积量,产生对伊马替尼的耐药性。结论：雌酮和雌三醇增加了细胞内P-gp的表达,并促进P-gp介导甲磺酸伊马替尼的转运能力。