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Safety and Efficacy of Panitumumab in the Treatment of Metastatic Colorectal Cancer 帕尼珠单抗治疗转移性结直肠癌的安全性和有效性
Pub Date : 2009-06-12 DOI: 10.4137/CMT.S2039
Daniel J. Freeman
Therapies targeting epidermal growth factor receptor (EGFR) are a promising recent development in the treatment of metastatic colorectal cancer (mCRC). Panitumumab is a fully human anti-EGFR monoclonal antibody that competitively inhibits the binding of all known EGFR ligands, including epidermal growth factor and transforming growth factor alpha, to cells expressing EGFR. In patients with mCRC, panitumumab monotherapy has resulted in favorable clinical responses, including increases in objective response rate, stable disease rate, and progression-free survival. Panitumumab has also shown promising antitumor activity in combination with selected chemotherapy regimens. Responses and improvements in progression-free survival associated with panitumumab monotherapy in patients with mCRC appear to be confined to patients whose tumors express wild-type KRAS. Therapy with panitumumab is generally well tolerated; the most common adverse events observed include skin-related toxicities, gastrointestinal toxicities, and hypomagnesemia. Infusion reactions are rare, and the agent has low immunogenicity.
以表皮生长因子受体(EGFR)为靶点的治疗在转移性结直肠癌(mCRC)的治疗中是一个有前景的新进展。Panitumumab是一种全人抗EGFR单克隆抗体,竞争性地抑制所有已知EGFR配体(包括表皮生长因子和转化生长因子α)与表达EGFR的细胞的结合。在mCRC患者中,帕尼单抗单药治疗产生了良好的临床反应,包括客观反应率增加、发病率稳定和无进展生存期。Panitumumab与选定的化疗方案联合也显示出有希望的抗肿瘤活性。panitumumab单药治疗与mCRC患者的无进展生存期相关的反应和改善似乎仅限于肿瘤表达野生型KRAS的患者。帕尼单抗治疗通常耐受性良好;观察到的最常见的不良事件包括皮肤相关毒性、胃肠道毒性和低镁血症。输注反应罕见,且免疫原性低。
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引用次数: 3
Secondary Stroke Prevention, and the Role of Antiplatelet Therapies 二级卒中预防和抗血小板治疗的作用
Pub Date : 2009-06-11 DOI: 10.4137/CMT.S2208
H. Kirshner
This review considers treatments of proved efficacy in secondary stroke prevention, with an emphasis on antiplatelet therapy. Most strokes could be prevented, if readily available lifestyle and risk factor modifications could be applied to everyone. In secondary stroke prevention, the same lifestyle and risk factor modifications are also important, along with anticoagulation for patients with cardiac sources of embolus, carotid procedures for patients with significant internal carotid artery stenosis, and antiplatelet therapy. For patients with noncardioembolic ischemic strokes, FDA-approved antiplatelet agents are recommended and preferred over anticoagulants. ASA, clopidogrel, and ASA + ER-DP are recognized as accepted first-line options for secondary prevention of noncardioembolic ischemic stroke. Combined antiplatelet therapy with ASA + clopidogrel has not been shown to carry benefit greater than risk in stroke or TIA patients. Aspirin and extended release dipyridamole appeared to carry a greater benefit over aspirin alone in individual studies, leading to a recommendation of this agent in the AHA guidelines, but the recently completed PRoFESS trial showed no difference in efficacy between clopidogrel and aspirin with extended release dipyridamole, and clopidogrel had better tolerability and reduced bleeding risk.
这篇综述考虑了在继发性卒中预防中已证实有效的治疗方法,重点是抗血小板治疗。如果每个人都能改变生活方式和危险因素,那么大多数中风都是可以预防的。在二级卒中预防中,同样的生活方式和危险因素的改变也很重要,同时对心脏源性栓塞患者进行抗凝治疗,对颈内动脉明显狭窄患者进行颈动脉手术,以及抗血小板治疗。对于非心源性缺血性中风患者,推荐使用fda批准的抗血小板药物,且优于抗凝药物。ASA、氯吡格雷和ASA + ER-DP是公认的非心栓塞性缺血性卒中二级预防的一线选择。在卒中或TIA患者中,ASA +氯吡格雷联合抗血小板治疗并未显示出获益大于风险。在个别研究中,阿司匹林和缓释双嘧达莫似乎比阿司匹林单独使用有更大的益处,导致AHA指南推荐使用该药物,但最近完成的PRoFESS试验显示氯吡格雷和阿司匹林与缓释双嘧达莫的疗效没有差异,氯吡格雷具有更好的耐受性和降低出血风险。
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引用次数: 0
First-line Treatment of Metastatic Breast Cancer: Focus on Bevacizumab: 转移性乳腺癌的一线治疗:以贝伐单抗为重点
Pub Date : 2009-06-10 DOI: 10.4137/CMT.S1981
T. Fujii, Hiroki Takahashi, R. Matsubayashi, Y. Inoue, M. Takenaka, U. Toh, M. Kage, H. Yamana, K. Shirouzu
As vascular endothelial growth factor (VEGF) plays a central role in tumor growth, invasion and metastasis, inhibiting tumor angiogenesis by blocking the actions of VEGF is a rational therapeutic strategy. Drugs targeting the VEGF system are currently in development and at the most advanced stage of development is bevacizumab. The effect of bevacizumab on breast cancer has been examined in many clinical trials, and promising results have been reported. The clinical effect of bevacizumab monotherapy for breast cancer is not clear; however, the ECOG-E2100 study showed that first-line anti-angiogenic therapy using bevacizumab combined with paclitaxel clearly improved the response for earlier stage metastatic breast cancer (MBC). As a stronger anti-tumor effect is expected when prescribing bevacizumab for patients at an early stage of MBC, many first-line clinical trials using bevacizumab with other combination regimens are currently ongoing. Although the common side effects of bevacizumab are hypertension, proteinuria, wound-healing complications, and thromboembolism, it is a comparatively safe agent. It is expected that the many ongoing clinical trials will establish bevacizumab as a standard first-line therapy for MBC.
由于血管内皮生长因子(vascular endothelial growth factor, VEGF)在肿瘤的生长、侵袭和转移过程中起着核心作用,因此通过阻断VEGF的作用来抑制肿瘤血管生成是一种合理的治疗策略。靶向VEGF系统的药物目前正在开发中,目前处于开发的最高阶段是贝伐单抗。贝伐单抗对乳腺癌的影响已经在许多临床试验中进行了检验,并报道了令人鼓舞的结果。贝伐单抗单药治疗乳腺癌的临床效果尚不清楚;然而,ECOG-E2100研究显示,贝伐单抗联合紫杉醇的一线抗血管生成治疗明显改善了早期转移性乳腺癌(MBC)的疗效。由于贝伐珠单抗对早期MBC患者的抗肿瘤作用更强,目前正在进行许多使用贝伐珠单抗与其他联合方案的一线临床试验。虽然贝伐单抗常见的副作用是高血压、蛋白尿、伤口愈合并发症和血栓栓塞,但它是一种相对安全的药物。预计许多正在进行的临床试验将使贝伐单抗成为MBC的标准一线治疗方法。
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引用次数: 0
Hormone Refractory Prostate Cancer: Focus on Sipuleucel-T 激素难治性前列腺癌:聚焦于Sipuleucel-T
Pub Date : 2009-06-08 DOI: 10.4137/CMT.S1084
C. Doehn, M. Sommerauer, Xiyuan Guo, I. Kausch, D. Jocham
Sipuleucel-T is a vaccine based on autologous antigen presenting cells that are loaded with an antigen-cytokine (prostatic acid phosphatase and granulocyte-macrophage colony-stimulating factor) fusion product. Sipuleucel-T is given intravenous in weeks 0, 2, and 4. Within phase I–III trials, patients with metastatic hormone-refractory prostate cancer have been treated. In these trials an activation of the immune system could be demonstrated. Also, some clinical responses could be documented. Moreover, in a placebo-controlled phase III trial including 127 patients a statistical significantly prolongation of survival was achieved. Side effects from the vaccine are rather mild and included fever, myalgia, fatigue and others. The Food and Drug Administration in the United States requested further data before possible approval of sipuleucel-T.
Sipuleucel-T是一种基于自体抗原呈递细胞的疫苗,该细胞装载抗原-细胞因子(前列腺酸性磷酸酶和粒细胞-巨噬细胞集落刺激因子)融合产物。Sipuleucel-T在第0、2和4周静脉注射。在I-III期试验中,转移性激素难治性前列腺癌患者已经接受了治疗。在这些试验中,免疫系统的激活可以被证明。此外,一些临床反应可以被记录下来。此外,在一项包括127名患者的安慰剂对照III期试验中,生存率显著延长。疫苗的副作用相当轻微,包括发烧、肌痛、疲劳等。美国食品和药物管理局要求在可能批准sipuleucel-T之前提供进一步的数据。
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引用次数: 0
A Review of Trastuzumab-Based Therapy in Patients with HER2-positive Metastatic Breast Cancer 基于曲妥珠单抗治疗her2阳性转移性乳腺癌的研究综述
Pub Date : 2009-06-08 DOI: 10.4137/CMT.S35
D. Church, C. Price
The ERBB2 or HER2 receptor is overexpressed in 25% of breast cancers and is associated with poor prognosis. Trastuzumab, a monoclonal antibody targeting HER2 has been demonstrated to improve survival when combined with chemotherapy for the treatment of HER2 overexpressing metastatic breast cancer (MBC). Further studies have endeavoured to clarify the optimum chemotherapy regimen in combination with trastuzumab for MBC and its use together with novel biological agents. This review summarises these data together with preclinical studies exploring the mechanism of trastuzumab action and causes of drug resistance. The frequent incidence of brain metastases in patients on trastuzumab is highlighted, and data on the continuation of trastuzumab following CNS and non-CNS progression reviewed.
ERBB2或HER2受体在25%的乳腺癌中过表达,并与预后不良相关。曲妥珠单抗是一种靶向HER2的单克隆抗体,已被证明在联合化疗治疗HER2过表达转移性乳腺癌(MBC)时可提高生存率。进一步的研究努力阐明曲妥珠单抗联合治疗MBC的最佳化疗方案及其与新型生物制剂的联合使用。这篇综述总结了这些数据以及探索曲妥珠单抗作用机制和耐药原因的临床前研究。强调曲妥珠单抗患者脑转移的频繁发生率,并回顾了曲妥珠单抗在中枢神经系统和非中枢神经系统进展后继续使用的数据。
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引用次数: 1
Pharmacotherapy of Excessive Sleepiness: Focus on Armodafinil 过度嗜睡的药物治疗:以阿米达非尼为重点
Pub Date : 2009-05-28 DOI: 10.4137/CMT.S1994
M. Russo
Excessive sleepiness (ES) is responsible for significant morbidity and mortality due to its association with cardiovascular disease, cognitive impairment, and occupational and transport accidents. ES is also detrimental to patients’ quality of life, as it affects work and academic performance, social interactions, and personal relationships. Armodafinil is the R-enantiomer of the established wakefulness-promoting agent modafinil, which is a racemic mixture of both the R- and S-enantiomers. R-modafinil has a longer half-life and is present at higher circulating concentrations than the S-enantiomer following chronic administration of modafinil and may therefore be the enantiomer predominantly responsible for the beneficial effects of the racemic compound. Armodafinil has been approved by the Food and Drug Administration for the improvement of ES associated with narcolepsy, shift-work disorder, and obstructive sleep apnea following a program of randomized, placebo-controlled clinical trials. This comprehensive medication review discusses the pharmacologic profile of armodafinil and the current evidence regarding its efficacy, safety, and tolerability; appraises patient-reported outcomes data; and suggests additional indications in which armodafinil may be of use.
过度嗜睡(ES)与心血管疾病、认知障碍以及职业和交通事故有关,是导致严重发病率和死亡率的原因。ES也对患者的生活质量有害,因为它会影响工作和学习成绩、社会交往和个人关系。莫达非尼是已建立的清醒促进剂莫达非尼的R-对映体,后者是R-和s-对映体的外消旋混合物。r -莫达非尼的半衰期较长,在长期服用莫达非尼后,其循环浓度高于s -对映体,因此r -莫达非尼可能是外消旋化合物产生有益作用的主要对映体。经过一项随机、安慰剂对照的临床试验,Armodafinil已被美国食品和药物管理局(fda)批准用于改善与发作性睡病、轮班工作障碍和阻塞性睡眠呼吸暂停相关的ES。这篇全面的药物综述讨论了阿莫达非尼的药理学特征以及目前关于其有效性、安全性和耐受性的证据;评估患者报告的结果数据;并提出了可能使用阿莫达非尼的其他适应症。
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引用次数: 7
Safety and Efficacy of Ambrisentan in the Treatment of Pulmonary Arterial Hypertension 安布里森坦治疗肺动脉高压的安全性和有效性
Pub Date : 2009-05-27 DOI: 10.4137/CMT.S2675
C. Valerio, P. Kabunga, J. Coghlan
Three different classes of specific therapy exist for pulmonary arterial hypertension. Ambrisentan belongs to the endothelin receptor antagonist (ERA) class of drugs, which inhibit the action of Endothelin-1; a potent vasoconstrictor and mitogen. Unlike bosentan and sitaxentan, it has a propanoic-acid based structure and like sitaxentan it has selective affinity for type A Endothelin receptors. Two large randomized controlled trials (ARIES-1 and ARIES-2) have demonstrated clinical benefit with ambrisentan in pulmonary arterial hypertension by repeated measurement of 6-minute walk distance. The most common adverse effect associated with ambrisentan use is peripheral edema, the incidence of liver enzyme elevation seen is lower than for other ERAs. Ambrisentan is safe in combination with warfarin and sildenafil. It offers further flexibility in the treatment of PAH as monotherapy and in combination. Although encouraging, trial data do not exhibit improved efficacy compared with other ERAs or sildenafil and t...
肺动脉高压有三种不同的治疗方法。氨布里森坦属于内皮素受体拮抗剂(ERA)类药物,可抑制内皮素-1的作用;一种有效的血管收缩剂和有丝分裂原。与波生坦和西他坦不同,它具有丙酸基结构,与西他坦一样,它对a型内皮素受体具有选择性亲和力。两项大型随机对照试验(ARIES-1和ARIES-2)通过重复测量6分钟步行距离证明了ambrisentan对肺动脉高压的临床益处。与使用氨布森坦相关的最常见不良反应是外周水肿,肝酶升高的发生率低于其他era。安布里森坦与华法林和西地那非合用是安全的。它为治疗多环芳烃提供了进一步的灵活性,作为单一疗法和联合疗法。虽然令人鼓舞,但与其他era或西地那非相比,试验数据并未显示出更高的疗效。
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引用次数: 2
Therapeutic Options in Multiple Myeloma: Focus on Bortezomib 多发性骨髓瘤的治疗选择:重点是硼替佐米
Pub Date : 2009-05-26 DOI: 10.4137/CMT.S2119
G. Roodman
Myeloma is the most frequent malignancy to involve the bone. The bone microenvironment plays an important role in supporting tumor growth, bone destruction and resistance to chemotherapy. Until the advent of novel therapies such as bortezomib, the prognosis for patients with myeloma did not change significantly over 40 years. The median survival of patients until 1996 was approximately 30 months, and has now improved to almost 5 years. Bortezomib is the first-in-class proteasome antagonist approved for treatment of myeloma. It is active in newly diagnosed, relapsed and refractory patients and is now being used as a platform for combinations with other new agents for myeloma. Its major side effects include neuropathy and thrombocytopenia. In addition to its anti-myeloma effect, bortezomib also targets the bone microenvironment and can inhibit osteoclast formation, and stimulate osteoblast activity in patients with myeloma. Potentially, combination of bortezomib with other agents that stimulate bone formation or block bone resorption will further enhance the anti-myeloma effects of bortezomib and overcome the contribution of the tumor microenvironment to myeloma growth. Multiple myeloma (MM) is a primary plasma cell malignancy, which is the most frequent malignancy to involve the bone. Over 80% of patients with MM have bone involvement during the course of their disease. 1 The prognosis for patients with MM had not changed significantly over the last 40 years until the last 5 years. 2 The median survival of patients up to 1996 was approximately 30 months, and this has now improved to almost 5 years with the advent of newer therapies. The new therapies that have made a major impact on the survival and quality of life in MM patients have been the introduction of immunomodulatory drugs (IMiDs) and bortezomib, which is the first-in-class proteasome antagonist to come to the clinic. Both the IMiDs, thalidomide and lenalidomide, and bortezomib have been used alone and in combination with dexamethasone as well as with each other to treat MM patients. These agents have increased response rates and prolonged both progression free survival and overall survival of patients with relapsed and/or refractory MM from 12 months to 24 months and newly diagnosed MM from 30 months to 45 months. Further, these drugs also have effects on MM bone disease, either by suppressing osteoclast (OCL) activity or in the case of bortezomib enhancing osteoblast (OBL) activity. In this review, we will examine the mechanism of action of bortezomib and its capacity to target MM cells as well as the marrow microenvironment in patients with MM.
骨髓瘤是最常见的累及骨骼的恶性肿瘤。骨微环境在支持肿瘤生长、骨破坏和化疗抵抗中起着重要作用。在新型治疗方法如硼替佐米出现之前,骨髓瘤患者的预后在40年内没有显著变化。到1996年,患者的中位生存期约为30个月,现在已改善到近5年。硼替佐米是被批准用于治疗骨髓瘤的一流蛋白酶体拮抗剂。它在新诊断,复发和难治性患者中具有活性,现在被用作与其他新药物联合治疗骨髓瘤的平台。其主要副作用包括神经病变和血小板减少症。硼替佐米除具有抗骨髓瘤作用外,还能靶向骨微环境,抑制破骨细胞的形成,刺激骨髓瘤患者的成骨细胞活性。硼替佐米与其他刺激骨形成或阻止骨吸收的药物联合使用,可能会进一步增强硼替佐米的抗骨髓瘤作用,克服肿瘤微环境对骨髓瘤生长的影响。多发性骨髓瘤是一种原发浆细胞恶性肿瘤,是最常见的累及骨的恶性肿瘤。超过80%的MM患者在病程中有骨受累。1 MM患者的预后在过去40年中直到最近5年才发生显著变化。截至1996年,患者的中位生存期约为30个月,随着新疗法的出现,现在已改善至近5年。对MM患者的生存和生活质量产生重大影响的新疗法是免疫调节药物(IMiDs)和硼替佐米的引入,硼替佐米是第一个进入临床的同类蛋白酶体拮抗剂。IMiDs、沙利度胺和来那度胺以及硼替佐米都曾单独使用,也曾与地塞米松联合使用,也曾相互联合使用,用于治疗MM患者。这些药物提高了缓解率,将复发和/或难治性MM患者的无进展生存期和总生存期从12个月延长至24个月,将新诊断的MM从30个月延长至45个月。此外,这些药物也通过抑制破骨细胞(OCL)活性或硼替佐米增强成骨细胞(OBL)活性对MM骨病有影响。在这篇综述中,我们将研究硼替佐米的作用机制及其靶向MM细胞和MM患者骨髓微环境的能力。
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引用次数: 3
A Review of Nelarabine in the Treatment of T-cell Lymphoblastic Leukemia/Lymphoma 奈拉滨治疗t淋巴母细胞白血病/淋巴瘤的研究进展
Pub Date : 2009-05-21 DOI: 10.4137/CMT.S1954
F. Hernandez-Ilizaliturri, M. Czuczman
Patients with relapsed/refractory T-cell acute lymphocytic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) have a dismal prognosis. Prior to the development of novel purine analogs, salv...
复发/难治性t细胞急性淋巴细胞白血病(T-ALL)和t细胞淋巴母细胞淋巴瘤(T-LBL)患者预后不佳。在开发新的嘌呤类似物之前,salv…
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引用次数: 6
A Review of Levofloxacin for the Treatment of Bacterial Infections 左氧氟沙星治疗细菌感染的研究进展
Pub Date : 2009-05-15 DOI: 10.4137/CMT.S28
G. Noel
Completing its initial phases of drug development in the mid 1990s as the one of the first fluoroquinolones that could be used with confidence to treat respiratory tract infections, levofloxacin went on to become one of the most widely prescribed antibiotics in the world. Available in both oral (po) and intravenous (IV) formulations and with characteristics of over 90% bioavailability, distribution into both extracellular and intracellular pulmonary compartments, highly predictable pharmacokinetics with over 90% of the drug being excreted unchanged in urine, and reliable activity against a broad spectrum of clinically important pathogens, levofloxacin has been used successfully to treat patients with a variety of serious infectious diseases as well as common infections most often treated outside of the hospital setting. Results of clinical trials involving patients with respiratory tract, urinary tract, and skin infections have consistently shown rates of clinical success and bacteriological eradication t...
左氧氟沙星作为首批可以放心用于治疗呼吸道感染的氟喹诺酮类药物之一,在20世纪90年代中期完成了药物开发的初始阶段,随后成为世界上处方最广泛的抗生素之一。有口服(po)和静脉注射(IV)两种剂型,具有90%以上的生物利用度,分布在细胞外和细胞内肺室,高度可预测的药代动力学,90%以上的药物在尿液中排泄不变,对广泛的临床重要病原体具有可靠的活性。左氧氟沙星已成功用于治疗各种严重传染病患者以及最常在医院外治疗的常见感染。涉及呼吸道、泌尿道和皮肤感染患者的临床试验结果一致显示临床成功率和细菌根除率。
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引用次数: 34
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Clinical Medicine and Therapeutics
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