Clinical Medicine and Therapeutics最新文献

{"title":"Safety and Efficacy of Panitumumab in the Treatment of Metastatic Colorectal Cancer","authors":"Daniel J. Freeman","doi":"10.4137/CMT.S2039","DOIUrl":"https://doi.org/10.4137/CMT.S2039","url":null,"abstract":"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.","PeriodicalId":10428,"journal":{"name":"Clinical Medicine and Therapeutics","volume":"91 1","pages":"633-645"},"PeriodicalIF":0.0,"publicationDate":"2009-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86872860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Secondary Stroke Prevention, and the Role of Antiplatelet Therapies","authors":"H. Kirshner","doi":"10.4137/CMT.S2208","DOIUrl":"https://doi.org/10.4137/CMT.S2208","url":null,"abstract":"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.","PeriodicalId":10428,"journal":{"name":"Clinical Medicine and Therapeutics","volume":"136 1","pages":"601-612"},"PeriodicalIF":0.0,"publicationDate":"2009-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76393207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First-line Treatment of Metastatic Breast Cancer: Focus on Bevacizumab:","authors":"T. Fujii, Hiroki Takahashi, R. Matsubayashi, Y. Inoue, M. Takenaka, U. Toh, M. Kage, H. Yamana, K. Shirouzu","doi":"10.4137/CMT.S1981","DOIUrl":"https://doi.org/10.4137/CMT.S1981","url":null,"abstract":"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.","PeriodicalId":10428,"journal":{"name":"Clinical Medicine and Therapeutics","volume":"290 1","pages":"583-593"},"PeriodicalIF":0.0,"publicationDate":"2009-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73537450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hormone Refractory Prostate Cancer: Focus on Sipuleucel-T","authors":"C. Doehn, M. Sommerauer, Xiyuan Guo, I. Kausch, D. Jocham","doi":"10.4137/CMT.S1084","DOIUrl":"https://doi.org/10.4137/CMT.S1084","url":null,"abstract":"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.","PeriodicalId":10428,"journal":{"name":"Clinical Medicine and Therapeutics","volume":"1 1","pages":"595-600"},"PeriodicalIF":0.0,"publicationDate":"2009-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74011794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Review of Trastuzumab-Based Therapy in Patients with HER2-positive Metastatic Breast Cancer","authors":"D. Church, C. Price","doi":"10.4137/CMT.S35","DOIUrl":"https://doi.org/10.4137/CMT.S35","url":null,"abstract":"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.","PeriodicalId":10428,"journal":{"name":"Clinical Medicine and Therapeutics","volume":"38 1","pages":"557-570"},"PeriodicalIF":0.0,"publicationDate":"2009-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89973358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacotherapy of Excessive Sleepiness: Focus on Armodafinil","authors":"M. Russo","doi":"10.4137/CMT.S1994","DOIUrl":"https://doi.org/10.4137/CMT.S1994","url":null,"abstract":"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.","PeriodicalId":10428,"journal":{"name":"Clinical Medicine and Therapeutics","volume":"65 1","pages":"415-432"},"PeriodicalIF":0.0,"publicationDate":"2009-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79240949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and Efficacy of Ambrisentan in the Treatment of Pulmonary Arterial Hypertension","authors":"C. Valerio, P. Kabunga, J. Coghlan","doi":"10.4137/CMT.S2675","DOIUrl":"https://doi.org/10.4137/CMT.S2675","url":null,"abstract":"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...","PeriodicalId":10428,"journal":{"name":"Clinical Medicine and Therapeutics","volume":"40 1","pages":"541-556"},"PeriodicalIF":0.0,"publicationDate":"2009-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76112210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Options in Multiple Myeloma: Focus on Bortezomib","authors":"G. Roodman","doi":"10.4137/CMT.S2119","DOIUrl":"https://doi.org/10.4137/CMT.S2119","url":null,"abstract":"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.","PeriodicalId":10428,"journal":{"name":"Clinical Medicine and Therapeutics","volume":"20 1","pages":"495-503"},"PeriodicalIF":0.0,"publicationDate":"2009-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74674833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Review of Nelarabine in the Treatment of T-cell Lymphoblastic Leukemia/Lymphoma","authors":"F. Hernandez-Ilizaliturri, M. Czuczman","doi":"10.4137/CMT.S1954","DOIUrl":"https://doi.org/10.4137/CMT.S1954","url":null,"abstract":"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...","PeriodicalId":10428,"journal":{"name":"Clinical Medicine and Therapeutics","volume":"40 1","pages":"505-511"},"PeriodicalIF":0.0,"publicationDate":"2009-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83541301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Review of Levofloxacin for the Treatment of Bacterial Infections","authors":"G. Noel","doi":"10.4137/CMT.S28","DOIUrl":"https://doi.org/10.4137/CMT.S28","url":null,"abstract":"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...","PeriodicalId":10428,"journal":{"name":"Clinical Medicine and Therapeutics","volume":"4 1","pages":"433-458"},"PeriodicalIF":0.0,"publicationDate":"2009-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82661900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}