LEARNING OBJECTIVESAfter completing this course, the reader will be able to:1. Describe the molecular mechanisms of action, safety profile, rationale for NSCLC treatment, and main current evidence in NSCLC treatment using the multikinase inhibitors sorafenib and sunitinib.2. Summarize the main clinical trials performed with sorafenib and sunitinib in the treatment of solid tumors.3. Describe the clinical trials performed with sorafenib and sunitinib in NSCLC and suggest the future clinical development of these two drugs in the treatment of NSCLC.Access and take the CME test online and receive 1 AMA PRA Category 1 Credit ™ at CME.TheOncologist.com CME CME ABSTRACT
Small cell lung cancer (SCLC) accounts for approximately 20% of lung carcinomas. Chemotherapy is the cornerstone of treatment for SCLC. In limited disease, the median survival time is about 12-16 months, with a 4%-5% long-term survival rate; in extensive disease the median survival time is 7-11 months. More than 50% of lung cancer patients are diagnosed when they are over the age of 65, and about 30% are over 70. Elderly patients tolerate chemotherapy poorly compared with their younger counterparts, because of agerelated progressive reductions in organ function and comorbidities. The standard therapy for limited disease is combined chemoradiotherapy, followed by prophylactic brain irradiation for patients achieving complete responses. In the elderly, the addition of radiotherapy to chemotherapy must be carefully evaluated, considering the slight survival benefit and potential for substantial toxicity incurred with this treatment. The best approach is to design clinical trials that specifically include geriatric assessment to develop active and well-tolerated chemotherapy regimens for elderly SCLC patients. Survival improvement for SCLC patients requires a better understanding of tumor biology and the subsequent development of novel therapeutic strategies. Several targeted agents have been introduced into clinical trials in SCLC, but a minority of these new agents offers a promise of improved outcomes, and negative results are reported more commonly than positive ones. This review focuses on the main issues in the treatment of elderly SCLC patients. The Oncologist 2005;10:399-411The Oncologist 2005;10:399-411 www.TheOncologist.com
Non small cell lung cancer (NSCLC) is a lethal disease with poor prognosis. The main percentage of NSCLC patients are diagnosed to have an advanced disease. Standard treatment, such as chemotherapy and radiotherapy, has apparently reached a plateau of effectiveness in improving survival of advanced NSCLC patients. Hence, considerable efforts have started to be made in order to identify novel targets for new biological agents which may safely and effectively be administered to advanced NSCLC patients. Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) and its receptors play an essential role in tumour proliferation. Approaches targeting EGFR and VEGF include monoclonal antibodies (mAbs) and small molecules inhibiting the corresponding receptor-tyrosine kinase activity. Erlotinib is a small molecule inhibitor of EGFR tyrosine-kinase which has brought significant improvements in median survival, quality of life and related symptoms, in an unselected population of advanced NSCLC patients in the second- or third-line setting. Bevacizumab, an anti-VEGF recombinant humanized mAb, is the first targeted agent which, when combined with chemotherapy, reported superior efficacy versus chemotherapy alone in the treatment of advanced NSCLC. ZD6474, a small molecule targeting VEGF tyrosine-kinase activity, showing early evidence of antitumour activity and the excellent toxicity profile, seems to be a promising agent for the treatment of advanced NSCLC. This review shows the latest and the future developments of erlotinib, bevacizumab and ZD6474 in the treatment of advanced NSCLC patients.
Erlotinib may be effective in patients with non-small cell lung cancer who were previously and successfully treated with gefitinib. However, careful selection of these patients is needed.
nation of plasma alpha-glutathione S-transferases in patients with HCVrelated chronic infection: its significance and possible clinical relevance.Abstract: Aims/Background: Alpha-glutathione S-transferases (a-GST) are the cytoplasmatic class of enzymes responsible for cellular detoxifying processes. We evaluated the plasma a-GST activity in relation to chronic infection caused by hepatitis C virus (HCV). Methods: Eighteen anti-HCV-negative healthy subjects (controls), 32 anti-HCV-positive subjects with a constant normality of alanine aminotransferases (ALT) and gamma-glutamyl transpeptidase (y-GT) levels ("apparently healthy carriers"), and 85 patients with HCV-related chronic liver disease (40 chronic hepatitis, 27 cirrhosis, and 18 with hepatocellular carcinoma) were studied. We assayed plasma a-GST in all subjects upon their entry into the study; and every 6 months for 3 years in the control group and in anti-HCV apparently healthy carriers. Results: Alpha-GST values were significantly higher than normal values in 57% of the 21 HCV-RNA-positive apparently healthy carriers and in none of 11 persistently HCV-RNAnegative subjects; the highest increment of a-GST was documented in patients with chronic hepatitis. We did not observe correlation among HCV-RNA, histological activity, y-GT and ALT or a-GST values. Conclusions: Therefore, the increment of plasma a-GST indicates a liver involvement even when ALT levels are normal. This may be clinically relevant to "apparently healthy carriers" whose plasma a-GST values. when 1 increased, might need further evaluation.Alpha-glutathione S-transferases (a-GST) are the "basic" class of a large enzyme family; they are ubiquitously distributed in the cells, particularly in the hepatocytes. Their biological functions are to transport hepatic anions, to conjugate glutathione (GSH) with various electrophiles and hydroperoxides, to synthesize prostaglandins and leukotrienes, and to activate selenium-independent glutathioneperoxidase (1-4).Alpha-GST are distributed throughout the liver lobule, represent about 5% of the cytosol in the hepatocytes and quickly rise in the plasma after liver damage. Their half-life iseabout 60 min, and when increased, plasma levels return to normal in about 5 days. Conversely, alanine aminotransferCarmela Loguerciol ,
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.