Expert opinion on investigational drugs
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Expert Opin Investig Drugs · Sep 2009
ReviewAnidulafungin and voriconazole in invasive fungal disease: pharmacological data and their use in combination.
The incidence of invasive fungal infections has been increasing since the 1980s due to a growing population of immunocompromised and critically ill patients with associated risk factors including immunosuppressive chemotherapy, prolonged periods on intensive care units and infection with HIV. Persons who are severely immunocompromised are particularly vulnerable to infection from molds and yeasts that are often found naturally in the environment. ⋯ Newly available drugs as those in the echinocandin class include caspofungin, micafungin and anidulafungin, as well as the newer generation triazoles, voriconazole and posaconazole. In this review, the in vitro and in vivo activity of anidulafungin and voriconazole, both new antimycotic substances with a different mode of action, are analyzed.
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Expert Opin Investig Drugs · Aug 2009
ReviewGlioblastoma multiforme: a review of where we have been and where we are going.
Malignant gliomas such as glioblastoma multiforme (GBM) present some of the greatest challenges in the management of cancer patients worldwide, despite notable recent achievements in oncology. Even with aggressive surgical resections using state-of-the-art preoperative and intraoperative neuroimaging, along with recent advances in radiotherapy and chemotherapy, the prognosis for GBM patients remains dismal: median survival after diagnosis is about 14 months. Established good prognostic factors are limited, but include young age, high Karnofsky Performance Status (KPS), high mini-mental status examination score, O6-methylguanine methyltransferase promoter methylation, and resection of > 98% of the tumor. ⋯ GBM research is being conducted worldwide at a remarkable pace, with some of the more recent promising studies focused on identification of aberrant genetic events and signaling pathways, tumor stem cell identification and characterization, modulation of tumor immunological responses, combination therapies, and understanding of the rare long-term survivors. Past treatment strategies have failed for various reasons; however, newer strategies in trials today and on the horizon encourage optimism. To help illustrate 'where we have been' with this fatal disease and 'where we are going' with contemporary studies, we include in this review a detailed history of Phase III clinical trials for GBM, with a final emphasis on exciting new treatment strategies that offer hope for future GBM therapy.
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Expert Opin Investig Drugs · Aug 2009
ReviewEGFR-directed therapies to treat non-small-cell lung cancer.
Lung cancer is the leading cause of cancer death in men and women. In 2008, in the US > 200,000 patients were diagnosed with lung cancer and > 160,000 died from their disease. Over 80% of lung cancers are of the non-small cell type, for which chemotherapy has demonstrated modest survival benefits at all stages of disease. ⋯ Downstream effects of EGFR dimerization and activation include cell proliferation, differentiation and angiogenesis, key events in the malignant process. Two main classes of drugs have been developed, small molecule tyrosine kinase inhibitors (TKIs) and monoclonal antibodies directed against the extracellular domain of the receptor. This review discusses clinical studies with several new therapies and the plans for drug development.
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Expert Opin Investig Drugs · Jul 2009
Comparative StudyTesofensine--a novel potent weight loss medicine. Evaluation of: Astrup A, Breum L, Jensen TJ, Kroustrup JP, Larsen TM. Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial. Lancet 2008;372:1906-13.
The incidence of obesity is increasing; this is of major concern, as obesity is associated with cardiovascular disease, stroke, type 2 diabetes, respiratory tract disease, and cancer. ⋯ It is encouraging that tesofensine 0.5 mg may cause almost double the weight loss observed with sibutramine or rimonabant. As tesofensine and sibutramine have similar pharmacological profiles, it would be of interest to compare the weight loss with tesofensine in a head-to-head clinical trial with sibutramine, to properly assess their comparative potency. Also, as teso fensine 0.5 mg increases heart rate, as well as increasing the incidence of adverse effects such as nausea, drug mouth, flatulence, insomnia, and depressed mode, its tolerability needs to be further evaluated in large Phase III clinical trials.
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The World Health Organization (WHO) report has predicted that major depression will become a key cause of illness-induced disability by the year 2020, second only to ischemic heart diseases. ⋯ There is an exciting future in the discovery of novel targets and target-specific agents for the management of major depression.