Expert opinion on emerging drugs
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Sepsis remains a major cause of death in intensive care units. Despite an intense research, a new drug that is effective in reducing mortality in sepsis is still awaited. ⋯ New licensed antibiotics will offer the opportunity to refine the treatment choices. Direct hemoperfusion using polymyxin B-immobilized fiber column may be an option in sepsis due to Gram-negative bacilli. Among non-antibiotic drugs, new ongoing studies will clarify the role of drotrecogin alfa (activated) and low dose hydrocortisone. The modulation of monocytic human leukocyte antigen-DR seems the most prominent treatment. The use of cardiovascular drugs requires well-conducted clinical trials. The regulation of high mobility group box 1, adenosine blockade or correction of the impaired energy production is still at the experimental level.
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Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide. Although patients with early-stage disease have a good prognosis, there has been no effective therapy available for those with advanced disease. Despite the death risk of patients with advanced HCC being reduced with sorafenib therapy, many patients eventually turn out to be refractory to this therapy. Thus, treatment of HCC remains an urgent health concern. ⋯ Understanding the mechanisms of action, safety and efficacy of these new agents and new methods of combining these drugs may help prolong overall survival of patients with HCC and reduce disease recurrence after surgery or ablative therapies.
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Small-cell lung cancer (SCLC) is a rapidly progressing tumor in which chemotherapy has a limited impact on survival. Unfortunately, little progress has been made in the medical management of SCLC during the last 30 years, which is best exemplified by the fact that standard first-line chemotherapy has remained platinum-based over time. On the other hand, improvements in survival have been obtained only with the introduction of innovative radiation strategies such as accelerated hyperfractionation to the thorax for limited-stage disease and prophylactic cranial irradiation for both limited- and extensive-stage disease. ⋯ In this review, we address the most promising agents under clinical evaluation, discussing both novel chemotherapeutic agents and targeted agents. Particularly, amrubicin, a fully synthetic anthracycline, is a very active agent for SCLC, and ongoing Phase III trials are evaluating this agent either in the first-line setting of extensive-stage or relapsed disease. Among targeted agents, anti-angiogenic strategies and Bcl-2 inhibitors represent the most promising approaches, and they are being specifically tested in combination with and/or as maintenance therapy after first-line platinum-based chemotherapy.
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This review summarizes promising approaches for the treatment of traumatic brain injury (TBI) that are in either preclinical or clinical trials. ⋯ Nearly all Phase II/III clinical trials in neuroprotection have failed to show any consistent improvement in outcome for TBI patients. The next decade will witness an increasing number of clinical trials that seek to translate preclinical research discoveries to the clinic. Promising drug- or cell-based therapeutic approaches include erythropoietin and its carbamylated form, statins, bone marrow stromal cells, stem cells singularly or in combination or with biomaterials to reduce brain injury via neuroprotection and promote brain remodeling via angiogenesis, neurogenesis, and synaptogenesis with a final goal to improve functional outcome of TBI patients. In addition, enriched environment and voluntary physical exercise show promise in promoting functional outcome after TBI, and should be evaluated alone or in combination with other treatments as therapeutic approaches for TBI.
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Expert Opin Emerg Drugs · Dec 2008
ReviewEmerging tocolytics: challenges in designing and testing drugs to delay preterm delivery and prolong pregnancy.
The global rate of preterm delivery (before 37 completed weeks of pregnancy) is increasing and there are no effective means available to prevent this rise. Prematurity is the principal cause of neonatal mortality and a major cause of pediatric morbidity and long-term disability. Current strategies to prolong pregnancy are based on inhibiting the mechanisms that effect uterine smooth muscle (myometrium) contractions in women who are in preterm labor. ⋯ Again, it may be possible to use existing drugs for pregnancy maintenance. Several financial and practical barriers exist for developing completely new drugs to delay labor. Designing clinical trials to test tocolytics is complicated, as the health of two patients must be considered and the nature of preterm birth and its outcomes are different at early preterm labor (< 28 weeks) and late preterm labor (34 - 36 weeks).