Expert opinion on pharmacotherapy
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Expert Opin Pharmacother · Feb 2014
EditorialAn aspirin a day? Aspirin use across a spectrum of risk: cardiovascular disease, cancers and bleeds.
Aspirin or acetylsalicylic acid (ASA) is commonly used in the general population for primary prevention of cardiovascular disease (CVD). Strong evidence supports the use of ASA in secondary prevention of CVD; however, for primary prevention, potential benefits are offset by potential harms (primarily major bleeds), with no benefit in overall mortality. ⋯ Finally, evidence supporting ASA use for cancer prevention is limited. Health care providers should be aware of the benefits and risks associated with ASA use in primary and secondary prevention and discuss these with their patients in the context of individual patient values and preferences.
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Expert Opin Pharmacother · Feb 2014
ReviewPalbociclib (PD 0332991) : targeting the cell cycle machinery in breast cancer.
The cyclin D-cyclin-dependent kinases 4 and 6 (CDK4/6)-retinoblastoma (Rb) pathway, governing the cell cycle restriction point, is frequently altered in breast cancer and is a potentially relevant target for anticancer therapy. Palbociclib (PD 0332991) , a potent and selective inhibitor of CDK4 and CDK6, inhibits proliferation of several Rb-positive cancer cell lines and xenograft models. ⋯ The combination of palbociclib with endocrine agents is a very promising treatment and Phase III clinical trials are ongoing to confirm its efficacy. Further, potentially useful combinations are those with drugs targeting mitogenic signaling pathways, such as HER2- and PI3K-inhibitors. Combination with chemotherapy seems more problematic, as antagonism has been reported in preclinical models. The identification of predictive factors, already explored in preclinical studies, must be further refined and validated in clinical trials.
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Expert Opin Pharmacother · Feb 2014
ReviewSelexipag for the treatment of pulmonary arterial hypertension.
Selexipag is a first-in-class orally available selective non-prostanoid IP receptor agonist. This review was based on a PubMed search and focuses on the potential role of selexipag in the treatment of pulmonary arterial hypertension (PAH). ⋯ The signal of a beneficial effect of selexipag on disease progression may become more robust for long term under prolonged exposure. Pending the GRIPHON trial results, selexipag could provide a convenient first-line prostacyclin treatment option for patients with PAH.
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Expert Opin Pharmacother · Feb 2014
Review Comparative StudyAxitinib for the treatment of advanced renal cell carcinoma.
Advanced understanding of the pathogenesis of renal cell carcinoma (RCC) has led to development and approval of several molecularly targeted therapies since 2005. Axitinib is a potent and selective inhibitor of vascular endothelial growth factor receptors 1, 2 and 3. In the randomized Phase III AXIS trial, axitinib significantly prolonged progression-free survival compared with sorafenib, respectively (6.7 vs 4.7 months; p < 0.0001), and improved objective response rate (19 vs 9%; p = 0.0001), resulting in its approval for advanced or metastatic RCC after failure of one systemic therapy. However, overall survival was similar with axitinib and sorafenib. Common adverse events associated with axitinib include diarrhea, hypertension and fatigue. ⋯ Axitinib is generally well-tolerated and provides definitive clinical benefits in patients with advanced or metastatic RCC as second-line therapy. However, as with other tyrosine kinase inhibitors of the same class, axitinib does not prolong overall survival; therefore, selection of second-line tyrosine kinase inhibitor therapy, including axitinib, must be carefully considered to maximize outcomes for each patient.
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Expert Opin Pharmacother · Feb 2014
ReviewMechanisms, treatment and prevention of cellular injury and death from delayed events after aneurysmal subarachnoid hemorrhage.
Subarachnoid hemorrhage (SAH) patients often develop brain injury as a result of a number of delayed complications, resulting in significant morbidity and mortality. Many of these complications arise due to delayed cerebral ischemia, which occurs secondary to the hemorrhage. ⋯ Multiple mechanisms are involved in the pathogenesis of the delayed insult after SAH. New drugs may need to target multiple pathways to injury. Trials aiming to treat complications after SAH could benefit from taking into account the multifactorial pathogenesis of delayed insults.