Expert opinion on investigational drugs
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Expert Opin Investig Drugs · May 2011
EditorialFrom targeted therapy in ovarian cancer to personalizing therapy for ovarian cancer.
Epithelial ovarian carcinoma (EOC) is the most important cause of gynecological cancer-related mortality in Western societies. The majority of patients with ovarian cancer present with advanced disease, and in this group of patients, the median survival time is only 3 years. ⋯ Two strategies have emerged with promising results: poly ADP-ribose polymerase enzyme (PARP) inhibitors and targeting angiogenesis. The challenge remains to develop a convenient and accurate method to identify patients likely to benefit from targeted therapy.
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Pulmonary hypertension (PH) is a severe condition with a poor prognosis despite recent treatment advances. Therapies with new mechanisms of action are needed. ⋯ Cyclic guanosine monophosphate (cGMP) is an important mediator of the preferential perfusion of well-ventilated regions throughout the lung. Drugs that increase cGMP levels could promote pulmonary vasorelaxation while maintaining optimal gas exchange. cGMP is generated by sGC, which can be stimulated by nitric oxide (NO). Riociguat stimulates sGC independently of NO and increases the sensitivity of sGC to NO, resulting in increased cGMP levels. Results to date suggest rapid, potent and prolonged efficacy and good tolerability in different types of PH. Phase III clinical trials are evaluating the long-term safety and clinical effectiveness of riociguat in pulmonary arterial hypertension (PAH) and chronic thromboembolic PH. Riociguat has the potential to become an important drug for the treatment of patients with PH.
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Expert Opin Investig Drugs · Apr 2011
ReviewInvestigational factor Xa inhibitors for thrombosis and acute coronary syndromes.
A number of new oral anticoagulant drugs that selectively and directly inhibit factor Xa (FXa) appear as promising alternatives to the existing anticoagulant agents. These compounds present a convenient route of administration with predictable pharmacokinetics and pharmacodynamics that allow fixed dosing regimens without requiring coagulation monitoring. Rivaroxaban is the first of this new class of drugs that was approved for the prevention of venous thromboembolism (VTE) after elective total hip replacement or total knee replacement surgery in the EU, Canada and several other countries. Clinical trials with rivaroxaban in patients with acute VTE and in patients with atrial fibrillation have been recently completed. Numerous other compounds are under different developing stages (apixaban, edoxaban, otamixaban, LY517717, PRT-054021, YM150). ⋯ Undoubtedly, these new drugs will offer several advantages over the previous compounds, but a number of issues still require some attention during the phase of translation from clinical trials into daily clinical practice.
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Expert Opin Investig Drugs · Mar 2011
Comment Multicenter Study Controlled Clinical TrialCystic fibrosis transmembrane regulator potentiators as promising cystic fibrosis therapies.
Several types of mutations in the cystic fibrosis transmembrane regulator (CFTR) gene lead to abnormal CFTR protein and alterations of chloride and sodium transmembrane transportation in cystic fibrosis (CF). Some investigational compounds such as VX-770 can improve CFTR protein function. ⋯ VX-770 is able to improve chloride and sodium transportation and has a good safety profile. Although such compounds have limited therapeutic targeting potential, preliminary results show great promise in the context of CF therapy.
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Expert Opin Investig Drugs · Mar 2011
ReviewThe use of vasopressin receptor antagonists in hyponatremia.
Considerable data have recently characterized hyponatremia as fairly common in the intensive care and general hospital settings. Moreover, mounting evidence suggests the association of mild degrees of hyponatremia with untoward neurocognitive and musculoskeletal outcomes. A key development in our ability to treat hyponatremia was the introduction and approval of aquaretics (vaptans). These vasopressin receptor antagonists work by increasing electrolyte-free water excretion and thus raising serum sodium concentration. ⋯ Vaptans are likely to play an important role in treating hyponatremia, given their clinical efficacy and tolerability. High cost remains an impediment for vaptans, and more studies are needed to further define their best use in hyponatremic patients.