Expert opinion on pharmacotherapy
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Expert Opin Pharmacother · Jan 2016
ReviewRifaximin and eluxadoline - newly approved treatments for diarrhea-predominant irritable bowel syndrome: what is their role in clinical practice alongside alosetron?
Diarrhea-predominant irritable bowel syndrome (IBS-D) is a common functional gastrointestinal condition in which patients experience abdominal pain, diarrhea, bloating, cramps, flatulence, fecal urgency, and incontinence. ⋯ The rifaximin and eluxadoline clinical development programs for IBS-D have demonstrated significant improvement in IBS-D endpoints compared to placebo. Direct comparison of primary endpoint results from the alosetron, rifaximin, and eluxadoline pivotal trials is not possible; however, general estimates of efficacy can be made, and these demonstrate similar and significantly greater responses to 'adequate relief' and a composite endpoint of abdominal pain/stool form for each agent compared to placebo. With the recent approval in the United States of rifaximin and eluxadoline for IBS-D, how should clinicians employ these agents? We suggest that they be utilized sequentially, taking into consideration patient symptoms and severity, prior medical history, mode of action, cost, availability, managed care coverage, and adverse event profiles.
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In 2008, the Federal Drug Administration (FDA) required all new glucose-lowering therapies to show cardiovascular safety, and this applies to the dipeptidyl peptidase (DPP)-4 inhibitors ('gliptins'). At present, there is contradictory evidence on whether the gliptins increase hospitalizations for heart failure. ⋯ Despite the results of TECOS, debate over the effects of sitagliptin on the rates of hospitalizations for heart failure continues with some recent studies suggesting increased rates. Recently, empagliflozin (an inhibitor of sodium-glucose cotransporter 2) has been shown to reduce cardiovascular outcomes in subjects with type 2 diabetes, including the rates of hospitalization for heart failure. In our opinion, these positive findings with empagliflozin suggest that it should be prescribed in preference to the gliptins, including sitagliptin, unless any positive cardiovascular outcomes are reported for the gliptins.
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Expert Opin Pharmacother · Jan 2016
ReviewRociletinib, a third generation EGFR tyrosine kinase inhibitor: current data and future directions.
Major advances have been made since the discovery of driver mutations and their targeted therapies, especially in the treatment of patients with epidermal growth factor receptor (EGFR) mutations. Despite their initial efficacy in the majority of the patients with such driver mutations, all targeted therapies are limited by the eventual development of resistance mechanisms. ⋯ It is important to note that there are other 3(rd) generation EGFR TKIs with activity against T790M already approved by the US FDA (osimertinib) and many others in development. Future research will focus on figuring out which patients can benefit the most from a particular medication with minimal side effects, and further resistance mechanisms after rociletinib.
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Expert Opin Pharmacother · Jan 2016
ReviewCombination dabrafenib and trametinib in the management of advanced melanoma with BRAFV600 mutations.
In the 40-50% of advanced melanoma patients with tumors harboring BRAF V600E and V600 K mutations, BRAF inhibitors such as dabrafenib are a highly effective treatment. However, most patients develop resistance after several months on treatment. The addition of a MEK inhibitor, such as trametinib, to BRAF inhibition mitigates one key pathway of resistance, further increasing response rates and improving survival. ⋯ Combination therapy with dabrafenib and trametinib improves response rate, progression-free survival and overall survival when compared to dabrafenib or vemurafenib alone. The addition of trametinib to dabrafenib changes the adverse event profile, making hyperkeratosis and cutaneous squamous cell carcinomas less common but side effects such as fever and nausea more common. How dabrafenib/trametinib is best sequenced with other effective treatments such as immune checkpoint blockade remains uncertain.
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Expert Opin Pharmacother · Jan 2016
ReviewLanreotide for the treatment of gastroenteropancreatic neuroendocrine tumors.
The prevalence of gastropancreatic neuroendocrine tumors (GEP-NETs), a largely sporadically occurring group of neoplasms, has rapidly increased. NET diagnoses often occur late and entail treatment challenges; treatment beyond surgical resection is typically required. Somatostatin analogs (SSAs), the cornerstone of GEP-NET therapy, target somatostatin receptors on NET cell surfaces and can ameliorate NET-related symptoms and prevent tumor progression. ⋯ The role of SSAs in NET treatment was historically one of symptom management. Although this is a critical therapeutic component, ideal treatment would include prevention of tumor progression. As GEP-NETs are biologically diverse, progression prevention can be difficult, depending on primary tumor site and functional status. Recent data indicate that lanreotide significantly prolonged progression-free survival in metastatic GEP-NET patients. Practice patterns seem to be shifting toward using SSAs as first-line therapy. Response to SSAs has typically been categorized as either symptomatic or biochemical. However, SSA use to prevent tumor progression will lead to a new, objective response category based on tumor growth.