Drugs of today
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A multivesicular liposomal formulation of bupivacaine which can provide prolonged postsurgical pain relief has been developed. Two pivotal placebo-controlled phase III trials, one in hemorrhoidectomy and one in bunionectomy procedures, showed that wound infiltration of the suspension at the end of surgery could provide analgesia for up to 72 hours, reduce the amount of opiate rescue medications, the time to their first use and increase patient satisfaction. ⋯ S. health economic study showed benefits (versus patient-controlled analgesia) for the preparation in decreasing total opioid use, length of hospital stay and total hospital costs. Further larger studies are warranted, in particular using bupivacaine hydrochloride as the comparator.
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Advanced melanoma traditionally has had poor prognosis with limited, modestly effective and relatively toxic systemic treatment options like cytotoxic chemotherapy (dacarbazine) and immunomodulating agents (high-dose interleukin-2 and ipilimumab) which have response rates of 6-20%. With the identification of BRAF mutations found to be present in 50% of melanomas and the clinical success of serine/threonine-protein kinase B-raf inhibitors the prognostic landscape of melanoma has changed considerably. Vemurafenib and dabrafenib have been at the forefront of antimelanoma-targeted agents with a tolerable side effect profile and efficacy that compared well with the standard chemotherapy. ⋯ However, these agents are not curative and have a short life span primarily due to rapidly occurring drug resistance. More recently, mitogen-activated protein kinase kinase (MEK) inhibitors have been found to have strong anticancer activity independently as well as when combined with other agents like B-raf inhibitors due to their activity downstream of RAF. Preclinical data and limited clinical data suggest that MEK inhibitors may be a component of effective therapy for a broad spectrum of cancers with other oncogenic drivers.