Drug Des Dev Ther
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Epidermal growth factor receptor (EGFR) tyrosine inhibitors were first approved for the treatment of non-small cell lung cancer (NSCLC) in 2003 in the US. Activating EGFR mutations were subsequently discovered in 2004, and heralded the era of molecular targeted therapy in NSCLC. The discovery of anaplastic lymphoma kinase (ALK) rearrangement in NSCLC in 2007 by two independent groups not only represents the first time ALK rearrangement has been discovered in common solid tumors but also represents another important milestone in the era of molecular targeted therapy in NSCLC. ⋯ Common adverse events of crizotinib include mild transient visual disorders, mild gastrointestinal toxicities, fatigue, rare alanine transaminase elevations, and even rarer pneumonitis (1.6%). Confirmatory trials comparing crizotinib with standard chemotherapy are ongoing. It took an unprecedented four years from the discovery of ALK rearrangement in NSCLC to the approval of crizotinib, the first ever ALK inhibitor, for the treatment of ALK-rearranged NSCLC.
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A recent explosion in the amount of cardiovascular risk and incipient, undetected subclinical cardiovascular pathology has swept across the globe. Nearly 70% of adult Americans are overweight or obese; the prevalence of visceral obesity stands at 53% and continues to rise. At any one time, 55% of the population is on a weight-loss diet, and almost all fail. ⋯ Of all agents available, rosuvastatin produces the greatest reduction in LDL-C, LDL-P, and improvement in apoA-I/apoB, together with a favorable safety profile. Several recent proposals and methods to lower cardiovascular risk are reviewed. A combination of approaches, such as the addition of lifetime risk, refinement of risk prediction, guideline compliance, novel treatments, improvement in adherence, and primordial prevention, including environmental and social intervention, will be necessary to lower the present high risk burden.
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Chagas disease must be treated in all its stages: acute, indeterminate, chronic, and initial and middle determinant chronic, due to the fact that DNA of the parasite can be demonstrated by PCR in chronic cases, where optical microscopy does not detect parasites. Nifurtimox (NF) and benznidazole (BNZ) are the drugs accepted to treat humans based upon ethical considerations and efficiency. However, both the drugs produce secondary effects in 30% of the cases, and the treatment must be given for at least 30-60 days. ⋯ In acute cases, 70% cure with NF and 75% with BNZ is achieved. In congenital cases, 100% cure is obtained if the treatment is performed during the first year of life. In chronic acquired cases, 20% cure and 50% improvement of the electrocardiographic changes are obtained with itraconazole.
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The clinical efficacy, different dosages, treatment schedules, and safety of azacitidine are reviewed. ⋯ Azacitidine is the first DNA hypomethylating agent approved by FDA for the treatment of myelodysplastic syndromes with demonstrated efficacy.
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Eltrombopag is one of a number of novel agents recently developed for use in the treatment of patients with immune thrombocytopenia (ITP). Rather than preventing destruction of platelets, these agents increase the production of platelets, presumably overwhelming the immune system resulting in normal platelet counts in individuals refractory to or dependent on other therapies. These treatments are well tolerated and in randomized controlled trials show an improvement in platelet counts and a reduction in bleeding in refractory patients. This article summarizes the development of this new class of drug and evaluates the safety and efficacy of eltrombopag in patients with ITP.