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Fermiano M.,University of Campinas | Bergsbaken J.,University of Wisconsin - Madison | Kolesar J.M.,University of Wisconsin - Madison | Kolesar J.M.,Carbone Comprehensive Cancer Center
American Journal of Health-System Pharmacy | Year: 2014

Purpose. The pharmacology, pharmacokinetics, clinical efficacy, safety, dosage, administration, and current role in therapy of a recently approved agent for controlling methotrexate toxicity are reviewed. Summary. Glucarpidase is a bacterial enzyme useful in reversing toxicity induced by the widely used antineoplastic agent methotrexate. Glucarpidase gained U.S. marketing approval in 2012 for reducing serum methotrexate concentrations greater than 1 μM/L in patients with delayed methotrexate clearance due to impaired renal function. In clinical trials, glucarpidase has been administered to a total of 3887 patients receiving high-dose methotrexate (i.e., doses of ≥500 mg/m2), including pediatric patients. Patients treated with glucarpidase in addition to standard supportive care (hydration, urinary alkalization, leucovorin rescue, and, in some cases, hemodialysis) had a mean reduction in serum methotrexate levels of greater than 88%, with reductions occurring in a median of 15 minutes; however, up to 4.4% of adult patients and up to 6% of pediatric patients in clinical trial cohorts died despite glucarpidase use, suggesting the agent might not confer a survival advantage over supportive care alone. Glucarpidase is well tolerated; the most common adverse effects are flushing, nausea, vomiting, hypotension, and headache, which are typically grade 1 or 2 in severity and resolve without intervention. Conclusion. Glucarpidase is a well-tolerated and effective treatment for reducing serum methotrexate concentrations greater than 1 μM/ L in patients with impaired renal function. While there are few adverse effects associated with treatment, there may be little or no impact on methotrexate-associated mortality. Copyright © 2014 American Society of Health-System Pharmacists Inc. All rights reserved. Source


Timm A.,University of Wisconsin - Madison | Kolesar J.M.,University of Wisconsin - Madison | Kolesar J.M.,Carbone Comprehensive Cancer Center
American Journal of Health-System Pharmacy | Year: 2013

Purpose. The pharmacology, pharmacokinetics, clinical efficacy, safety, adverse effects, and dosage and administration of crizotinib in the management of non-small-cell lung cancer (NSCLC) are reviewed. Summary. Crizotinib (Xalkori, Pfizer Inc.) is a novel tyrosine kinase inhibitor approved for the treatment of patients with locally advanced or metastatic NSCLC who exhibit assay-confirmed mutations of the gene coding for anaplastic lymphoma kinase (ALK). The primary biochemical mechanism of crizotinib is to inhibit ALK expression, leading to increased cell proliferation and decreased apoptosis. Crizotinib is metabolized and excreted after O-dealkylation by cytochrome P-450 (CYP) isoenzyme 3A4/5; as crizotinib is also an inhibitor of CYP3A4/5, its use entails a high potential for drug interactions, including confirmed interactions with ketoconazole and rifampin that can alter crizotinib pharmacokinetics. A Phase I trial involving patients with ALK gene mutation-positive NSCLC demonstrated significant disease control with oral crizotinib use, including an overall eight-week response rate of 87% and an estimated six-month survival of 72%. At the standard dosage of 250 mg twice daily, crizotinib is well tolerated. In clinical trials to date, the most common grade 1 or 2 adverse events were nausea, diarrhea, vomiting, and visual disturbances; more severe toxicities included transaminase elevations (less than 7% of patients) and pneumonitis (less than 2% of patients). Hypogonadism leading to low testosterone levels appears to be universal among male patients treated with crizotinib. Conclusion. Crizotinib appears to be efficacious and well tolerated in patients with NSCLC and may have future potential applications in treating lymphomas and other cancers driven by ALK or c-MET gene mutations. Copyright © 2013, American Society of Health-System Pharmacists, Inc. All rights reserved. Source


Ahrens D.,Carbone Comprehensive Cancer Center | Jones N.,Carbone Comprehensive Cancer Center | Pfister K.,Wisconsin Tobacco Prevention and Control Program | Remington P.L.,University of Wisconsin - Madison
Wisconsin Medical Journal | Year: 2011

Background: Although public and media attention has focused on the federal role in the regulation of tobacco products, state government remains an important arena for changing tobacco control policies. Lobbying state officials by public health and the tobacco industry is a commonly used mechanism to influence public policy. Methods: Major bills of the 2007 - 2008 and 2009 - 2010 Wisconsin legislative sessions related to tobacco use regulation were analyzed by the hours engaged in lobbying and the estimated expenditures by supporters and opponents of tobacco control legislation in reports submitted to the Government Accountability Board. Results: In the 2007 - 2008 legislative session, anti-tobacco control organizations reported lobbying expenditures of more than $2 million (2627 hours) while opposing bills to raise tobacco excise taxes and enact smoke-free legislation; pro-tobacco control organizations reported lobbying expenditures of $623,000 (3997 hours) while supporting these bills. In the first 6 months of the 2009 session, anti-tobacco control groups spent $1.25 million (1472 hours) and pro-tobacco control groups spent $172,000 (1727 hours). Conclusion: In the 2007 - 2008 legislative session, the proposal to increase the tobacco tax by $1 per pack was passed. However, the smoke-free indoor air bill was defeated. Antitobacco control organizations outspent pro-tobacco control organizations by a margin of over 3:1. In 2009 anti-tobacco control groups outspent health groups by a ratio of 7:1. Legislation for smoke-free workplaces and an increase in the cigarette tax was enacted. However, funding for tobacco prevention and treatment programs was substantially reduced. Source

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