BACKGROUND: For first-line therapy options for advanced renal cell carcinoma (RCC), clinical trials have demonstrated similar efficacy for pazopanib and sunitinib as well as differing side-effect profiles, which may affect patient persistence in self-administration of these oral medications. However, the treatment patterns of each drug in real-world clinical practice, as opposed to the controlled environment of a trial, have not been directly compared.
Metal template synthesis is a useful methodology to make sophisticated macromolecular architectures because of the variety of metal ion coordination. To use metal template methodology, chelating functionalities should be introduced to macromolecules before complexation. In this article, we demonstrate the click‐to‐chelate approach to install chelating functionality to polystyrene (PS) and complexation with Ru(II) ions to form 3‐arm and 4‐arm star‐branched PS Ru(II) complexes. Azide‐terminated PS (PS‐N3) was readily prepared by atom transfer radical polymerization using 1‐bromoethylbenzene as an initiator followed by substitution of bromine by an azide group. The Cu(I)‐catalyzed 1,3‐dipolar cycloaddition of PS‐N3 with 2‐ethynylpyridine or 2,6‐diethynylpyridine affords 2‐(1H‐1,2,3‐triazol‐4‐yl)pyridine (PS‐tapy) or 2,6‐bis(1H‐1,2,3‐triazol‐4‐yl)pyridine (PS‐bitapy) ligands bearing one or two PS chains at the first‐position of the triazole rings. Ru(II) complexes of PS‐tapy and PS‐bitapy were prepared by conventional procedure. The number‐averaged molecular weights (Mns) of these complexes were determined to be 6740 and 10,400, respectively, by size exclusion chromatography using PS standards. These Mn values indicated the formation of 3‐arm and 4‐arm star‐branched PS Ru(II) complexes [Ru(PS‐tapy)3](PF6)2 and [Ru(PS‐bitapy)2](PF6)2 on the basis of the Mn values of PS‐tapy (2090) and PS‐bitapy (4970). The structures of these complexes were also confirmed by UV–vis spectroscopy and X‐ray crystallography of the Ru(II) complexes [Ru(Bn‐tapy)3](PF6)2 and [Ru(Bn‐bitapy)2](PF6)2, which bear a benzyl group instead of a PS chain. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011
IntroductionLittle is known about real-world use of small molecule kinase inhibitors (SMKI) for advanced thyroid cancer in the United States. This study examined prescribing patterns of SMKI agents recommended by the National Comprehensive Cancer Center (NCCN).MethodsThis retrospective study used a national health insurance database to identify patients diagnosed with thyroid cancer during 1/1/2006–6/30/2016 and with prescription claims for NCCN-recommended SMKI during 1/1/2010–5/31/2016 whose first claim date was the index date. Inclusion also required continuous enrollment in a health plan for 3 months pre-index (baseline) and ≥ 1 month post-index (follow-up) with no claims for SMKI during baseline. Lines of therapy (LOT) were defined by the date of SMKI claims and days of drug supply. Median time to SMKI discontinuation in each LOT was estimated by Kaplan–Meier method.ResultsThe study included 217 patients. During follow-up (mean duration 499.0 days), 35.5% of patients (n = 77) received a second or later LOT; among patients with ≥ 12 months follow-up after first LOT (LOT1) initiation, 53.1% (n = 60) received a second or later LOT. Median treatment duration was 5.0 months for LOT1 and 5.1 months for LOT2. Over the entire follow-up period (2010–2016), sorafenib was the most common regimen in LOT1 (36.9% of patients) and LOT2 (24.7%) followed by sunitinib and levantinib (13.4% each) in LOT1 and sunitinib (19.5%) in LOT2. Starting in 2015, the year lenvatinib was approved for differentiated thyroid cancer, lenvatinib was the most common first-line regimen among patients initiating LOT1 in 2015 (43.4%) and 2016 (66.7%).ConclusionSorafenib was the most common first-line agent during 2010–2014 but was supplanted by lenvatinib starting in 2015. Approximately 36–53% of patients received a second-line treatment. Median treatment duration results suggested potential benefit of SMKI in second-line therapy. SMKI treatment after first-line failure may be considered for appropriately selected patients.FundingEisai, Inc. (Woodcliff Lake, NJ).
Lynch Syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC), is the most common form of inherited colorectal cancer, however, its identification still presents a challenge for health care providers. Clinically-based guidelines have been used as the basis for Lynch Syndrome screening in colorectal cancer patient populations. More recently, it has been argued that universal molecular testing strategies should be implemented to increase the selection of patients who should get germline testing for Lynch Syndrome. In this issue of AJG, Julie et al compare the performance of clinical guidelines with a molecular strategy based on universal microsatellite instability (MSI) testing for identifying patients with Lynch Syndrome from among 214 unselected, newly diagnosed CRC patients. The study highlights the need for a systematic approach to identify patients with Lynch Syndrome so that they and their relatives can be targeted for appropriate clinical management.
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