Randomized phase III study of docetaxel compared with paclitaxel in metastatic breast cancer.

PURPOSE: This randomized, controlled, multicenter, open-label, phase III study compared docetaxel versus paclitaxel in patients with advanced breast cancer that had progressed after an anthracycline-containing chemotherapy regimen. PATIENTS AND METHODS: Patients (n = 449) were randomly assigned to receive either docetaxel 100 mg/m2 (n = 225) or paclitaxel 175 mg/m2 (n = 224) on day 1, every 21 days until tumor progression, unacceptable toxicity, or withdrawal of consent. RESULTS: In the intent-to-treat population, both the median overall survival (OS, 15.4 v 12.7 months; hazard ratio [HR], 1.41; 95% CI, 1.15 to 1.73; P = .03) and the median time to progression (TTP, 5.7 months v 3.6 months; HR, 1.64; 95% CI, 1.33 to 2.02; P < .0001) for docetaxel were significantly longer than for paclitaxel, and the overall response rate (ORR, 32% v 25%; P = .10) was higher for docetaxel. These results were confirmed by multivariate analyses. The incidence of treatment-related hematologic and nonhematologic toxicities was greater for docetaxel than for paclitaxel; however, quality-of-life scores were not statistically different between treatment groups over time. CONCLUSION: Docetaxel was superior to paclitaxel in terms of OS and TTP. ORR was higher for docetaxel. Hematologic and nonhematologic toxicities occurred more frequently in the docetaxel group. The global quality-of-life scores were similar for both agents over time.     

Endothelin antagonists in hypertension and kidney disease

The endothelin (ET) system seems to play a pivotal role in hypertension and in proteinuric kidney disease, including the micro- and macro-vascular complications of diabetes. Endothelin-1 (ET-1) is a multifunctional peptide that primarily acts as a potent vasoconstrictor with direct effects on systemic vasculature and the kidney. ET-1 and ET receptors are expressed in the vascular smooth muscle cells, endothelial cells, fibroblasts and macrophages in systemic vasculature and arterioles of the kidney, and are associated with collagen accumulation, inflammation, extracellular matrix remodeling, and renal fibrosis. Experimental evidence and recent clinical studies suggest that endothelin receptor blockade, in particular selective ET_AR blockade, holds promise in the treatment of hypertension, proteinuria, and diabetes. Concomitant blockade of the ET_B receptor is not usually beneficial and may lead to vasoconstriction and salt and water retention. The side-effect profile of ET receptor antagonists and relatively poor antagonist selectivity for ET_A receptor are limitations that need to be addressed. This review will discuss what is currently known about the endothelin system, the role of ET-1 in the pathogenesis of hypertension and kidney disease, and summarize literature on the therapeutic potential of endothelin system antagonism.     

Capitellum excision: Mechanical implications and clinical consequences

Controversy exists regarding the optimal treatment of isolated fractures of the capitellum that are not amenable to open reduction and internal fixation. Excision of the capitellum could result in instability of the elbow, though only limited the clinical or laboratory evidence exists to support this outcome. The aim of our study was to determine if capitellum excision leads to significant instability by measuring the relative change in varus–valgus displacement of the elbow. The varus–valgus displacement was recorded in 11 cadaveric elbows before and after isolated excision of the capitellum. Specimens were testing in varus‐loaded and valgus‐loaded positions with and without a 1 kg weight on the forearm. The varus–valgus displacement at the elbow was measured using a 3D motion capture system. Capitellum excision did not significantly change varus–valgus displacements in either the adducted, varus, or valgus position of the elbow (p = 0.80, p = 0.28, p = 0.51). Furthermore, the addition of the 1 kg external functional load to the forearm did not produce a significant change in the varus and valgus loaded positions (p = 0.16, p = 0.36). Our results demonstrate that excision of the capitellum in the setting of intact ligamentous structures does not result in significant instability in either the adducted varus loaded or valgus loaded positions of the elbow. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:346–350, 2014.