The recommended phase II dose of docetaxel combined with estramustine is 70 mg/m2 in MPT patients and 60 mg/m2 in EPT patients. This combination is active in men with androgen-independent prostate cancer.

Background-Increased myocyte loss and extracellular matrix (ECM) turnover are central mechanisms that contribute to pathological myocardial remodeling in chronic heart failure (HF). We tested the hypothesis that episodes of acute HF syndrome (AHFS) are associated with transient increases in markers of myocyte injury and ECM turnover beyond those observed in chronic stable HF. Methods and Results-Markers of myocyte injury and ECM turnover were assessed in 80 patients prospectively divided into 3 groups: AHFS (nϭ39); chronic stable systolic HF (nϭ21); and control subjects without HF (nϭ20). Myocyte injury was assessed by measuring plasma troponin I. ECM turnover was assessed by measuring plasma matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases, and procollagen N-terminal type I and procollagen type III N-terminal peptides. In the AHFS group, biomarkers were obtained (1) at the time of hospital admission for an episode of HF decompensation, (2) at the time of hospital discharge, and (3) several weeks after discharge in patients who had returned to a chronic stable compensated state. In patients with stable HF (versus non-HF controls), there was a small increase in troponin I and little or no difference in any marker of ECM turnover. In patients with AHFS, troponin I and 3 markers of ECM turnover (matrix metalloproteinases-2, tissue inhibitors of matrix metalloproteinases-1, and procollagen type III N-terminal peptides) were elevated (versus chronic stable HF), and all fell toward chronic HF levels in patients who returned to a compensated state. Conclusion-Episodes

Background Patients with heart failure (HF) develop metabolic derangements including increased adipokine levels, insulin resistance, inflammation and progressive catabolism. It is not known whether metabolic dysfunction and adipocyte activation worsen in the setting of acute clinical decompensation, or conversely, improve with clinical recovery. Methods and Results We assessed insulin resistance using HOMA-IR, and measured plasma levels of NT-proBNP, adiponectin, visfatin, resistin, leptin, and TNFα in 44 patients with acute decompensated HF (ADHF) due to left ventricular (LV) systolic dysfunction and again early (<1 week) and late (> 6 months) after clinical recovery; 26 patients with chronic stable HF; and 21 patients without HF. NT-proBNP was not increased in controls, mildly elevated in patients with stable HF, markedly elevated in patients with ADHF, and decreased progressively early and late after treatment. Compared to controls, plasma adiponectin, visfatin, leptin, resistin and TNFα were elevated in patients with chronic stable HF and increased further in patients with ADHF. Likewise, HOMA-IR was increased in chronic stable HF and increased further during ADHF. Adiponectin, visfatin and HOMA-IR remained elevated at the time of discharge from the hospital, but returned to chronic stable HF levels. Adipokine levels were not related to BMI in HF patients. HOMA-IR correlated positively with adipokines and TNFα in HF patients. Conclusions ADHF is associated with worsening of insulin resistance and elevations of adipokines and TNFα indicative of adipocyte activation. These metabolic abnormalities are reversible, but temporally lag behind the clinical resolution of decompensated HF.

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Introduction: The extracellular matrix (ECM) plays an active role in myocardial remodeling in heart failure (HF). Episodes of decompensation are associated with increased levels of neurohormones, inflammation and oxidative stress that are known to affect ECM regulation, and may contribute to progression of HF. We hypothesized that HF decompensation is associated with dysregulation of ECM turnover, as reflected by markers of degradation (matrix metalloproteinases [MMPs] and their tissue inhibitors [TIMPs]) and synthesis (pro-collagen N-terminal types I [PINP] and III [PIIINP]). Methods: Blood levels of MMP-2 and -9, TIMP-1, -2 and -4, and PI- and PIIINP were measured in 80 patients in 3 groups: 20 controls without HF, 21 patients with chronic stable systolic HF (no recent admission and no congestion by clinical examination), and 39 patients with acute HF decompensation, in whom measures were done on admission, at discharge, and chronically at least 2 months later. Results: In chronic stable HF, ECM markers were not increased vs. controls. In contrast, in patients with decompensated HF, MMP-2, TIMP-1 and PIIINP levels were increased (vs. stable HF or controls; Table ), while MMP-9, TIMP-2 and -4 or PINP were unchanged. Likewise, following effective therapy and return to clinical compensation (chronically but not at discharge) MMP-2, TIMP-1 and PIIINP levels returned to chronic stable HF levels, whereas MMP-9, TIMP-2 and -4 or PINP remained unchanged. Conclusion: A transient ECM dysregulation occurs during acute episodes of HF decompensation and may contribute to adverse ventricular remodeling. While HF decompensation is associated with certain markers of degradation and synthesis (MMP-2, TIMP-1 and PIIINP), other markers (MMP-9, TIMP-2 and -4 or PINP) are unchanged, suggesting selective pattern of ECM activation. The observation that matrix turnover is increased in decompensated but not stable HF may have implication for the timing of anti-remodeling therapy. ECM markers in controls, stable and decompensated HF