Drug and Alcohol Rehabilitation: Safety and Efficacy of Cabazitaxel in the Docetaxel-Treated Patients With Hormone-Refractory Prostate Cancer.

Safety and efficacy of cabazitaxel in the docetaxel-treated patients with hormone-refractory prostate cancer.

Filed under: Drug and Alcohol Rehabilitation

Clin Med Insights Oncol. 2013; 7: 1-12
Calcagno F, Nguyen T, Dobi E, Villanueva C, Curtit E, Kim S, Montcuquet P, Kleinclauss F, Pivot X, Thiery-Vuillemin A

Prostate cancer (PC) is one of the most common cancers and is a leading cause of death. Its initial growth is dependent on androgens; most patients show an initial response to hormonal therapy but will experience disease progression when PC becomes resistant to castration. In 2004, two key randomized controlled trials demonstrated a benefit for docetaxel-based regimens in the treatment of men with castration-resistant prostate cancer (CRPC). Cabazitaxel (XRP6258, TXD258, and RPR116258A), a tubulin-binding taxane drug as potent as docetaxel in cell lines, was the first treatment able to prolong survival for metastatic CRPC in the post-docetaxel setting. This review describes pharmacologic parameters of this agent followed by a review of clinical trials involving cabazitaxel. Other available treatments and the place of cabazitaxel in metastatic CRPC setting are discussed.
HubMed – drug

Metabolomics coupled with proteomics advancing drug discovery towards more agile development of targeted combination therapies.

Filed under: Drug and Alcohol Rehabilitation

Mol Cell Proteomics. 2013 Jan 29;
Wang X, Zhang A, Wang P, Sun H, Wu G, Sun W, Lv H, Jiao G, Xu H, Yuan Y, Liu L, Zou D, Wu Z, Han Y, Yan G, Dong W, Wu F, Dong T, Yu Y, Zhang S, Wu X, Tong X, Meng X

To enhance therapeutic ef?cacy and reduce adverse effects of traditional Chinese medicine (TCM), practitioners often prescribe a combination of plant species and/or minerals called formulae. Unfortunately, the working mechanisms of most of these compounds are difficult to determine and thus remain unknown. In an attempt to address the benefits of formulae based on current biomedical approaches, we analyzed the components of Yinchenhao Tang (YCHT), a classical formula and has been shown to be clinically effective for treating hepatic injury (HI) syndrome. The three principal components of YCHT are Artemisia annua L., Gardenia jasminoids Ellis, and Rheum Palmatum L., whose major active ingredients are 6,7-dimethylesculetin (D), geniposide (G) and rhein (R), respectively. To determine the mechanisms that underlie this formula, we conducted a systematic analysis of the therapeutic effects of the DGR compound using immunohistochemistry, biochemistry, metabolomics and proteomics. Here, we report that the DGR combination exerts a more robust therapeutic effect than any one or two of the three individual compounds by hitting multiple targets in a rat model of HI. Thus, DGR synergistically causes intensi?ed dynamic changes in metabolic biomarkers, regulates molecular networks through target proteins, has a synergistic/additive effect and activates both intrinsic and extrinsic pathways.
HubMed – drug

Rapid Detection of Antibiotic Resistant Organism Carriage for Infection Prevention.

Filed under: Drug and Alcohol Rehabilitation

Clin Infect Dis. 2013 Jan 29;
Diekema DJ, Pfaller MA

Rapid detection of multiple-drug resistant organism (MDRO) carriers could help reduce MDRO infections by allowing for faster institution of prevention measures. However, improving the turnaround time (TAT) of a test requires attention to more than the analytic TAT, and will only occur if post-analytic processes (test reporting and care interventions) are also rapid and efficient. Obstacles to rapid MDRO test development include complex evolving resistance mechanisms, performance directly on mixed samples (e.g. nares, stool), and adaptation of new methods for routine clinical diagnostic use. Existing data to support the clinical utility of rapid detection (versus standard culture methods) are scant. For these reasons, rapid detection of MDRO carriers remains a work-in-progress. Future efforts should be on developing rapid tests to detect multiple-drug resistant gram negative rods, particularly those harboring ?-lactamases, and on performing clinical trials to determine how best to incorporate rapid detection of MDRO carriage into HAI prevention efforts.
HubMed – drug

SWIFT: Prospective 48 Week Study to Evaluate Efficacy and Safety of Switching to Emtricitibine/Tenofovir from Lamivudine/Abacavir in Virologically Suppressed HIV-1 Infected Patients on a Boosted Protease Inhibitor Containing Antiretroviral Regimen.

Filed under: Drug and Alcohol Rehabilitation

Clin Infect Dis. 2013 Jan 29;
Campo R, Dejesus E, Bredeek UF, Henry K, Khanlou H, Logue K, Brinson C, Benson P, Dau L, Wang H, White K, Flaherty J, Fralich T, Guyer B, Piontkowsky D

Background.?In the US, FTC/TDF is a preferred NRTI backbone with 3TC/ABC as a commonly used alternative. For HIV infected patients virologically suppressed on a boosted PI+3TC/ABC regimen, the merits of switching to FTC/TDF as the NRTI backbone are unknown.Methods.?SWIFT was a prospective, randomized, open-label 48-week study to evaluate efficacy and safety of switching to FTC/TDF. Subjects receiving 3TC/ABC+PI+RTV with HIV RNA <200 c/mL?3 months were randomized to continue 3TC/ABC or switch to FTC/TDF. The primary endpoint was time to loss of virologic response (TLOVR) with non-inferiority measured by delta of 12%. Virologic failure (VF) was defined as confirmed rebound or the last HIV RNA measurement on study drug?200 c/mL.Results.?311 subjects were treated in this study (155 to PI+RTV+FTC/TDF, 156 to PI+RTV+3TC/ABC). Baseline characteristics were similar between the arms: 85% males, 28% African Americans, median age 46 years, and median CD4 532 cells/mm(3). By TLOVR through Week 48, switching to FTC/TDF was non-inferior compared to continued 3TC/ABC (86.4% vs. 83.3%, treatment difference 3.0% (95% CI -5.1% to 11.2%). Fewer subjects on FTC/TDF experienced VF (3 vs. 11; p=0.034). FTC/TDF showed greater declines in fasting LDL, total cholesterol (TC), and triglycerides (TG) with significant declines in LDL and TC beginning at Week 12 with no TC/HDL ratio change. Switching to FTC/TDF showed improved NCEP thresholds for TC and TG and improved 10-year Framingham TC calculated scores. Decreased eGFR was observed in both arms with a larger decrease in the FTC/TDF arm.Conclusions.?Switching to FTC/TDF from 3TC/ABC maintained virologic suppression, had fewer VFs, improved lipid parameters and Framingham scores, but decreased eGFR. HubMed – drug

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