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Rizzo J.D.,Medical College of Wisconsin | Brouwers M.,McMaster University | Hurley P.,American Society of Clinical Oncology | Seidenfeld J.,American Society of Clinical Oncology | And 9 more authors.
Blood | Year: 2010

Purpose: To update American Society of Hematology/American Society of Clinical Oncology recommendations for use of erythropoiesis-stimulating agents (ESAs) in patients with cancer. Methods: An Update Committee reviewed data published between January 2007 and January 2010. MEDLINE and the Cochrane Library were searched. Results: The literature search yielded one new individual patient data analysis and four literature-based metaanalyses, two systematic reviews, and 13 publications reporting new results from randomized controlled trials not included in prior or new reviews. Recommendations: For patients undergoing myelosuppressive chemotherapy who have a hemoglobin (Hb) level less than 10 g/dL, the Update Committee recommends that clinicians discuss potential harms (eg, thromboembolism, shorter survival) and benefits (eg, decreased transfusions) of ESAs and compare these with potential harms (eg, serious infections, immune-mediated adverse reactions) and benefits (eg, rapid Hb improvement) of RBC transfusions. Individual preferences for assumed risk should contribute to shared decisions on managing chemotherapy-induced anemia. The Committee cautions against ESA use under other circumstances. If used, ESAs should be administered at the lowest dose possible and should increase Hb to the lowest concentration possible to avoid transfusions. Available evidence does not identify Hb levels ≥ 10 g/dL either as thresholds for initiating treatment or as targets for ESA therapy. Starting doses and dose modifications after response or nonresponse should follow US Food and Drug Administration-approved labeling. ESAs should be discontinued after 6 to 8 weeks in nonresponders. ESAs should be avoided in patients with cancer not receiving concurrent chemotherapy, except for those with lower risk myelodysplastic syndromes. Caution should be exercised when using ESAs with chemotherapeutic agents in diseases associated with increased risk of thromboembolic complications. Table 1 lists detailed recommendations. Copyright © 2010 American Society of Hematology and American Society of Clinical Oncology. All rights reserved.

Wang H.,Albany Medical College | Jiang M.,Vanderbilt University | Cui H.,Albany Medical College | Chen M.,Columbia College at South Carolina | And 5 more authors.
Molecular and Cellular Biology | Year: 2012

Activating transcription factor 3 (ATF3) is a common mediator of cellular stress response signaling and is often aberrantly expressed in prostate cancer. We report here that ATF3 can directly bind the androgen receptor (AR) and consequently repress AR-mediated gene expression. The ATF3-AR interaction requires the leucine zipper domain of ATF3 that independently binds the DNA-binding and ligand-binding domains of AR, and the interaction prevents AR from binding to cisacting elements required for expression of androgen-dependent genes while inhibiting the AR N- and C-terminal interaction. The functional consequences of the loss of ATF3 expression include increased transcription of androgen-dependent genes in prostate cancer cells that correlates with increased ability to grow in low-androgen-containing medium and increased proliferative activity of the prostate epithelium in ATF3 knockout mice that is associated with prostatic hyperplasia. Our results thus demonstrate that ATF3 is a novel repressor of androgen signaling that can inhibit AR functions, allowing prostate cells to restore homeostasis and maintain integrity in the face of a broad spectrum of intrinsic and environmental insults. © 2012, American Society for Microbiology.

Bennett C.L.,Columbia College at South Carolina
Cleveland Clinic Journal of Medicine | Year: 2011

Methods developed by the Southern Network on Adverse Reactions project, the only state-funded pharmacovigilance program in the nation, are invaluable in identifying rare and serious drug events and in disseminating related safety reports quickly throughout the medical community. An important discovery was identifi cation and reporting of an association of rituximab and progressive multifocal leukoencephalopathy (PML) in patients without human immunodefi ciency virus (HIV). A recent investigation identifi ed 57 patients with rituximab-associated PML, including bone marrow samples, brain biopsies, and autopsy materials from patients with lymphoma and PML who tested positive for JC virus. The investigation identifi ed an association of rituximab-chemotherapy administration and PML, although a causal relationship remains an area of active investigation. Additional investigations evaluated the epidemiology of PML in the oncology setting before and after the introduction of rituximab for lymphoma treatment. Focused analyses investigated risk factors for development of this rare complication. Further studies are needed to investigate the pathophysiology, epidemiology, and risk factors for PML developing among HIV-negative cancer patients who receive rituximab and chemotherapy.

Hawes E.M.,University of North Carolina at Chapel Hill | Maxwell W.D.,Columbia College at South Carolina | White S.F.,Sullivan University | Mangun J.,University of North Carolina at Chapel Hill | Lin F.-C.,University of North Carolina at Chapel Hill
Journal of Primary Care and Community Health | Year: 2014

Purpose: Medication errors related to hospital discharge result in rehospitalization and emergency department (ED) visits, yet no systematic approach has been implemented nationally to decrease these medication errors. Pharmacist involvement during postdischarge transitions of care may be an important strategy to prevent and correct medication discrepancies and reduce costly rehospitalization and ED visits. Methods: This prospective, randomized, open-label, pilot study evaluated the effect of a pharmacy clinic visit focused on medication reconciliation and patient education after hospital discharge on the incidence of rehospitalization and ED visits and the resolution of medication discrepancies. Results: Of the 61 subjects included in the study, 33 (54%) had medication discrepancies identified at discharge. Fifty percent of medication discrepancies were resolved in subjects randomized to the pharmacist intervention arm compared with 9.5% in the usual care arm (P =.015). Patients randomized to the intervention arm had significantly lower rates of the primary composite outcome of 30-day rehospitalization and ED visits compared with the usual care arm (0% vs 40.5%, P <.001). Conclusion: A pharmacist-driven intervention focused on patient education and medication reconciliation after discharge improved medication use and reduced health care resource utilization in this pilot study. © The Author(s) 2013.

Jarkowski A.,University of Rochester | Norris L.A.,Columbia College at South Carolina | Trinh V.A.,University of Houston
Annals of Pharmacotherapy | Year: 2014

Objective: To examine the current controversies and discuss consensus recommendations regarding treatment sequencing and the role of BRAF inhibitor at disease progression. Data Source: An English-language literature search of MEDLINE/PubMed (1966-May 2014), using the keywords advanced melanoma, ipilimumab, cytotoxic T-lymphocyte antigen 4, dabrafenib, vemurafenib, BRAF inhibitor, trametinib, MEK inhibitor, and treatment sequencing was conducted. Data were also obtained from package inserts, meeting abstracts, and clinical registries. Study Selection and Data Extraction: All relevant published articles and abstracts on ipilimumab, vemurafenib, dabrafenib, and trametinib were reviewed. Clinical trial registries and meeting abstracts were used for ongoing studies. Data Synthesis: The availability of new agents has made therapy selection more complex. Immunotherapy supporters reason that immunotherapy offers the best chance for long-term benefit and does not compromise the antitumor activity of subsequent BRAF inhibitors. Targeted therapy advocates rely on the high probability and rapid onset of response to BRAF inhibitors. Currently, there is insufficient evidence regarding the role of BRAF inhibitor at disease progression. Conclusions: Therapy should be individualized based on patient- and disease-specific factors. Immunotherapy represents the best option for durable remission; however, targeted therapy is more appropriate for patients who are symptomatic or have rapidly growing tumors. The novel therapies have also demonstrated meaningful intracranial activity; thus, the presence of brain metastases should be taken into consideration in selecting therapy. Limited data exist about the continuation of BRAF inhibitors after therapeutic failure. Active research is ongoing to define the best option for patients with BRAF inhibitor refractory disease. © The Author(s) 2014.

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