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neutropenic regimen

Maro Ohanian, Ana Tari Ashizawa, Guillermo Garcia-Manero, Naveen Pemmaraju, Tapan Kadia, Elias Jabbour, Farhad Ravandi, Gautam Borthakur, Michael Andreeff, Marina Konopleva, Miranda Lim, Sherry Pierce, Susan O'Brien, Yesid Alvarado, Srdan Verstovsek, William Wierda, Hagop Kantarjian, Jorge Cortes
BACKGROUND: Activating mutations of tyrosine kinases are common in leukaemias. Oncogenic tyrosine kinases use the growth factor receptor-bound protein 2 (Grb2) for signal transduction, leading to activation of mitogen-activated protein kinase (MAPK) 1 and MAPK3 (ERK2 and ERK1). We hypothesised that inhibition of Grb2 would suppress ERK1 and ERK2 activation and inhibit leukaemia progression. To inhibit Grb2, a liposome-incorporated antisense oligodeoxynucleotide that blocks Grb2 protein expression, BP1001, was developed...
March 14, 2018: Lancet Haematology
Zhenquan Wang, Fengfeng Weng, Chen Li, Hongying Shi, Zhangke Tang, Huixian Qiu, Yue'e He, Rongzhou Wu, Maoping Chu
BACKGROUND: To evaluate differences in laboratory parameters, clinical presentation, and incidence of coronary artery lesions (CAL) between children with neutropenic and non-neutropenic Kawasaki disease (KD). METHODS: All consecutive KD patients that presented to the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University in Wenzhou, China between January 2005 and December 2015 were included in this study. Patients were divided into two groups (KD with neutropenia (NKD) and KD without neutropenia (NNKD)) based on whether or not they developed neutropenia during the course of treatment...
February 21, 2018: BMC Pediatrics
Xin-Ping Zhou, Xiu-Jin Ye, Jian-Ping Shen, Jian-Ping Lan, Hui-Fang Jiang, Jin Zhang, Xue-Jin Zhang, Li Li, Shen-Xian Qian, Hong-Yan Tong
The purpose of this prospective, multi-center study was to examine the efficacy and safety of tigecycline as empirical treatment in neutropenic patients with hematological malignancies who failed to respond to first-line antibiotics. A total of 125 patients with persistent fever (>72 h) despite first-line antibiotics received empirical treatment with tigecycline (loading dose of 100 mg, followed by 50 mg every 12 h). The use of other antimicrobial agents was not restricted. Treatment success rate was 68...
February 16, 2018: Leukemia & Lymphoma
Miao Zhao, Alexander J Lepak, Brian VanScoy, Justin C Bader, Karen Marchillo, Jamie Vanhecker, Paul G Ambrose, David R Andes
APX001 is the prodrug of APX001A, which is a first in class small molecule with a unique mechanism of action that inhibits the fungal enzyme (Gwt1) in the glycosylphosphatidylinositol (GPI) biosynthesis pathway. The goal of the present study was to determine which pharmacokinetic/pharmacodynamic (PK/PD) index and magnitude best correlated with efficacy in the murine disseminated candidiasis model for Candida albicans (n=5), C. glabrata (n=5) and C. auris (n=4). MIC values ranged from 0.002 to 0.03 mg/L for C...
January 29, 2018: Antimicrobial Agents and Chemotherapy
Stefano Ferrari, Stefan S Bielack, Sigbjørn Smeland, Alessandra Longhi, Gerlinde Egerer, Kirsten Sundby Hall, Davide Donati, Matthias Kevric, Otte Brosjö, Alessandro Comandone, Mathias Werner, Odd Monge, Emanuela Palmerini, Wolfgang E Berdel, Bodil Bjerkehagen, Anna Paioli, Sylvie Lorenzen, Mikael Eriksson, Marco Gambarotti, Per-Ulf Tunn, Nina L Jebsen, Marilena Cesari, Thekla von Kalle, Virginia Ferraresi, Rudolf Schwarz, Rossella Bertulli, Anne-Katrin Kasparek, Giovanni Grignani, Fatime Krasniqi, Benjamin Sorg, Stefanie Hecker-Nolting, Piero Picci, Peter Reichardt
INTRODUCTION: The EUROpean Bone Over 40 Sarcoma Study (EURO-B.O.S.S.) was the first prospective international study for patients 41-65 years old with high-grade bone sarcoma treated with an intensive chemotherapy regimen derived from protocols for younger patients with high-grade skeletal osteosarcoma. METHODS: Chemotherapy based on doxorubicin, cisplatin, ifosfamide, and methotrexate was suggested, but patients treated with other regimens at the investigators' choice were also eligible for the study...
December 5, 2017: Tumori
Alexander J Lepak, Miao Zhao, Brian VanScoy, Paul G Ambrose, David R Andes
Echinocandins are important in the prevention and treatment of invasive candidiasis but limited by current dosing regimens that include daily intravenous administration. The novel echinocandin CD101 has a prolonged half-life of approximately 130 h in humans, making it possible to design once-weekly dosing strategies. The present study examined the pharmacodynamic activity of CD101 using the neutropenic invasive candidiasis mouse model against select Candida albicans ( n = 4), C. glabrata ( n = 3), and C. parapsilosis ( n = 3) strains...
February 2018: Antimicrobial Agents and Chemotherapy
Thomas Neumann, Laila Schneidewind, Thomas Thiele, Daniel Pink, Meike Schulze, Christian Schmidt, William Krüger
BACKGROUND: Alemtuzumab as part of the conditioning protocol is effective in reducing graft-versus-host disease (GvHD), but may be associated with increased infection rates, especially when using high doses (ie, 100 mg). METHODS: We performed a retrospective, single-center, case-control study analyzing the rates of neutropenic fever, cytomegalovirus (CMV) reactivation, Epstein-Barr virus (EBV) reactivation, clinical manifest toxoplasmosis, and clinical manifest human herpesvirus-6 (HHV6) infection using low-dose alemtuzumab in comparison with anti-thymocyte globulin (ATG) as GvHD prophylaxis before allogeneic stem cell transplantation...
February 2018: Transplant Infectious Disease: An Official Journal of the Transplantation Society
Jennifer D Tieu, Sarah A Schmidt, Jamie L Miller, Katherine E Kupiec, Grant H Skrepnek, Connie Liu, Winter J Smith
Background Clostridium difficile infection treatment guidelines exist for immunocompetent patients; however, there is a paucity of data evaluating clinical outcomes and time to C. difficile-associated diarrhea resolution in neutropenic patients. Objective To assess clinical outcomes in neutropenic patients treated with metronidazole, oral vancomycin, the combination of metronidazole plus oral vancomycin, and switch of metronidazole to oral vancomycin. Methods This retrospective, observational cohort study assessed adult neutropenic inpatients with C...
January 1, 2017: Journal of Oncology Pharmacy Practice
Cornelia B Landersdorfer, Jiping Wang, Veronika Wirth, Ke Chen, Keith S Kaye, Brian T Tsuji, Jian Li, Roger L Nation
Background: The pharmacokinetic/pharmacodynamic (PK/PD) relationship for polymyxin B against Klebsiella pneumoniae infections is not known. Methods: Dose-fractionation studies with subcutaneous polymyxin B were conducted in neutropenic mice in which infection with three strains of K. pneumoniae had been produced in thighs or lungs. Dosing (thigh infection 0.5-120 mg/kg/day; lung infection 5-120 mg/kg/day) commenced 2 h after inoculation, and bacterial burden was measured 24 h later...
November 14, 2017: Journal of Antimicrobial Chemotherapy
Hideo Kato, Mao Hagihara, Eriko Murakami, Hiroyuki Suematsu, Naoya Nishiyama, Yusuke Koizumi, Yuka Yamagishi, Bunji Uno, Hiroshige Mikamo
Previous clinical studies have showed the clinical benefits of the initiation of treatment with a daptomycin (DAP) loading dose, but only a few studies have evaluated its antimicrobial benefits. We evaluated the efficacy of a DAP loading dose against methicillin-resistant Staphylococcus aureus (MRSA) infections in a neutropenic murine thigh infection model. Three MRSA isolates (DAP MIC: 0.5, 1, and 2 mg/L) were tested. Four DAP regimens simulating human concentration-time profiles, i.e., (i) day 1: 8 mg/kg and day 2: 6 mg/kg, (ii) days 1 and 2: 6 mg/kg/day, (iii) day 1: 8 mg/kg and day 2: 4 mg/kg, and (iv) days 1 and 2: 4 mg/kg/day, were administered to the mice...
November 11, 2017: Chemotherapy
Mojgan Sabet, Ziad Tarazi, Thomas Nolan, Jonathan Parkinson, Debora Rubio-Aparicio, Olga Lomovskaya, Michael N Dudley, David C Griffith
Meropenem-vaborbactam (Vabomere) is highly active against Gram-negative pathogens, especially Klebsiella pneumoniae carbapenemase (KPC)-producing, carbapenem-resistant Enterobacteriaceae The objective of these studies was to evaluate the efficacy of meropenem alone and in combination with vaborbactam in mouse thigh and lung infection models. Thighs or lungs of neutropenic mice were infected with KPC-producing carbapenem-resistant Enterobacteriaceae , with meropenem MICs ranging from ≤0.06 to 8 mg/liter in the presence of 8 mg/liter vaborbactam...
January 2018: Antimicrobial Agents and Chemotherapy
Aurelio B Castrellon, Michel Velez, Steven M Nguyen, Marcelo Blaya, Sandra Barnick, Katerine Dumais, Nicholas LeCroy, Luis E Raez
OBJECTIVE: To evaluate the effectiveness and tolerability of neoadjuvant chemotherapy with weekly paclitaxel in combination with weekly carboplatin area under curve 2 followed by anthracycline chemotherapy. PATIENTS AND METHODS: This is a retrospective review of electronic medical records of patients (N = 32) with stage 1c-III triple-negative breast cancer. Patients received neoadjuvant chemotherapy with paclitaxel 80 mg/m2 once per week for 12 weeks in combination with carboplatin area under curve 2 once per week for 12 weeks (wP + wCb), followed by a standard anthracycline regimen including either doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 every 2 or 3 weeks, or epirubicin 90 mg/m2 and cyclophosphamide 600 mg/m2 every 3 weeks for four cycles with myeloid growth factor support...
October 28, 2017: Hematology/oncology and Stem Cell Therapy
Asif Husain Osmani, Adnan Abdul Jabbar, Manesh Kumar Gangwani, Bilal Hassan
Fever during chemotherapy-induced neutropenia continues to be a major cause of morbidity and mortality in cancer patients. Mortality depends on the duration and degree of neutropenia, bacteremia, sepsis, performance status, comorbidities and other parameters. The highest mortality rates in cancer patients hospitalized with febrile neutropenia (FN) are observed in those with documented infection. The objectives of the study were to present available tools for risk assessment, to review pathogens causing infections in adult FN patients and to assess outcomes...
October 26, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
Lindsay A Hazelden, Matthew J Newman, Stephanie Shuey, Julie M Waldfogel, Victoria T Brown
Purpose Patients with head and neck cancer are at risk for disease- and treatment-related toxicities that may be severe enough to require hospitalization. The risk factors associated with hospitalization in these patients are not well defined. Methods We conducted a single-center, retrospective observational study of patients with head and neck cancer receiving chemotherapy at an academic medical center infusion clinic in a one-year period. The primary objective was to characterize the head and neck cancer population at an academic medical center...
January 1, 2017: Journal of Oncology Pharmacy Practice
Yu-Feng Zhou, Meng-Ting Tao, Yu-Zhang He, Jian Sun, Ya-Hong Liu, Xiao-Ping Liao
Antimicrobial resistance among uropathogens has increased infection-related morbidity and mortality. Antofloxacin is a novel fluoroquinolone with broad-spectrum antibacterial activity against urinary Gram-negative bacilli such as Escherichia coli This study monitored the in vivo efficacy of antofloxacin using bioluminescence imaging and determined pharmacokinetic/pharmacodynamic (PK/PD) targets against E. coli isolates in a neutropenic murine thigh infection model. The PK properties were performed after subcutaneous antofloxacin administration of 2...
October 16, 2017: Antimicrobial Agents and Chemotherapy
Anthony Oyekunle, Evgenii Shumilov, Philippe Kostrewa, Andreas Burchert, Lorenz Trümper, Patrick Wuchter, Gerald Wulf, Ulrike Bacher, Nicolaus Kröger
Novel induction agents markedly improved remission rates in multiple myeloma (MM), and the continued use of chemotherapy for CD34+ stem cell mobilization (SCM) has been questioned. We examined the additional effect of chemotherapy in SCM regarding remission status/morbidity. We reviewed 236 consecutive MM patients (aged 36 to 75 years) with first autologous stem cell transplantation from January 2009 to March 2016 after chemotherapy-based SCM. Responses were measured by changes in intact Ig and free light chain levels before and after chemomobilization (International Myeloma Working Group [IMWG] criteria)...
February 2018: Biology of Blood and Marrow Transplantation
Rajbharan Yadav, Jürgen B Bulitta, Jiping Wang, Roger L Nation, Cornelia B Landersdorfer
We previously optimized imipenem and tobramycin combination regimens against a double-resistant clinical Pseudomonas aeruginosa isolate by using in vitro infection models, mechanism-based pharmacokinetic/pharmacodynamic modeling (MBM), and Monte Carlo simulations. The current study aimed to evaluate these regimens in a neutropenic murine thigh infection model and to characterize the time course of bacterial killing and regrowth via MBM. We studied monotherapies and combinations of imipenem with tobramycin in vivo against the double-resistant clinical P...
December 2017: Antimicrobial Agents and Chemotherapy
V Ramos-Martín, A Johnson, L McEntee, N Farrington, K Padmore, P Cojutti, F Pea, M N Neely, W W Hope
Objectives: The overall study aim was to identify the relevant preclinical teicoplanin pharmacokinetic (PK)/pharmacodynamic (PD) indices to predict efficacy and suppression of resistance in MRSA infection. Methods: A hollow-fibre infection model and a neutropenic murine thigh infection model were developed. The PK/PD data generated were modelled using a non-parametric population modelling approach with Pmetrics. The posterior Bayesian estimates derived were used to study the exposure-effect relationships...
December 1, 2017: Journal of Antimicrobial Chemotherapy
L A Dunn, M G Fury, H Xiao, S S Baxi, E J Sherman, S Korte, C Pfister, S Haque, N Katabi, A L Ho, D G Pfister
Background: Activating events along the PI3K/mTOR pathway are common in head and neck squamous cell carcinomas (HNSCC), and preclinical studies suggest additive or synergistic effects when combining mTORC1 inhibitors with carboplatin and paclitaxel chemotherapy. Patients and methods: In this single-institution phase II study, the combination of temsirolimus 25 mg, carboplatin AUC 1.5, and paclitaxel 80 mg/m2 administered on days 1 and 8 of a 21-day cycle was evaluated in 36 patients with recurrent and/or metastatic (R/M) HNSCC...
October 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Daniel P Petrylak, Ronald de Wit, Kim N Chi, Alexandra Drakaki, Cora N Sternberg, Hiroyuki Nishiyama, Daniel Castellano, Syed Hussain, Aude Fléchon, Aristotelis Bamias, Evan Y Yu, Michiel S van der Heijden, Nobuaki Matsubara, Boris Alekseev, Andrea Necchi, Lajos Géczi, Yen-Chuan Ou, Hasan Senol Coskun, Wen-Pin Su, Miriam Hegemann, Ivor J Percent, Jae-Lyun Lee, Marcello Tucci, Andrey Semenov, Fredrik Laestadius, Avivit Peer, Giampaolo Tortora, Sufia Safina, Xavier Garcia Del Muro, Alejo Rodriguez-Vida, Irfan Cicin, Hakan Harputluoglu, Ryan C Widau, Astra M Liepa, Richard A Walgren, Oday Hamid, Annamaria H Zimmermann, Katherine M Bell-McGuinn, Thomas Powles
BACKGROUND: Few treatments with a distinct mechanism of action are available for patients with platinum-refractory advanced or metastatic urothelial carcinoma. We assessed the efficacy and safety of treatment with docetaxel plus either ramucirumab-a human IgG1 VEGFR-2 antagonist-or placebo in this patient population. METHODS: We did a randomised, double-blind, phase 3 trial in patients with advanced or metastatic urothelial carcinoma who progressed during or after platinum-based chemotherapy...
September 12, 2017: Lancet
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