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https://www.readbyqxmd.com/read/28431010/clinical-trial-of-the-anti-pd-l1-antibody-bms-936559-in-hiv-1-infected-participants-on-suppressive-antiretroviral-therapy
#1
Cynthia L Gay, Ronald J Bosch, Justin Ritz, Jason M Hataye, Evgenia Aga, Randall L Tressler, Stephen W Mason, Carey K Hwang, Dennis M Grasela, Neelanjana Ray, Josh C Cyktor, John M Coffin, Edward P Acosta, Richard A Koup, John W Mellors, Joseph J Eron
Background.: Reversing immune exhaustion with an anti-PD-L1 antibody may improve HIV-1-specific immunity and increase clearance of HIV-1 expressing cells. Methods.: Phase I, randomized, double-blind, placebo-controlled dose-escalating study of BMS-936559including HIV-1-infected adults ≥18 to ≤70 years on suppressive antiretroviral therapy with CD4+ counts ≥350 cells/μL and detectable plasma HIV-1 RNA by single copy assay. Data on single infusions of BMS-936559 (0...
April 18, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28430648/radioimmunotherapy-for-cd133-colonic-cancer-stem-cells-inhibits-tumor-development-in-nude-mice
#2
Dinghu Weng, Xueyan Jin, Saimei Qin, Xiaoli Lan, Chong Chen, Xun Sun, Xianliang She, Changling Dong, Rui An
Accumulating evidence indicates that cancer stem cells (CSCs) are the cause of tumor drug/radio-resistance or distant metastasis; therefore, it is essential to eliminate CSCs to cure cancer completely. The purpose of this study was to utilize radioimmunotherapy (RIT) to target CD133(+) colonic CSCs and observe whether this prevented tumor development, by assessing the maximum tolerated dose (MTD) of HCT116 tumor-bearing nude mice with escalating doses of 131I-AC133.1 monoclonal antibody (mAb), and determining the therapeutic efficacy of RIT with 131I-AC133...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28429140/a-phase-i-ii-study-on-stereotactic-body-radiotherapy-with-real-time-tumor-tracking-using-cyberknife-based-on-the-monte-carlo-algorithm-for-lung-tumors
#3
Hiromitsu Iwata, Satoshi Ishikura, Taro Murai, Michio Iwabuchi, Mitsuhiro Inoue, Koshi Tatewaki, Seiji Ohta, Naoki Yokota, Yuta Shibamoto
BACKGROUND: In this phase I/II study, we assessed the safety and initial efficacy of stereotactic body radiotherapy (SBRT) for lung tumors with real-time tumor tracking using CyberKnife based on the Monte Carlo algorithm. METHODS: Study subjects had histologically confirmed primary non-small-cell lung cancer staged as T1a-T2aN0M0 and pulmonary oligometastasis. The primary endpoint was the incidence of Grade ≥3 radiation pneumonitis (RP) within 180 days of the start of SBRT...
April 20, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28428884/phase-i-clinical-trial-of-combination-imatinib-and-ipilimumab-in-patients-with-advanced-malignancies
#4
Matthew J Reilley, Ann Bailey, Vivek Subbiah, Filip Janku, Aung Naing, Gerald Falchook, Daniel Karp, Sarina Piha-Paul, Apostolia Tsimberidou, Siqing Fu, JoAnn Lim, Stacie Bean, Allison Bass, Sandra Montez, Luis Vence, Padmanee Sharma, James Allison, Funda Meric-Bernstam, David S Hong
BACKGROUND: Imatinib mesylate can induce rapid tumor regression, increase tumor antigen presentation, and inhibit tumor immunosuppressive mechanisms. CTLA-4 blockade and imatinib synergize in mouse models to reduce tumor volume via intratumoral accumulation of CD8+ T cells. We hypothesized that imatinib combined with ipilimumab would be tolerable and may synergize in patients with advanced cancer. METHODS: Primary objective of the dose-escalation study (3 + 3 design) was to establish the maximum tolerated dose (MTD) and recommended phase II dose...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28427525/precision-medicine-for-early-breast-cancer-radiotherapy-opening-up-new-horizons
#5
REVIEW
Jacques Bernier
So far most efforts put forth to test the value of predictive and prognostic tools in the field of breast radiotherapy remained globally disappointing, or at least below the convincing levels reached for systemic therapy. Nevertheless the addition of predictive tools to the clinical armament tends to prevail over the use of the sole prognostic factors, also in radiotherapy. A number of predictive assays, clinically validated or not, have recently elicited significant associations between molecular profiles and tumor biological aggressiveness and/or radiosensitivity levels...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28427153/comparison-between-proton-boron-fusion-therapy-pbft-and-boron-neutron-capture-therapy-bnct-a-monte-carlo-study
#6
Joo-Young Jung, Do-Kun Yoon, Brendan Barraclough, Heui Chang Lee, Tae Suk Suh, Bo Lu
The aim of this study is to compare between proton boron fusion therapy (PBFT) and boron neutron capture therapy (BNCT) and to analyze dose escalation using a Monte Carlo simulation. We simulated a proton beam passing through the water with a boron uptake region (BUR) in MCNPX. To estimate the interaction between neutrons/protons and borons by the alpha particle, the simulation yielded with a variation of the center of the BUR location and proton energies. The variation and influence about the alpha particle were observed from the percent depth dose (PDD) and cross-plane dose profile of both the neutron and proton beams...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28426845/her2-specific-chimeric-antigen-receptor-modified-virus-specific-t-cells-for-progressive-glioblastoma-a-phase-1-dose-escalation-trial
#7
Nabil Ahmed, Vita Brawley, Meenakshi Hegde, Kevin Bielamowicz, Mamta Kalra, Daniel Landi, Catherine Robertson, Tara L Gray, Oumar Diouf, Amanda Wakefield, Alexia Ghazi, Claudia Gerken, Zhongzhen Yi, Aidin Ashoori, Meng-Fen Wu, Hao Liu, Cliona Rooney, Gianpietro Dotti, Adrian Gee, Jack Su, Yvonne Kew, David Baskin, Yi Jonathan Zhang, Pamela New, Bambi Grilley, Milica Stojakovic, John Hicks, Suzanne Z Powell, Malcolm K Brenner, Helen E Heslop, Robert Grossman, Winfried S Wels, Stephen Gottschalk
Importance: Glioblastoma is an incurable tumor, and the therapeutic options for patients are limited. Objective: To determine whether the systemic administration of HER2-specific chimeric antigen receptor (CAR)-modified virus-specific T cells (VSTs) is safe and whether these cells have antiglioblastoma activity. Design, Setting, and Participants: In this open-label phase 1 dose-escalation study conducted at Baylor College of Medicine, Houston Methodist Hospital, and Texas Children's Hospital, patients with progressive HER2-positive glioblastoma were enrolled between July 25, 2011, and April 21, 2014...
April 20, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28426675/indicators-of-suboptimal-biologic-therapy-over-time-in-patients-with-ulcerative-colitis-and-crohn-s-disease-in-the-united-states
#8
Haridarshan Patel, Trevor Lissoos, David T Rubin
This study assessed the occurrence of indicators for suboptimal biologic therapy among ulcerative colitis (UC) and Crohn's disease (CD) patients over time in the United States (US). Data from a large US claims database (2005-2013) were used to retrospectively identify patients with diagnosed with either UC or CD who were new biologic users. Indicators of suboptimal biologic therapy included: dose escalation during the maintenance phase, discontinuation of the initial biologic, switch to another biologic within 90 days following the last day of supply of the initial biologic, augmentation with a non-biologic systemic therapy, UC- or CD-related surgery, UC- or CD-related urgent care, and development of fistula (for CD only)...
2017: PloS One
https://www.readbyqxmd.com/read/28426137/hydroxyurea-hydroxycarbamide-for-sickle-cell-disease
#9
REVIEW
Sarah J Nevitt, Ashley P Jones, Jo Howard
BACKGROUND: Sickle cell disease (SCD) is one of the most common inherited diseases worldwide. It is associated with lifelong morbidity and a reduced life expectancy. Hydroxyurea (hydroxycarbamide), an oral chemotherapeutic drug, ameliorates some of the clinical problems of SCD, in particular that of pain, by raising fetal haemoglobin. This is an update of a previously published Cochrane Review. OBJECTIVES: To assess the effects of hydroxyurea therapy in people with SCD (all genotypes), of any age, regardless of setting...
April 20, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28424963/pharmacokinetics-and-safety-of-carfilzomib-in-patients-with-relapsed-multiple-myeloma-and-end-stage-renal-disease-esrd-an-open-label-single-arm-phase-i-study
#10
Hang Quach, Darrell White, Andrew Spencer, P Joy Ho, Divaya Bhutani, Mike White, Sandeep Inamdar, Chris Morris, Ying Ou, Martin Gyger
PURPOSE: The pharmacokinetics (PK) of carfilzomib have been previously studied in multiple myeloma patients with varying degrees of renal impairment (normal, mild, moderate, severe, and end-stage renal disease [ESRD]) at doses of 15 and 20 mg/m(2). This study evaluated carfilzomib PK at higher doses of 27 and 56 mg/m(2) in normal renal function and ESRD patients. METHODS: Patients received carfilzomib on two consecutive days/week for 3 weeks every 28-day cycle: 20 mg/m(2) (cycle 1 day 1-2), escalated to 27 mg/m(2) on cycle 1 day 8; if tolerated, 56 mg/m(2) starting cycle 2 day 1...
April 19, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28424962/phase-i-dose-escalation-study-of-milciclib-in-combination-with-gemcitabine-in-patients-with-refractory-solid-tumors
#11
Sandrine Aspeslagh, Kunwar Shailubhai, Rastilav Bahleda, Anas Gazzah, Andréa Varga, Antoine Hollebecque, Christophe Massard, Anna Spreafico, Michele Reni, Jean-Charles Soria
BACKGROUND: This phase I trial evaluated the safety and tolerability of milciclib, an inhibitor of multiple cyclin-dependent kinases and tropomycin receptor kinase A, in combination with gemcitabine in patients with refractory solid tumors. DESIGN: Sixteen patients were enrolled and treated with milciclib at three dose levels (45 mg/m(2)/day, n = 3; 60 mg/m(2)/day, n = 3; and 80 mg/m(2)/day, n = 10) with a fixed dose of gemcitabine (1000 mg/m(2)/day). Milciclib was administered orally once daily for 7 days on/7 days off in a 4-week cycle, and gemcitabine was administered intravenously on days 1, 8 and 15 in a 4-week cycle...
April 19, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28424891/a-phase-i-dose-escalation-study-of-selumetinib-in-combination-with-erlotinib-or-temsirolimus-in-patients-with-advanced-solid-tumors
#12
Jeffrey R Infante, Roger B Cohen, Kevin B Kim, Howard A Burris, Gregory Curt, Ugochi Emeribe, Delyth Clemett, Helen K Tomkinson, Patricia M LoRusso
Background Combinations of molecularly targeted agents may provide optimal anti-tumor activity and improve clinical outcomes for patients with advanced cancers. Selumetinib (AZD6244, ARRY-142886) is an oral, potent and highly selective, allosteric inhibitor of MEK1/2, a component of the RAS/RAF/MEK/ERK pathway which is constitutively activated in many cancers. We investigated the safety, tolerability, and pharmacokinetics (PK) of selumetinib in combination with molecularly targeted drugs erlotinib or temsirolimus in patients with advanced solid tumors...
April 19, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28424876/extent-of-surgical-resection-and-adjuvant-temozolomide-improves-survival-in-pediatric-gbm-a-single-center-experience
#13
Subhash Gupta, Supriya Mallick, Rony Benson, K P Haresh, Pramod Kumar Julka, Goura Kishor Rath
BACKGROUND: Pediatric glioblastoma (pGBM) is an uncommon entity. The importance of concurrent and adjuvant temozolomide is not known in this subset of patients. METHODS: We retrospectively analyzed our database between 2000 and 2015. All patients were treated with maximally safe surgical resection. This was followed by a uniform treatment schedule of post-operative radiation with concurrent daily temozolomide at 75 mg/m(2). Radiation dose was 60 Gy in 30 fractions planned by 3-dimensional conformal radiotherapy...
April 19, 2017: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/28423367/imatinib-dose-escalation-versus-sunitinib-as-a-second-line-treatment-against-advanced-gastrointestinal-stromal-tumors-a-nationwide-population-based-cohort-study
#14
Jun-Te Hsu, Puo-Hsien Le, Chang-Fu Kuo, Meng-Jiun Chiou, Chia-Jung Kuo, Tsung-Hsing Chen, Chun-Jung Lin, Jen-Shi Chen, Huang-Pin Yu, Chun-Nan Yeh, Yi-Yin Jan, Ta-Sen Yeh
BACKGROUND: Although treatment with imatinib in advanced gastrointestinal stromal tumor (GIST) patients has led to significant clinical benefits, the disease will eventually progress due to imatinib resistance. Treatment options after failure of first-line imatinib include imatinib dose escalation or shifting to sunitinib. However, there is no large-scale study to compare the efficacy difference between these two treatment strategies or the role of surgery. RESULTS: This study recruited 521 advanced GIST patients including 246, 125, and 150 placed in groups 1, 2, and 3, respectively...
April 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421991/patterns-in-use-and-costs-of-conventional-and-biologic-disease-modifying-anti-rheumatic-drugs-in-australia
#15
Ellen Donges, Christine Staatz, Helen Benham, Paul Kubler, Samantha A Hollingworth
OBJECTIVES: The aim of this study was to characterise the use and costs of subsidising conventional disease-modifying anti-rheumatic drugs (DMARDs) and biologic DMARDs in Australia from 2004-2014 through pharmaceutical benefits schemes. METHODS: Dispensing and expenditure data on conventional and biologic DMARDs were extracted from Medicare Australia and temporal trends were analysed. Medicine use was standardised in terms of the defined daily dose (DDD) per 1,000 population per day (DDD/1,000 population/day)...
April 18, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28421383/pharmacokinetics-safety-and-tolerability-of-single-and-multiple-doses-of-guanfacine-extended-release-formulation-in-healthy-japanese-and-caucasian-male-adults
#16
Yumiko Matsuo, Masafumi Okita, James Ermer, Toshihiro Wajima
BACKGROUND AND OBJECTIVE: Guanfacine extended-release (guanfacine XR) could be a useful treatment option for children and adolescent patients with attention-deficit/hyperactivity disorder (ADHD). As an initial step in the development in Japan, the pharmacokinetics, safety and tolerability were assessed in healthy Japanese and non-Hispanic Caucasian adults. METHODS: A Phase 1, double-blind, randomized, placebo-controlled, single- and multiple-oral dose escalation study of guanfacine XR was conducted...
April 18, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/28421162/r-ideal-a-framework-for-systematic-clinical-evaluation-of-technical-innovations-in-radiation-oncology
#17
Helena M Verkooijen, Linda G W Kerkmeijer, Clifton D Fuller, Robbert Huddart, Corinne Faivre-Finn, Marcel Verheij, Stella Mook, Arjun Sahgal, Emma Hall, Chris Schultz
The pace of innovation in radiation oncology is high and the window of opportunity for evaluation narrow. Financial incentives, industry pressure, and patients' demand for high-tech treatments have led to widespread implementation of innovations before, or even without, robust evidence of improved outcomes has been generated. The standard phase I-IV framework for drug evaluation is not the most efficient and desirable framework for assessment of technological innovations. In order to provide a standard assessment methodology for clinical evaluation of innovations in radiotherapy, we adapted the surgical IDEAL framework to fit the radiation oncology setting...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28420720/a-phase-i-study-of-abc294640-a-first-in-class-sphingosine-kinase-2-inhibitor-in-patients-with-advanced-solid-tumors
#18
Carolyn D Britten, Melanie B Thomas, Elizabeth Garrett-Mayer, Steven H Chin, Keisuke Shirai, Besim Ogretmen, Tricia A Bentz, Alan Brisendine, Kate Anderton, Susan L Cusack, Lynn W Maines, Yan Zhuang, Charles D Smith
Purpose:  Sphingosine kinases (SK1 and SK2) regulate tumor growth by generating the mitogenic and pro-inflammatory lipid sphingosine 1-phosphate (S1P). This phase I study investigated the safety, pharmacokinetics, pharmacodynamics and anti-tumor activity of ABC294640, a first-in-class orally-available inhibitor of SK2.  <p>Experimental Design:  Escalating doses of ABC294640 were administered orally to patients with advanced solid tumors in sequential cohorts at the following dose levels: 250 mg qd, 250 mg bid, 500 mg bid and 750 mg bid, continuously in cycles of 28 days...
April 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28418614/efficacy-and-safety-of-low-dose-heparin-in-hemodialysis
#19
Mariana Murea, Gregory B Russell, Pirouz Daeihagh, Anita M Saran, Karan Pandya, Mark Cabrera, John M Burkart, Barry I Freedman
INTRODUCTION: The dose of unfractionated heparin (UFH) administered during hemodialysis (HD) varies widely. This prospective study evaluated the safety and efficacy of UFH dose de-escalation. METHODS: Sixty-six prevalent patients on HD receiving UFH per standard-dose protocol (load dose [LD] 50-75 units/kg, maintenance dose [MD] 500-1000 units/hour) had heparin prescription converted to low-dose protocol (start LD 15 units/kg and MD 500 units/hour; dose adjusted in small increments based on assessments of extracorporeal blood circuit)...
April 18, 2017: Hemodialysis International
https://www.readbyqxmd.com/read/28417284/a-phase-i-dose-escalation-study-of-the-safety-and-pharmacokinetics-of-a-tablet-formulation-of-voxtalisib-a-phosphoinositide-3-kinase-inhibitor-in-patients-with-solid-tumors
#20
Janice M Mehnert, Gerald Edelman, Mark Stein, Heather Camisa, Joanne Lager, Jean-François Dedieu, Anne-Frédérique Ghuysen, Jyoti Sharma, Li Liu, Patricia M LoRusso
Background Voxtalisib, a PI3K/mTOR inhibitor, has shown antitumor activity in capsule formulation in patients with solid tumors. This Phase I study assessed safety and pharmacokinetics of voxtalisib administered as immediate-release tablets in patients with solid tumors (NCT01596270). Methods A "3 + 3" dose escalation design was used. Adverse events (AEs), pharmacokinetics (PK), food effect and tumor response were evaluated. Results Thirty-two patients received voxtalisib doses ranging from 50 mg to 70 mg once daily (QD) and 17 patients received voxtalisib doses ranging from 30 mg to 50 mg twice daily (BID), for two 28-day cycles...
April 17, 2017: Investigational New Drugs
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