keyword
MENU ▼
Read by QxMD icon Read
search

Dose escalation

keyword
https://www.readbyqxmd.com/read/28636538/phase-i-dose-escalation-study-of-the-c-met-tyrosine-kinase-inhibitor-sar125844-in-asian-patients-with-advanced-solid-tumors-including-patients-with-met-amplified-gastric-cancer
#1
Kohei Shitara, Tae Min Kim, Tomoya Yokota, Masahiro Goto, Taroh Satoh, Jin-Hee Ahn, Hyo Song Kim, Sylvie Assadourian, Corinne Gomez, Marzia Harnois, Satoshi Hamauchi, Toshihiro Kudo, Toshihido Doi, Yung-Jue Bang
SAR125844 is a potent and selective inhibitor of the c-Met kinase receptor. This was an open-label, phase I, multicenter, dose-escalation, and dose-expansion trial of SAR125844 in Asian patients with solid tumors, a subgroup of whom had gastric cancer and MET amplification (NCT01657214). SAR125844 was administered by intravenous infusion (260-570 mg/m2) on days 1, 8, 15, and 22 of each 28-day cycle. Objectives were to determine the maximum tolerated dose (MTD) and to evaluate SAR125844 safety and pharmacokinetic profile...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28634283/phase-ib-study-of-utomilumab-pf-05082566-a-4-1bb-cd137-agonist-in-combination-with-pembrolizumab-mk-3475-in-patients-with-advanced-solid-tumors
#2
Anthony W Tolcher, Mario Sznol, Siwen Hu-Lieskovan, Kyriakos P Papadopoulos, Amita Patnaik, Drew Rasco, Donna Di Gravio, Bo Huang, Dhiraj Gambhire, Ying Chen, Aron Thall, Nuzhat Pathan, Emmett V Schmidt, Laura Q M Chow
Purpose:  This phase Ib study (NCT02179918) evaluated the safety, antitumor activity, pharmacokinetics, and pharmacodynamics of utomilumab, a fully human IgG2 mAb agonist of the T-cell costimulatory receptor 4-1BB/CD137 in combination with the humanized, PD-1-blocking IgG4 mAb pembrolizumab in patients with advanced solid tumors. <p>Experimental Design:  Utomilumab (0.45-5.0 mg/kg) and pembrolizumab (2 mg/kg) were administered intravenously every 3 weeks. Utomilumab dose escalation was conducted using the time-to-event-continual reassessment method...
June 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28632196/drug-hypersensitivity-and-desensitizations-mechanisms-and-new-approaches
#3
REVIEW
Leticia de Las Vecillas Sánchez, Leila A Alenazy, Marlene Garcia-Neuer, Mariana C Castells
Drug hypersensitivity reactions (HSRs) are increasing in the 21st Century with the ever expanding availability of new therapeutic agents. Patients with cancer, chronic inflammatory diseases, cystic fibrosis, or diabetes can become allergic to their first line therapy after repeated exposures or through cross reactivity with environmental allergens. Avoidance of the offending allergenic drug may impact disease management, quality of life, and life expectancy. Precision medicine provides new tools for the understanding and management of hypersensitivity reactions (HSRs), as well as a personalized treatment approach for IgE (Immunoglobuline E) and non-IgE mediated HSRs with drug desensitization (DS)...
June 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28631197/prioritizing-future-research-on-allopurinol-and-febuxostat-for-the-management-of-gout-value-of-information-analysis
#4
Eric Jutkowitz, Fernando Alarid-Escudero, Hyon K Choi, Karen M Kuntz, Hawre Jalal
OBJECTIVES: The aim of this study was to quantify the value of conducting additional research and reducing uncertainty regarding the cost effectiveness of allopurinol and febuxostat for the management of gout. METHODS: We used a previously developed Markov model that evaluated the cost effectiveness of nine urate-lowering strategies: no treatment, allopurinol-only fixed dose (300 mg), allopurinol-only dose escalation (up to 800 mg), febuxostat-only fixed dose (80 mg), febuxostat-only dose escalation (up to 120 mg), allopurinol-febuxostat sequential therapy fixed dose, allopurinol-febuxostat sequential therapy dose escalation, febuxostat-allopurinol sequential therapy fixed dose, and febuxostat-allopurinol sequential therapy dose escalation...
June 19, 2017: PharmacoEconomics
https://www.readbyqxmd.com/read/28630876/a-dosimetric-comparison-of-dose-escalation-with-simultaneous-integrated-boost-for-locally-advanced-non-small-cell-lung-cancer
#5
Wenjuan Yang, Biao Zeng, Yanfang Qiu, Jianfeng Tan, Shilei Xu, Yilong Cai, Yujuan Zhou, Zhigang Liu, Junming Luo, Hui Wang
BACKGROUND: Many studies have demonstrated that a higher radiotherapy dose is associated with improved outcomes in non-small-cell lung cancer (NSCLC). We performed a dosimetric planning study to assess the dosimetric feasibility of intensity-modulated radiation therapy (IMRT) with a simultaneous integrated boost (SIB) in locally advanced NSCLC. METHODS: We enrolled twenty patients. Five different dose plans were generated for each patient. All plans were prescribed a dose of 60 Gy to the planning tumor volume (PTV)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28629442/treatment-patterns-healthcare-resource-utilization-and-costs-following-first-line-antidepressant-treatment-in-major-depressive-disorder-a-retrospective-us-claims-database-analysis
#6
Geneviève Gauthier, Annie Guérin, Maryia Zhdanava, William Jacobson, George Nomikos, Elizabeth Merikle, Clément François, Vanessa Perez
BACKGROUND: Although the symptoms of major depressive disorder (MDD) are often manageable with pharmacotherapy, response to first-line antidepressant treatment is often less than optimal. This study describes long-term treatment patterns in MDD patients in the United States and quantifies the economic burden associated with different treatment patterns following first-line antidepressant therapy. METHODS: MDD patients starting first-line antidepressant monotherapy and having continuous enrollment ≥12 months before and ≥24 months following the index date (i...
June 19, 2017: BMC Psychiatry
https://www.readbyqxmd.com/read/28628679/safety-and-efficacy-of-escalating-doses-of-ingenol-mebutate-for-field-treatment-of-actinic-keratosis-on-the-full-face-full-balding-scalp-or-chest
#7
C William Hanke, Brian Berman, Neil Swanson, David M Pariser, Jonathan S Weiss, Michael Bukhalo, Torsten Skov, John Villumsen, Daniel Siegel
<p>Background: Actinic keratosis (AK) can affect large skin areas. Ingenol mebutate (IngMeb) gel (0.015% and 0.05%) is approved for topical treatment of AK in a single contiguous area of ~25 cm2.</p> <p>Objective: The study sought to determine the maximum tolerated dose (MTD), efficacy, and tolerability of IngMeb applied to AK on a contiguous area less than equal to 250 cm2.</p> <p>Methods: Part 1 determined the MTD of IngMeb at 7 concentrations for 2 or 3 days. Part 2 assessed efficacy and tolerability at the MTD and one dose lower for 2 or 3 days vs vehicle...
May 1, 2017: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/28627952/clinical-efficacy-of-piperacillin-tazobactam-in-the-treatment-of-complicated-skin-and-soft-tissue-infections
#8
Kohei Takimoto, Qianzhi Wang, Daisuke Suzuki, Mitsuya Katayama, Yoshiro Hayashi
Introduction Complicated skin and soft tissue infections (cSSTIs) are skin and soft tissue infections (SSTIs) that involve deep soft tissue. cSSTIs often require surgical intervention and/or hospitalization. cSSTIs are associated with significant mortality and morbidity, and carry a significant burden on health care systems. Piperacillin/tazobactam has been regarded as a standard treatment for cSSTIs because of its antibiotic spectrum, safety and clinical efficacy. Several antibiotics, as compared to piperacillin/tazobactam, have been evaluated in the treatment of cSSTIs...
June 19, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28624695/first-in-human-phase-i-study-of-oral-s49076-a-unique-met-axl-fgfr-inhibitor-in-advanced-solid-tumours
#9
Jordi Rodon, Sophie Postel-Vinay, Antoine Hollebecque, Paolo Nuciforo, Analia Azaro, Valérie Cattan, Lucie Marfai, Isabelle Sudey, Karl Brendel, Audrey Delmas, Stéphanie Malasse, Jean-Charles Soria
BACKGROUND AND OBJECTIVES: S49076 is a novel ATP-competitive tyrosine kinase inhibitor of MET, AXL and FGFR with a unique selectivity profile. A phase I open-label study was undertaken to establish the tolerability profile and determine the recommended dose (RD) and administration schedule. MATERIALS AND METHODS: Patients with advanced solid tumours received S49076 orally once-daily (qd) or twice-daily (bid) in continuous 21-day cycles at escalating doses guided by a 3 + 3 design and followed by an expansion phase at the RD...
June 15, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28623085/variability-of-treatment-planning-of-seed-implantation-a-japanese-multicenter-simulation-study
#10
Hiromichi Ishiyama, Masahiro Nakano, Kazuhito Toya, Ryuichi Kota, Koyo Kikuchi, Takahiro Yamaguchi, Naoaki Kono, Shogo Kawakami, Yuki Tsutsumi, Tomoki Tanaka, Takahisa Eriguchi, Saiji Ohga, Toshihiro Yamaguchi, Yoshiaki Takakawa, Masashi Morita, Norihisa Katayama, Toshio Ohashi, Manabu Aoki, Atsunori Yorozu, Siro Saito
PURPOSE: This multicenter study was conducted to evaluate the current variability of treatment planning of seed implantation in Japanese centers and the feasibility of two virtual trials. METHODS AND MATERIALS: Two types of contour data were sent to 12 radiation oncologists with a request letter that asked them to make treatment plans on the data in the same manner as in their own practice. Five of the 12 radiation oncologists were asked to participate in the two virtual trials in which the D90 (dose to the hottest 90% of prostate volume) was 1) required to be set at just 180 Gy and 2) increased as much as possible without violating other limitations...
June 13, 2017: Brachytherapy
https://www.readbyqxmd.com/read/28622959/a-phase-i-ii-trial-of-panobinostat-in-combination-with-lenalidomide-in-patients-with-relapsed-or-refractory-hodgkin-lymphoma
#11
Joseph J Maly, Beth A Christian, Xiaohua Zhu, Lai Wei, Jennifer L Sexton, Samantha M Jaglowski, Steven M Devine, Todd A Fehniger, Nina D Wagner-Johnston, Mitch A Phelps, Nancy L Bartlett, Kristie A Blum
BACKGROUND: Lenalidomide and panobinostat have shown single-agent efficacy of 14% to 50% and 27% to 58%, respectively, in Hodgkin lymphoma (HL). This phase I/II study was conducted to determine the maximum tolerated dose (MTD), safety, and efficacy of lenalidomide combined with panobinostat in relapsed/refractory HL. PATIENTS AND METHODS: In the phase I trial, previously treated patients with classical or lymphocyte-predominant HL received escalating doses of lenalidomide on days 1 to 21 and panobinostat 3 times a week (TIW) every 28 days...
June 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28622210/serotonin-syndrome-following-combined-administration-of-dopaminergic-and-noradrenergic-agents-in-a-patient-with-akinetic-mutism-after-frontal-intracerebral-hemorrhage-a-case-report
#12
Dae Geun Jeon, Yong Wook Kim, Na Young Kim, Jung Hyun Park
BACKGROUND: Serotonin syndrome (SS) is a potentially life-threatening condition that can be caused by use of proserotonergic drugs. Several studies have reported that combined administration of various medications may induce SS. We report a case of SS in a patient who was being treated with dopaminergic and noradrenergic drugs. CASE PRESENTATION: A 55-year-old man with a right frontal intracerebral hemorrhage extending to the left cerebral hemisphere presented with clinical features of akinetic mutism...
June 16, 2017: Clinical Neuropharmacology
https://www.readbyqxmd.com/read/28620942/a-dose-escalation-study-of-combretastatin-a4-phosphate-in-healthy-dogs
#13
E Abma, P Smets, S Daminet, I Cornelis, K De Clercq, Y Ni, L Vlerick, H de Rooster
Combretastatin A4-Phosphate (CA4P) is a vascular disrupting agent revealing promising results in cancer treatments for humans. The aim of this study was to investigate the safety and adverse events of CA4P in healthy dogs as a prerequisite to application of CA4P in dogs with cancer. Ten healthy dogs were included. The effects of escalating doses of CA4P on physical, haematological and biochemical parameters, systolic arterial blood pressure, electrocardiogram, echocardiographic variables and general wellbeing were characterised...
June 16, 2017: Veterinary and Comparative Oncology
https://www.readbyqxmd.com/read/28619227/efficacy-and-safety-of-praziquantel-in-preschool-aged-and-school-aged-children-infected-with-schistosoma-mansoni-a-randomised-controlled-parallel-group-dose-ranging-phase-2-trial
#14
Jean T Coulibaly, Gordana Panic, Kigbafori D Silué, Jana Kovač, Jan Hattendorf, Jennifer Keiser
BACKGROUND: Praziquantel has been the drug of choice for schistosomiasis control for more than 40 years, yet surprisingly, the optimal dose for children younger than 4 years is not known. We aimed to assess the efficacy and safety of escalating praziquantel dosages in preschool-aged children (PSAC). METHODS: We did a randomised controlled, parallel-group, single-blind, dose-ranging, phase 2 trial in PSAC (2-5 years) and school-aged children (SAC; aged 6-15 years) as a comparator group in southern Côte d'Ivoire...
July 2017: Lancet Global Health
https://www.readbyqxmd.com/read/28618305/phase-i-study-of-temsirolimus-in-combination-with-cetuximab-in-patients-with-advanced-solid-tumours
#15
A Hollebecque, R Bahleda, L Faivre, J Adam, V Poinsignon, A Paci, C Gomez-Roca, J C Thery, M C Le Deley, A Varga, A Gazzah, E Ileana, M Gharib, E Angevin, K Malekzadeh, C Massard, J C Soria, J P Spano
BACKGROUND: Preclinical studies suggest synergistic antitumour effects of mammalian target of rapamycin (mTOR) inhibitor such as temsirolimus combined with anti-EGFR monoclonal antibody such as cetuximab. METHODS: Temsirolimus (T) and cetuximab (C) were combined and escalated in cohorts of patients with advanced or metastatic solid tumours, respectively from 15 to 25 mg and 150-250 mg/m(2), until the maximum tolerated dose (MTD) was determined. Effort was made in the expansion cohort to enrol patients harbouring a molecular aberration in the human epidermal growth factor receptor (EGFR) and/or phosphoinositide 3-kinase (PI3K) pathways...
June 12, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28616837/a-phase-ib-study-of-everolimus-combined-with-metformin-for-patients-with-advanced-cancer
#16
Remco J Molenaar, Tim van de Venne, Mariëtte J Weterman, Ron A Mathot, Heinz-Josef Klümpen, Dick J Richel, Johanna W Wilmink
Background The efficacy to monotherapy with the mTOR inhibitor everolimus in advanced cancer is often limited due to therapy resistance. Combining everolimus with metformin may decrease the chance of therapy resistance. Methods Patients received everolimus and metformin in a 3 + 3 dose-escalation scheme. Objectives were to determine the dose-limiting toxicities (DLTs), maximum tolerated dose, toxic effects, pharmacokinetics and anti-tumour efficacy. Results 9 patients received study treatment for a median duration of 48 days (range: 4-78)...
June 15, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28614791/human-vaccination-against-plasmodium-vivax-duffy-binding-protein-induces-strain-transcending-antibodies
#17
Ruth O Payne, Sarah E Silk, Sean C Elias, Kathryn H Milne, Thomas A Rawlinson, David Llewellyn, A Rushdi Shakri, Jing Jin, Geneviève M Labbé, Nick J Edwards, Ian D Poulton, Rachel Roberts, Ryan Farid, Thomas Jørgensen, Daniel Gw Alanine, Simone C de Cassan, Matthew K Higgins, Thomas D Otto, James S McCarthy, Willem A de Jongh, Alfredo Nicosia, Sarah Moyle, Adrian Vs Hill, Eleanor Berrie, Chetan E Chitnis, Alison M Lawrie, Simon J Draper
BACKGROUND: Plasmodium vivax is the most widespread human malaria geographically; however, no effective vaccine exists. Red blood cell invasion by the P. vivax merozoite depends on an interaction between the Duffy antigen receptor for chemokines (DARC) and region II of the parasite's Duffy-binding protein (PvDBP_RII). Naturally acquired binding-inhibitory antibodies against this interaction associate with clinical immunity, but it is unknown whether these responses can be induced by human vaccination...
June 15, 2017: JCI Insight
https://www.readbyqxmd.com/read/28612018/treatment-options-in-oligometastatic-disease-stereotactic-body-radiation-therapy-focus-on-colorectal-cancer
#18
REVIEW
Aaron T Wild, Yoshiya Yamada
BACKGROUND: Improvements in systemic therapy for metastatic colorectal cancer (CRC) have markedly extended survival, rendering local control of metastases to critical organs of increasing importance, especially in the oligometastatic setting where the disease may not yet have acquired the ability to widely disseminate. While surgical resection remains the gold standard for oligometastases in many organs, stereotactic body radiation therapy (SBRT) presents a non-invasive alternative for achieving local control...
March 2017: Visceral Medicine
https://www.readbyqxmd.com/read/28611198/phase-i-dose-escalation-and-expansion-study-of-the-braf-inhibitor-encorafenib-lgx818-in-metastatic-braf-mutant-melanoma
#19
Jean-Pierre Delord, Caroline Robert, Marta Nyakas, Grant A McArthur, Ragini Kudchakar, Amit Mahipal, Yasuhide Yamada, Ryan J Sullivan, Ana Arance, Richard F Kefford, Matteo S Carlino, Manuel Hidalgo, Carlos Gomez-Roca, Daniela Michel, Abdelkader Seroutou, Vassilios Aslanis, Giordano Caponigro, Darrin Stuart, Laure Moutouh-de Parseval, Tim Demuth, Reinhard Dummer
Purpose: Encorafenib, a selective BRAF-inhibitor (BRAFi), has a pharmacological profile that is distinct from that of other clinically active BRAFis. We evaluated encorafenib in a phase I study in patients with BRAFi treatment-naive and pretreated BRAF-mutant melanoma. <p>Experimental Design: The pharmacological activity of encorafenib was first characterized preclinically. Encorafenib monotherapy was then tested across a range of once-daily (QD; 50-700mg) or twice-daily (75-150mg) regimens in a phase I, open-label, dose-escalation and -expansion study in adult patients with histologically confirmed advanced/metastatic BRAF-mutant melanoma...
June 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28608776/short-term-effectiveness-of-a-community-implemented-falls-prevention-referral-service
#20
Andrea Christoforou, Marietta L van der Linden, Pelagia Koufaki
PURPOSE: To evaluate the effectiveness of the 16-week evidence-based Steady Steps exercise referral scheme at improving physical function, balance confidence, and quality of life (QoL) of community-dwelling older adults at risk of falling. METHOD: A non-experimental, practice-based study involving a retrospective analysis of participant outcomes. Pre-post comparisons of three performance-based measures of gait and balance and of person-reported outcomes for balance confidence and QoL were performed...
June 13, 2017: Disability and Rehabilitation
keyword
keyword
42481
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"