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First-line liposomal irinotecan with oxaliplatin, 5-fluorouracil and leucovorin (NALIRIFOX) in pancreatic ductal adenocarcinoma: A phase I/II study.

Eur J Cancer 2021 May 3;151:14-24. Epub 2021 May 3.

St John of God Subiaco Hospital, Subiaco, WA, Australia.

Background: This open-label, phase I/II study evaluated safety and efficacy for first-line liposomal irinotecan + oxaliplatin + 5-fluorouracil + leucovorin (NALIRIFOX).

Methods: Patients (aged ≥18 years) had locally advanced/metastatic pancreatic ductal adenocarcinoma (mPDAC), with an Eastern Cooperative Oncology Group performance status score of 0/1 and adequate organ function. Primary objectives were to determine the maximum tolerated dose (MTD) and to evaluate safety and tolerability. Read More

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Mortality and AIDS-defining events among young people following transition from paediatric to adult HIV care in the UK.

HIV Med 2021 May 3. Epub 2021 May 3.

MRC Clinical Trials Unit at UCL, University College London (UCL), London, UK.

Objectives: To investigate risk of AIDS and mortality after transition from paediatric to adult care in a UK cohort of young people with perinatally acquired HIV.

Methods: Records of people aged ≥ 13 years on 31 December 2015 in the UK paediatric HIV cohort (Collaborative HIV Paediatric Study) were linked to those of adults in the UK Collaborative HIV Cohort (CHIC) cohort. We calculated time from transition to a new AIDS event/death, with follow-up censored at the last visit or 31 December 2015, whichever was the earliest. Read More

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Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.

Authors:

Lancet 2021 May;397(10285):1637-1645

Background: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation.

Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg-800 mg (depending on weight) given intravenously. Read More

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Validation of a Commercial Reagent for the Depletion of Biotin from Serum/Plasma: A Rapid and Simple Tool to Detect Biotin Interference with Immunoassay Testing.

J Appl Lab Med 2021 Apr 28. Epub 2021 Apr 28.

Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.

Background: It is important for clinical laboratories to have protocols for investigating suspected biotin interference in patient samples. VeraPrep Biotin™ is a commercial product used to rapidly deplete biotin from serum/plasma samples. The objectives of this study were to verify that VeraPrep Biotin™: (a) does not impact immunoassay analyte recovery in control samples and (b) can effectively deplete biotin from samples (both biotin-spiked and samples from donors who ingested biotin supplements). Read More

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ATLAS trial of adjuvant axitinib in patients with renal cell carcinoma: subgroup analyses with focus on axitinib dosing and racial groups.

ESMO Open 2021 Apr 23;6(3):100105. Epub 2021 Apr 23.

Department of Medical Oncology, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.

Background: The ATLAS trial, investigating adjuvant axitinib versus placebo in renal cell carcinoma (RCC), was stopped for futility at a preplanned interim analysis. We report subgroup outcome analyses by ethnicity, time on treatment, dose modification and toxicity.

Patients And Methods: Patient demographics, baseline characteristics, treatment duration and exposure and safety were analysed for Asian versus non-Asian patients treated with axitinib versus placebo. Read More

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Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial.

Lancet Oncol 2021 05 13;22(5):702-715. Epub 2021 Apr 13.

Hôpital Nord Franche-Comté, Montbéliard, France; University Hospital of Besançon, Besançon, France.

Background: Treatment of locally advanced rectal cancer with chemoradiotherapy, surgery, and adjuvant chemotherapy controls local disease, but distant metastases remain common. We aimed to assess whether administering neoadjuvant chemotherapy before preoperative chemoradiotherapy could reduce the risk of distant recurrences.

Methods: We did a phase 3, open-label, multicentre, randomised trial at 35 hospitals in France. Read More

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Reduction of anterior uveitis flares in patients with axial spondyloarthritis on certolizumab pegol treatment: final 2-year results from the multicenter phase IV C-VIEW study.

Ther Adv Musculoskelet Dis 2021 29;13:1759720X211003803. Epub 2021 Mar 29.

Clinic for Internal Medicine and Rheumatology, Klinikum Bielefeld and Department of Gastroenterology, Infectiology and Rheumatology, Charité Berlin, Germany.

Introduction: Acute anterior uveitis (AAU), affecting up to 40% of patients with axial spondyloarthritis (axSpA), risks permanent visual deficits if not adequately treated. We report 2-year results from C-VIEW, the first study to prospectively investigate certolizumab pegol (CZP) on AAU in patients with active axSpA at high risk of recurrent AAU.

Patients And Methods: C-VIEW (NCT03020992) was a 104-week (96 weeks plus 8-week safety follow-up), open-label, multicenter study. Read More

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Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): a phase 3, open-label, randomised, controlled trial.

Lancet Oncol 2021 05 30;22(5):690-701. Epub 2021 Mar 30.

Department of Medical Oncology, The Christie NHS Foundation Trust/Institute of Cancer Sciences, University of Manchester, Manchester, UK; Division of Cancer Sciences, University of Manchester, Manchester, UK. Electronic address:

Background: Advanced biliary tract cancer has a poor prognosis. Cisplatin and gemcitabine is the standard first-line chemotherapy regimen, but no robust evidence is available for second-line chemotherapy. The aim of this study was to determine the benefit derived from second-line FOLFOX (folinic acid, fluorouracil, and oxaliplatin) chemotherapy in advanced biliary tract cancer. Read More

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Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials.

Lancet Diabetes Endocrinol 2021 05 30;9(5):276-292. Epub 2021 Mar 30.

Jikei University School of Medicine, Tokyo, Japan.

Background: A 2017 meta-analysis of data from 25 randomised controlled trials (RCTs) of vitamin D supplementation for the prevention of acute respiratory infections (ARIs) revealed a protective effect of this intervention. We aimed to examine the link between vitamin D supplementation and prevention of ARIs in an updated meta-analysis.

Methods: For this systematic review and meta-analysis, we searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and the ClinicalTrials. Read More

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First-line palliative systemic therapy alternated with electrostatic pressurised intraperitoneal aerosol chemotherapy (oxaliplatin) for isolated unresectable colorectal peritoneal metastases: protocol of a multicentre, single-arm, phase II study (CRC-PIPAC-II).

BMJ Open 2021 Mar 30;11(3):e044811. Epub 2021 Mar 30.

Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands

Introduction: Despite its increasing use, first-line palliative systemic therapy alternated with electrostatic pressurised intraperitoneal aerosol chemotherapy with oxaliplatin (ePIPAC-OX), hereinafter referred to as first-line bidirectional therapy, has never been prospectively investigated in patients with colorectal peritoneal metastases (CPM). As a first step to address this evidence gap, the present study aims to assess the safety, feasibility, antitumour activity, patient-reported outcomes, costs and systemic pharmacokinetics of first-line bidirectional therapy in patients with isolated unresectable CPM.

Methods And Analysis: In this single-arm, phase II study in two Dutch tertiary referral centres, 20 patients are enrolled. Read More

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Cost-effectiveness of oral semaglutide added to current antihyperglycemic treatment for type 2 diabetes.

J Manag Care Spec Pharm 2021 Apr;27(4):455-468

The Comparative Health Outcomes, Policy, and Economics (CHOICE) Institute, Department of Pharmacy, University of Washington, Seattle.

Oral semaglutide is the first oral formulation of a glucagon-like peptide 1 (GLP-1) receptor agonist to be approved in the United States for glycemic control in people with type 2 diabetes mellitus (T2DM). While oral semaglutide is not indicated for reduction of cardiovascular event risk, its label does include evidence of no increase in cardiovascular risk in people who received oral semaglutide. To estimate the incremental value of oral semaglutide added to existing antihyperglycemic treatment for people with T2DM with additional risk for cardiovascular disease. Read More

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Prognostic significance of the HFA-PEFF score in patients with heart failure with preserved ejection fraction.

ESC Heart Fail 2021 Mar 24. Epub 2021 Mar 24.

Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.

Aims: The HFA-PEFF score is a part of the stepwise diagnostic algorithm of heart failure with preserved ejection fraction (HFpEF). We aimed to evaluate the prognostic significance of the HFA-PEFF score on the clinical outcomes in patients with HFpEF.

Methods And Results: The Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with preserved Ejection Fraction (PURSUIT-HFpEF) study is a prospective, multicentre, observational study in which collaborating hospitals in Osaka record clinical, echocardiographic, and outcome data of patients with acute decompensated heart failure with preserved left ventricular ejection fraction (≥50%) [UMIN-CTR ID: UMIN000021831]. Read More

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Impact of Oseltamivir Treatment on Influenza A and B Virus Dynamics in Human Volunteers.

Front Microbiol 2021 1;12:631211. Epub 2021 Mar 1.

Genome Science and Technology, University of Tennessee, Knoxville, TN, United States.

Influenza viruses infect millions of humans every year causing an estimated 400,000 deaths globally. Due to continuous virus evolution current vaccines provide only limited protection against the flu. Several antiviral drugs are available to treat influenza infection, and one of the most commonly used drugs is oseltamivir (Tamiflu). Read More

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Influence of BRAF and PIK3CA mutations on the efficacy of FOLFIRI plus bevacizumab or cetuximab as first-line therapy in patients with RAS wild-type metastatic colorectal carcinoma and <3 baseline circulating tumour cells: the randomised phase II VISNÚ-2 study.

ESMO Open 2021 Apr 10;6(2):100062. Epub 2021 Mar 10.

Medical Oncology, Hospital Clínico San Carlos, Instituto de Investigación Hospital Clínico San Carlos (IdISSC), CIBERONC, Madrid, Spain.

Background: We explored the influence of BRAF and PIK3CA mutational status on the efficacy of bevacizumab or cetuximab plus 5-fluorouracil/leucovorin and irinotecan (FOLFIRI) as first-line therapy in patients with RAS wild-type metastatic colorectal cancer (mCRC).

Patients And Methods: VISNÚ-2 was a multicentre, randomised, phase II study. Patients with RAS wild-type mCRC and <3 circulating tumour cells/7. Read More

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Factors Associated With Elevated N-Terminal Pro B-Type Natriuretic Peptide Concentrations at the Convalescent Stage and 1-Year Outcomes in Patients With Heart Failure With Preserved Ejection Fraction.

Circ Rep 2020 Jul 7;2(8):400-408. Epub 2020 Jul 7.

Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine Suita Japan.

Little is known about factors associated with elevated N-terminal pro B-type natriuretic peptide (NT-proBNP) at the convalescent stage and their effects on 1-year outcomes in patients with heart failure with preserved ejection fraction (HFpEF). This study included 469 patients with HFpEF. Elevated NT-proBNP was defined as the highest quartile. Read More

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Distribution and determinants of serum high-sensitivity C-reactive protein in Ethiopian population.

Clin Chim Acta 2021 Jun 4;517:99-107. Epub 2021 Mar 4.

National Reference Laboratory for Clinical Chemistry, Ethiopian Public Health Institute, Addis Ababa, Ethiopia.

Background: C-reactive protein (CRP) is an important inflammatory marker associated with different disease conditions, and its concentration differs among ethnicity. This study aimed to determine the distribution and determinants of serum high-sensitive method CRP (hsCRP) that can measure the typically low concentrations, among the Ethiopian population, for which there is no data.

Methods: A cross-sectional community-based study was conducted in April-June 2015. Read More

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Experimental and theoretical study of photo-dissociation spectroscopy of pyrene dimer radical cations stored in a compact electrostatic ion storage ring.

Phys Chem Chem Phys 2021 Mar;23(10):6017-6028

Laboratoire de Chimie et de Physique Quantiques (LCPQ), IRSAMC, Université de Toulouse (UPS) and CNRS, 118 Route de Narbonne, F-31062 Toulouse, France.

In this paper, we present an experimental and theoretical study of the photo-dissociation of free-flying dimer radical cations of pyrene (C16H10)2+. Experimentally, the dimers were produced in the plasma of an electron cyclotron resonance ion source and stored in an electrostatic ion storage ring, the Mini-Ring for times up to 10 ms and the photo-dissociation spectrum was recorded in the 400 to 2000 nm range. Two broad absorption bands were observed at 550 (2. Read More

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Visible light. Part II: Photoprotection against visible and ultraviolet light.

J Am Acad Dermatol 2021 May 25;84(5):1233-1244. Epub 2021 Feb 25.

Department of Dermatology, Photomedicine and Photobiology Unit, Henry Ford Health System, Detroit, Michigan.

Cutaneous photobiology studies have focused primarily on the ultraviolet portion of the solar spectrum. Visible light (VL), which comprises 50% of the electromagnetic radiation that reaches the Earth's surface and, as discussed in Part I of this CME, has cutaneous biologic effects, such as pigment darkening and erythema. Photoprotection against VL includes avoiding the sun, seeking shade, and using photoprotective clothing. Read More

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Visible light. Part I: Properties and cutaneous effects of visible light.

J Am Acad Dermatol 2021 May 25;84(5):1219-1231. Epub 2021 Feb 25.

Department of Dermatology, SUNY Downstate Medical Center, Brooklyn, New York; Dermatology Service, VA New York Harbor Healthcare System, Brooklyn Campus, Brooklyn, New York. Electronic address:

Approximately 50% of the sunlight reaching the Earth's surface is visible light (400-700 nm). Other sources of visible light include lasers, light-emitting diodes, and flash lamps. Photons from visible light are absorbed by photoreceptive chromophores (e. Read More

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Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19.

N Engl J Med 2021 04 25;384(16):1491-1502. Epub 2021 Feb 25.

From Imperial College London (A.C.G., F.A.-B.), Imperial College Healthcare NHS Trust, St. Mary's Hospital (A.C.G.), Intensive Care National Audit and Research Centre (P.R.M., K.M.R.), University College London Hospital (R.H.), King's College London (M.S.-H.), and Guy's and St. Thomas' NHS Foundation Trust (M.S.-H.), London, University of Oxford (A. Beane) and NHS Blood and Transplant (L.J.E.), Oxford, and University of Bristol, Bristol (C.A.B.) - all in the United Kingdom; Monash University (A.D.N., A. Buzgau, A.C.C., A.M.H., S.P.M., J.C.P., C.G., S.A.W.) and Alfred Health (A.D.N., A.C.C.), Melbourne, VIC, Fiona Stanley Hospital (E. Litton, K.O.) and University of Western Australia (E. Litton), Perth, WA, University of Sydney and Royal Prince Alfred Hospital, Sydney (A.E.P.), and St. John of God Hospital, Subiaco, WA (S.A.W.) - all in Australia; University College Dublin, Dublin (A.D.N.); King Saud bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, Riyadh, Saudi Arabia (Y.M.A.); Hospital Raymond Poincaré (Assistance Publique-Hôpitaux de Paris) and Université Paris Saclay-Université de Versailles Saint-Quentin-en-Yvelines-INSERM, Garches, and Université de Versailles Saint-Quentin-en-Yvelines-Université Paris Saclay, Montigny-le-Bretonneux - all in France (D.A.); University Medical Center Utrecht, Utrecht (W.B.-P., M.J.M.B., H.L.L., E.R., L.P.G.D.), and Radboudumc, Nijmegen (F.L.V.) - both in the Netherlands; Berry Consultants, Austin, TX (L.R.B., M.A.D., M.F., E. Lorenzi, A.M., C.T.S., R.J.L., S.B.); St. Michael's Hospital Unity Health (Z.B., J.C.M., M.S.S.) and University Health Network and University of Toronto (P.R.L.), Toronto, Université de Sherbrooke, Sherbrooke, QC (F.L.), University of British Columbia, Vancouver (S.M.), University of Alberta, Edmonton (W.I.S.), Université Laval, Québec City (A.F.T.), and University of Manitoba, Winnipeg, MB (R.Z.) - all in Canada; Jena University Hospital, Jena, Germany (F.M.B.); Auckland City Hospital (E.J.D., T.E.H., S.P.M., R.L.P., C.J.M.), Middlemore Hospital (S.C.M.), and University of Auckland (R.L.P.), Auckland, and Medical Research Institute of New Zealand, Wellington (T.E.H., S.P.M., A.M.T.) - all in New Zealand; University of Antwerp, Wilrijk, Belgium (H.G.); University of Oxford, Bangkok, Thailand (R.H.); National Intensive Care Surveillance, Colombo, Sri Lanka (R.H.); UPMC Children's Hospital of Pittsburgh (C.M.H.) and University of Pittsburgh (K.M.L., F.B.M., B.J.M., S.K.M., C.W.S., D.C.A.), Pittsburgh; Queen's University Belfast and Royal Victoria Hospital, Belfast, Northern Ireland (D.F.M.); University of Helsinki and Helsinki University Hospital, Helsinki (V.P.); and Harbor-UCLA Medical Center, Torrance, CA (R.J.L.).

Background: The efficacy of interleukin-6 receptor antagonists in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear.

Methods: We evaluated tocilizumab and sarilumab in an ongoing international, multifactorial, adaptive platform trial. Adult patients with Covid-19, within 24 hours after starting organ support in the intensive care unit (ICU), were randomly assigned to receive tocilizumab (8 mg per kilogram of body weight), sarilumab (400 mg), or standard care (control). Read More

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Emicizumab prophylaxis in haemophilia patients older than 50 years with cardiovascular risk factors: Real-world data.

Haemophilia 2021 Mar 17;27(2):253-260. Epub 2021 Feb 17.

National Hemophilia Center, Sheba Medical center, Tel Hashomer, Israel.

Introduction: Emicizumab (Hemlibra™) is approved for prophylaxis of Haemophilia A (HA) patients with and without inhibitors. However, real-world data on emicizumab use in the elderly HA patients with concomitant cardiovascular risk factors are lacking.

Aim: To evaluate the safety and efficacy of emicizumab in a real-world cohort of elderly HA patients. Read More

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The Acetylcholine-Activated Potassium Current Inhibitor XAF-1407 Terminates Persistent Atrial Fibrillation in Goats.

Front Pharmacol 2020 27;11:608410. Epub 2021 Jan 27.

Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht, Netherlands.

The acetylcholine-activated inward rectifier potassium current (I) has been proposed as an atrial-selective target for the treatment of atrial fibrillation (AF). Using a novel selective I inhibitor XAF-1407, the study investigates the effect of I inhibition in goats with pacing-induced, short-term AF. Ten goats (57 ± 5 kg) were instrumented with pericardial electrodes. Read More

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January 2021

Budesonide/Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler Improves Exacerbation Outcomes in Patients with COPD without a Recent Exacerbation History: A Subgroup Analysis of KRONOS.

Int J Chron Obstruct Pulmon Dis 2021 28;16:179-189. Epub 2021 Jan 28.

AstraZeneca, Morristown, NJ, USA.

Purpose: In the Phase III, 24-week KRONOS study (NCT02497001), triple therapy with budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI) reduced exacerbation rates versus glycopyrrolate/formoterol fumarate (GFF) MDI in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD) and no requirement for a history of exacerbations. We report a post hoc analysis investigating whether the benefits observed were driven by patients with ≥1 exacerbation in the 12 months prior to the study.

Patients And Methods: Patients received BGF MDI 320/18/9. Read More

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January 2021

Severe asthma: adding new evidence - Latin American Thoracic Society.

ERJ Open Res 2021 Jan 18;7(1). Epub 2021 Jan 18.

A2DAHT Iberoamerican Agency for Development and Assessment of Health Technology, Mexico, DF, Mexico.

This document constitutes a summary of the clinical practice guidelines (CPGs) prepared at the initiative of the Latin American Thoracic Society (ALAT). Due to new evidence in the treatment of severe asthma, it was agreed to select six clinical questions, and the corresponding recommendations are provided herein. After considering the quality of the evidence, the balance between desirable and undesirable impacts and the feasibility and acceptance of procedures, the following recommendations were established. Read More

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January 2021

Phase I Study of Elacestrant (RAD1901), a Novel Selective Estrogen Receptor Degrader, in ER-Positive, HER2-Negative Advanced Breast Cancer.

J Clin Oncol 2021 Apr 29;39(12):1360-1370. Epub 2021 Jan 29.

University of Colorado, Aurora, CO.

Purpose: This phase I study (RAD1901-005; NCT02338349) evaluated elacestrant, an investigational oral selective estrogen receptor degrader (SERD), in heavily pretreated women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer, including those with estrogen receptor gene alpha () mutation. The primary objective was to determine the maximum tolerated dose and/or recommended phase II dose (RP2D).

Methods: The study consisted of a 3 + 3 design (elacestrant capsules) followed by expansion at RP2D (400-mg capsules, then 400-mg tablets) for the evaluation of safety and antitumor activity. Read More

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Long-term outcome of imatinib 400 mg compared to imatinib 600 mg or imatinib 400 mg daily in combination with cytarabine or pegylated interferon alpha 2a for chronic myeloid leukaemia: results from the French SPIRIT phase III randomised trial.

Leukemia 2021 Jan 22. Epub 2021 Jan 22.

Inserm CIC 1427, Université de Paris, Paris, France.

The STI571 prospective randomised trial (SPIRIT) French trial is a four-arm study comparing imatinib (IM) 400 mg versus IM 600 mg, IM 400 mg + cytarabine (AraC), and IM 400 mg + pegylated interferon alpha2a (PegIFN-α2a) for the front-line treatment of chronic-phase chronic myeloid leukaemia (CML). Long-term analyses included overall and progression-free survival, molecular responses to treatment, and severe adverse events. Starting in 2003, the trial included 787 evaluable patients. Read More

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January 2021

Final analysis of the randomized trial on imatinib as an adjuvant in localized gastrointestinal stromal tumors (GIST) from the EORTC Soft Tissue and Bone Sarcoma Group (STBSG), the Australasian Gastro-Intestinal Trials Group (AGITG), UNICANCER, French Sarcoma Group (FSG), Italian Sarcoma Group (ISG), and Spanish Group for Research on Sarcomas (GEIS).

Ann Oncol 2021 04 19;32(4):533-541. Epub 2021 Jan 19.

Department of Medicine, NetSARC and LYRIC, Centre Leon Berard, Lyon, France.

Background: In 2004, we started an intergroup randomized trial of adjuvant imatinib versus no further therapy after R0-R1 surgery in localized, high/intermediate-risk gastrointestinal stromal tumors (GIST) patients. Interim analysis results were published in 2015 upon recommendation from an independent data review committee. We report the final outcome of the study. Read More

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Characterization of the pharmacokinetics of entrectinib and its active M5 metabolite in healthy volunteers and patients with solid tumors.

Invest New Drugs 2021 Jun 18;39(3):803-811. Epub 2021 Jan 18.

Roche Innovation Centre Welwyn, Roche Products Ltd, Welwyn Garden City, UK.

Background: Entrectinib is an oral, CNS-active, potent inhibitor of tyrosine receptor kinases A/B/C, tyrosine kinase ROS proto-oncogene 1, and anaplastic lymphoma kinase approved for use in patients with solid tumors. We describe 3 clinical studies, including one investigating the single/multiple dose pharmacokinetics of entrectinib in patients and two studies in healthy volunteers investigating the absorption/distribution/metabolism/excretion (ADME) of entrectinib, its relative bioavailability, and effect of food on pharmacokinetics.

Methods: The patient study is open-label with dose-escalation and expansion phases. Read More

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Avapritinib in Patients With Advanced Gastrointestinal Stromal Tumors Following at Least Three Prior Lines of Therapy.

Oncologist 2021 04 1;26(4):e639-e649. Epub 2021 Feb 1.

Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.

Background: Most gastrointestinal stromal tumors (GIST) driven by KIT or platelet-derived growth factor receptor A (PDGFRA) mutations develop resistance to available tyrosine kinase inhibitor (TKI) treatments. NAVIGATOR is a two-part, single-arm, dose escalation and expansion study designed to evaluate safety and antineoplastic activity of avapritinib, a selective, potent inhibitor of KIT and PDGFRA, in patients with unresectable or metastatic GIST.

Materials And Methods: Eligible patients were 18 years or older with histologically or cytologically confirmed unresectable GIST and Eastern Cooperative Oncology Group performance status ≤2 and initiated avapritinib at 300 mg or 400 mg once daily. Read More

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Sofosbuvir/velpatasvir with or without low-dose ribavirin for patients with chronic hepatitis C virus infection and severe renal impairment.

Gut 2021 Jan 6. Epub 2021 Jan 6.

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

Objective: Data regarding the real-world effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) with or without low-dose ribavirin (RBV) in patients with chronic hepatitis C virus (HCV) infection and severe renal impairment (RI) are limited. We evaluated the performance of SOF/VEL with or without low-dose RBV in HCV-infected patients with chronic kidney disease stage 4 or 5.

Design: 191 patients with compensated (n=181) and decompensated (n=10) liver diseases receiving SOF/VEL (400/100 mg/day) alone and SOF/VEL with low-dose RBV (200 mg/day) for 12 weeks were retrospectively recruited at 15 academic centres in Taiwan. Read More

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January 2021