Day 1 :
Norwegian University of Life Science, Oslo Norway
Keynote: BP-C1 in treatment of metastatic breast cancer: A randomised, double blinded and placebo controlled clinical study
Time : 09:00-09:25
Stig Larsen has completed his DSc in Clinical Research Methodology at Ullevål Hospital, Oslo University, Norway. He is Professor at the Norwegian University ofrnLife Science and has published more than 300 papers in international medical and clinical research methodological journals.
Aim: The aim was to compare the efficacy and tolerability of a new benzene-poly-carboxylic acids complex with cisdiammineplatiumrn(II) (BP-C1) versus equal looking placebo in treatment of metastatic breast cancer patients.
Material & Methods: A randomized, double blind, placebo controlled multi-center study was performed with semi-cross-overrndesign. Patients allocated to placebo switches to BP-C1 after 32 days of treatment. Thirty patients were given daily intramuscularrninjection of 0.035 mg/kg bw BP-C1 or placebo in 32 days. Biochemistry, hematology, NCI Bethesda (CTC-NCI), EORTCrnQOL-C30 & BR23 recorded at screening and after every 16 days of treatment. CT performed at screening and every 32nd day.rnResults: The sum of target lesions increased 2.4% in the BP-C1 group and 14.3% in placebo. The increase in the placebo grouprnwas significant (p=0.013) but not in BP-C1. The difference between the group was significant in favor of BP-C1 (p=0.04).rnSignificant difference (p=0.026) in favor of BP-C1 regarding RECIST classification. CTC-NCI toxicity score increased nonsignificantlyrnin the BP-C1 group, but significantly in placebo (p=0.05). “Breast cancer related pain and discomfort” and “Breastrncancer treatment problem last week” were significantly reduced (p=0.02) in the BP-C1 group and slightly increased in placebo.rnSignificant difference in favor of BP-C1 (p=0.05). “Breast cancer treatment problem last week” was significantly reduced in thernBP-C1 group (p=0.02) and slightly increased in placebo. “Breast cancer related pain and discomfort”.rnConclusion: BP-C1 reduces the cancer growth, is well tolerated, improves quality-of-life and has few mainly mild AE inrnpatients suffering from stage IV MBC
Chapman University School of Pharmacy, USA
Keynote: Pharmacodynamic Profiling of Antibiotics Used in the Treatment of MRSA-Infected ICU Patients
Time : 09:25-09:50
Ayman M Noreddin received his PhD in Pharmaceutical Sciences from the University of the Pacific, California and received research training as a visiting scholarrnat the Department of Medicine, Stanford University. He had Post-doctoral fellowship (Pharmacokinetics and Pharmacodynamics of Antimicrobials), Departmentrnof Medical Microbiology, University of Manitoba followed by an American College of Clinical Pharmacy postdoctoral fellowship (Infectious Diseases). His researchrninterest includes Pharmacoklinetic/Pharmacodynamic modeling of anti-infective and anti-cancer therapy, clinical simulation and Monte Carlo analysis and bacterial resistance in biofilm studies. He has outstanding records of scientific and academic accomplishments with multiple research funding, numerous publications inrnhighly prestigious journals and various presentations in both national and international conferences. He served as a Scientific Reviewer for the NIH as well as otherrnnational and international research institutions.
Background: Appropriate initial treatment choices for methicillin resistant Staphylococcus aureus (MRSA) infections are veryrncritical especially in the intensive care units (ICU) settings. The aim of this study was to compare the ability of ceftobiprole,rndalbavancin, daptomycin, tigecycline, linezolid and vancomycin to achieve their requisite pharmacokinetic/pharmacodynamicrn(PK/PD) targets against MRSA isolates collected from ICU settings.
Methods: Monte Carlo Simulations were performed to simulate the PK/PD indices of the investigated antimicrobials. Probability of target attainment (PTA) was estimated at MIC values ranging from 0.03-32 μg/ml to define the PK/PD susceptibility breakpoints. Cumulative fraction of response (CFR) was computed using MIC data from the Canadian National Intensive Care Unit (CAN-ICU) study. Results: Analysis of the simulation results suggested the breakpoints of 8 μg/ml for ceftobiprole, 0.12 μg/ml for dalbavancin,daptomycin and tigecycline, and 1 μg/ml for linezolid and vancomycin. The estimated CFR were 100, 100, 70.8, 87.6, 88.7,rn82.4, 89.4, 98.3 % for ceftobiprole, dalbavancin, daptomycin (4mg/kg/day), daptomycin (6mg/kg/day), linezolid, tigecycline,vancomycin (1gm BID) and vancomycin (1.5gm BID), respectively.
Conclusions: Ceftobiprole and dalbavancin have the highest probability of achieving favorable outcome against MRSArninfections in the ICU. The susceptibility results suggested a further reduction of the vancomycin breakpoint to 1 μg/ml.
Keywords: MRSA, Monte-Carlo simulation, ceftobiprole, dalbavancin, vancomycin