NDLI: Lower Exposure and Faster Clearance of Bevacizumab in Gastric Cancer and the Impact of Patient Variables: Analysis of Individual Data from AVAGAST Phase III Trial

Content Provider	Springer Nature Link
Author	Han, Kelong Jin, Jin Maia, Mauricio Lowe, John Sersch, Martina A. Allison, David E.
Copyright Year	2014
Abstract	Altered pharmacokinetics of antibody drugs has been reported in advanced gastric cancer (AGC). We aim to evaluate bevacizumab pharmacokinetics in AGC from the Phase III trial (AVAGAST), and explore the influence of patient variables. Bevacizumab concentrations (Cp) were measured in plasma samples taken following disease progression from 162 patients (7.5 mg/kg every 3 weeks). Predicted Cp [median and 90% prediction interval] was simulated using the population pharmacokinetic model established for other cancers (PPK model) and compared to observed Cp. Bevacizumab clearance was estimated using NONMEM and compared between subgroups. Patient characteristics of AGC are similar to other cancers except for lower body weight despite higher percentage of males. Eighty-five percent of observed Cp was below the median predicted Cp and 38% below the lower boundary of the 90% prediction interval. Median bevacizumab clearance in AGC was 4.5 versus 3 mL/day/kg in other cancers. Bevacizumab clearance was significantly faster (p < 0.05) in patients without gastrectomy (n = 42) or lower albumin. Clearance appeared to be faster in patients with lower total protein, higher ECOG scores, more metastatic sites, and poorer response. No significant difference in bevacizumab concentrations and clearance was observed between Asian and Non-Asian patients. AGC patients exhibited significantly lower bevacizumab exposure due to an approximate 50% increase in clearance versus other cancers. Bevacizumab is cleared faster in patients without prior gastrectomy. No significant difference in bevacizumab pharmacokinetics was observed between Asian and Non-Asian patients. The underlying mechanism for faster bevacizumab clearance in AGC is unknown and warrants further research.
Starting Page	1056
Ending Page	1063
Page Count	8
File Format	PDF
ISSN	12341234
Journal	The AAPS Journal
Volume Number	16
Issue Number	5
e-ISSN	15507416
Language	English
Publisher	Springer US
Publisher Date	2014-06-19
Publisher Institution	American Association of Pharmaceutical Scientists
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	advanced gastric cancer bevacizumab ethnicity NONMEM pharmacokinetics Pharmacology/Toxicology Biochemistry Biotechnology Pharmacy
Content Type	Text
Resource Type	Article

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Lower Exposure and Faster Clearance of Bevacizumab in Gastric Cancer and the Impact of Patient Variables: Analysis of Individual Data from AVAGAST Phase III Trial

Lower Exposure and Faster Clearance of Bevacizumab in Gastric Cancer and the Impact of Patient Variables: Analysis of Individual Data from AVAGAST Phase III Trial

Population pharmacokinetics/pharmacodynamics of anesthetics

Evaluation of Angiopoietin-2 as a biomarker in gastric cancer: results from the randomised phase III AVAGAST trial

Phase I study of enzastaurin and bevacizumab in patients with advanced cancer: safety, efficacy and pharmacokinetics

Pharmacokinetics/pharmacodynamics and the stages of drug development: Role of modeling and simulation

Preparation and ocular pharmacokinetics of ganciclovir liposomes

Population pharmacokinetic and pharmacodynamic analysis of tesamorelin in HIV-infected patients and healthy subjects

Impact of Glycation on Antibody Clearance

Lower Exposure and Faster Clearance of Bevacizumab in Gastric Cancer and the Impact of Patient Variables: Analysis of Individual Data from AVAGAST Phase III Trial

Similar Documents

Lower Exposure and Faster Clearance of Bevacizumab in Gastric Cancer and the Impact of Patient Variables: Analysis of Individual Data from AVAGAST Phase III Trial

Lower Exposure and Faster Clearance of Bevacizumab in Gastric Cancer and the Impact of Patient Variables: Analysis of Individual Data from AVAGAST Phase III Trial

Population pharmacokinetics/pharmacodynamics of anesthetics

Evaluation of Angiopoietin-2 as a biomarker in gastric cancer: results from the randomised phase III AVAGAST trial

Phase I study of enzastaurin and bevacizumab in patients with advanced cancer: safety, efficacy and pharmacokinetics

Pharmacokinetics/pharmacodynamics and the stages of drug development: Role of modeling and simulation

Preparation and ocular pharmacokinetics of ganciclovir liposomes

Population pharmacokinetic and pharmacodynamic analysis of tesamorelin in HIV-infected patients and healthy subjects

Impact of Glycation on Antibody Clearance

Lower Exposure and Faster Clearance of Bevacizumab in Gastric Cancer and the Impact of Patient Variables: Analysis of Individual Data from AVAGAST Phase III Trial