Hyperglycemia in cancer and useage of TKI 's
Posted: Fri Mar 18, 2016 7:10 pm
Is this our first clue to ASPS rebound ?
Un treated hyperglycemia ?
Hyperglycemia, a Neglected Factor during Cancer Progression
Wanxing Duan,1 Xin Shen,2 Jianjun Lei,1 Qinhong Xu,1 Yongtian Yu,1 Rong Li,1 Erxi Wu,3 and Qingyong Ma1
1Department of Hepatobiliary Surgery, First Affiliated Hospital, Medical College, Xi’an Jiaotong University, 277 West Yanta Road, Xi’an, Shaanxi 710061, China
2Department of Anesthesiology, First Affiliated Hospital, Xi’an Jiaotong University, 277 West Yanta Road, Xi’an, Shaanxi 710061, China
3Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58105, USA
Received 3 December 2013; Revised 17 February 2014; Accepted 17 February 2014; Published 17 April 2014
Academic Editor: Robert A. Vierkant
Copyright © 2014 Wanxing Duan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
http://www.hindawi.com/journals/bmri/2014/461917/
http://tlcr.amegroups.com/article/view/5430
Article Abstract
Management of hyperglycemia from epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) targeting T790M-mediated resistance
Authors: Jeryl Villadolid, Jennifer L. Ersek, Mei Ka Fong, Lindsey Sirianno, Ellen S. Story
Abstract
Epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) patients are associated with sensitivity to small molecule tyrosine kinase inhibitors (TKIs) such as erlotinib, gefitinib, and afatinib. Although studies show an increased progression free survival (PFS) with use of EGFR TKIs in the first-line setting, most patients will develop resistance to therapy after the first 8-16 months. T790M is an acquired resistance mutation reported in 60-70% of patients who initially responded to a prior EGFR TKI. Recently, EGFR TKIs targeting T790M have been developed to overcome resistance with positive results in PFS and objective response rate in patients who have had disease progression on at least one TKI. Two EGFR TKIs targeting T790M, AZD9291 and rociletinib, are new active treatment options for NSCLC but differ in adverse effect profiles. Dose-limiting hyperglycemia has been reported with rociletinib and has required dose reduction, an oral antihyperglycemic, or both, without discontinuation of therapy. This suggests that patients may be effectively treated chronically for hyperglycemia associated with EGFR TKIs targeting T790M, however, guidelines for treatment of hyperglycemia in this setting have not been published. We discuss mechanisms of hyperglycemia associated with TKIs and initial management of hyperglycemia, including benefits and limitations of oral antihyperglycemic options, adjustment of therapy based on grade of hyperglycemia, and recommendations for follow-up glucose monitoring.
Un treated hyperglycemia ?
Hyperglycemia, a Neglected Factor during Cancer Progression
Wanxing Duan,1 Xin Shen,2 Jianjun Lei,1 Qinhong Xu,1 Yongtian Yu,1 Rong Li,1 Erxi Wu,3 and Qingyong Ma1
1Department of Hepatobiliary Surgery, First Affiliated Hospital, Medical College, Xi’an Jiaotong University, 277 West Yanta Road, Xi’an, Shaanxi 710061, China
2Department of Anesthesiology, First Affiliated Hospital, Xi’an Jiaotong University, 277 West Yanta Road, Xi’an, Shaanxi 710061, China
3Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58105, USA
Received 3 December 2013; Revised 17 February 2014; Accepted 17 February 2014; Published 17 April 2014
Academic Editor: Robert A. Vierkant
Copyright © 2014 Wanxing Duan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
http://www.hindawi.com/journals/bmri/2014/461917/
http://tlcr.amegroups.com/article/view/5430
Article Abstract
Management of hyperglycemia from epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) targeting T790M-mediated resistance
Authors: Jeryl Villadolid, Jennifer L. Ersek, Mei Ka Fong, Lindsey Sirianno, Ellen S. Story
Abstract
Epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) patients are associated with sensitivity to small molecule tyrosine kinase inhibitors (TKIs) such as erlotinib, gefitinib, and afatinib. Although studies show an increased progression free survival (PFS) with use of EGFR TKIs in the first-line setting, most patients will develop resistance to therapy after the first 8-16 months. T790M is an acquired resistance mutation reported in 60-70% of patients who initially responded to a prior EGFR TKI. Recently, EGFR TKIs targeting T790M have been developed to overcome resistance with positive results in PFS and objective response rate in patients who have had disease progression on at least one TKI. Two EGFR TKIs targeting T790M, AZD9291 and rociletinib, are new active treatment options for NSCLC but differ in adverse effect profiles. Dose-limiting hyperglycemia has been reported with rociletinib and has required dose reduction, an oral antihyperglycemic, or both, without discontinuation of therapy. This suggests that patients may be effectively treated chronically for hyperglycemia associated with EGFR TKIs targeting T790M, however, guidelines for treatment of hyperglycemia in this setting have not been published. We discuss mechanisms of hyperglycemia associated with TKIs and initial management of hyperglycemia, including benefits and limitations of oral antihyperglycemic options, adjustment of therapy based on grade of hyperglycemia, and recommendations for follow-up glucose monitoring.