title: The adverse events profile of anti-IGF-1R monoclonal antibodies in cancer therapy.
abstract: OBJECTIVE
  Insulin-like growth factor-1 receptor (IGF-1R) targeted therapies have become one of the intriguing areas in anticancer drug development during the last decade. As one of these therapies, anti-IGF-1R monoclonal antibodies (mAbs) are also advancing further in development. Our purpose was to conduct a systematic review of the adverse events (AEs) caused by anti-IGF-1R monoclonal antibodies in cancer therapy.
  
  
  METHODS
  We searched the term'IGF-1R monoclonal antibody' in the Pubmed database and found 389 related articles. After elaborate selection, 15 clinical studies that satisfied our criteria were then adopted for further analysis. We extracted all the useful information about the AEs of mAbs from the enrolled studies. Every kind of reported AE as well as corresponding incidences were summed up and calculated. We compared AE incidence differences in two age groups, and analyzed toxicities of mAbs used as a single agent or combined with chemotherapies. Finally, the differences of AE profiles between individual mAbs were also valued.
  
  
  RESULTS
  AEs were more severe in the lower age group and 13 of 19 AE incidences in the single-agent group were significantly lower than in the combination group (P < 0.05). R1507 seemed to show a worse AE profile than cixutumumab and figitumumab.
  
  
  CONCLUSIONS
  When anti-IGF-1R mAbs are used for cancer therapy, it is essential to choose the proper drug and combined chemotherapies to reduce AE occurrences. Also, administration of these mAbs to younger patients should be more carefully supervised. Furthermore, some more frequently observed AEs for specific mAb should be paid adequate attention.
authors.affiliation: Department of Thoracic Surgery, Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, China.
authors.forename: Honghai
authors.initials: H
authors.lastname: Ma
authors.forename: Tiehong
authors.initials: T
authors.lastname: Zhang
authors.forename: Hongchang
authors.initials: H
authors.lastname: Shen
authors.forename: Hongxin
authors.initials: H
authors.lastname: Cao
authors.forename: Jiajun
authors.initials: J
authors.lastname: Du
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D066126:Cardiotoxicity / Q000209:etiology; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced; D009369:Neoplasms / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced; D017526:Receptor, IGF Type 1 / Q000276:immunology*; D013921:Thrombocytopenia / Q000139:chemically induced
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C557414:cixutumumab; D017526:Receptor, IGF Type 1; C525021:figitumumab; C551399:teprotumumab
keywords: R1507; adverse events; anti-IGF-1R monoclonal antibody; cixutumumab; dalotuzumab; figitumumab
references.citation: J Clin Oncol. 2009 Dec 1;27(34):5800-7
references.pmid: 19786654
references.citation: Lancet. 1988 Nov 19;2(8621):1170-2
references.pmid: 2903379
references.citation: Clin Cancer Res. 2011 Sep 15;17(18):6052-60
references.pmid: 21750201
references.citation: Invest New Drugs. 2012 Aug;30(4):1548-56
references.pmid: 21748299
references.citation: J Clin Oncol. 2012 Jan 20;30(3):256-62
references.pmid: 22184397
references.citation: Curr Drug Targets. 2009 Oct;10(10):923-36
references.pmid: 19663769
references.citation: Mol Cancer Ther. 2008 Sep;7(9):2575-88
references.pmid: 18790742
references.citation: Curr Pharm Des. 2007;13(7):671-86
references.pmid: 17346183
references.citation: Cancer J. 2010 May-Jun;16(3):183-94
references.pmid: 20526094
references.citation: Diabetes. 2007 Jun;56(6):1638-46
references.pmid: 17363744
references.citation: Clin Cancer Res. 2010 Apr 15;16(8):2458-65
references.pmid: 20371689
references.citation: J Natl Cancer Inst. 2012 Jul 3;104(13):975-81
references.pmid: 22761272
references.citation: Clin Cancer Res. 2011 Feb 1;17(3):611-9
references.pmid: 21127194
references.citation: Expert Opin Biol Ther. 2010 Apr;10(4):575-85
references.pmid: 20175655
references.citation: J Thorac Oncol. 2012 Feb;7(2):419-26
references.pmid: 22237261
references.citation: J Clin Invest. 1997 May 15;99(10):2538-44
references.pmid: 9153298
references.citation: J Clin Oncol. 2014 Jul 1;32(19):2059-66
references.pmid: 24888810
references.citation: Clin Cancer Res. 2010 May 1;16(9):2512-7
references.pmid: 20388853
references.citation: J Clin Oncol. 2008 Jul 1;26(19):3196-203
references.pmid: 18474873
references.citation: Clin Lung Cancer. 2009 Jul;10(4):273-80
references.pmid: 19632947
references.citation: Lancet Oncol. 2010 Feb;11(2):129-35
references.pmid: 20036194
references.citation: J Clin Oncol. 2011 Dec 1;29(34):4541-7
references.pmid: 22025149
references.citation: Br J Cancer. 2010 Jul 27;103(3):332-9
references.pmid: 20628389
references.citation: J Clin Oncol. 2009 May 20;27(15):2516-22
references.pmid: 19380445
references.citation: Clin Cancer Res. 2011 Feb 15;17(4):871-9
references.pmid: 21177764
references.citation: Expert Opin Investig Drugs. 2009 Jul;18(7):1025-33
references.pmid: 19548856
references.citation: Biochem J. 2007 May 1;403(3):603-13
references.pmid: 17291192
references.citation: Clin Lung Cancer. 2009 Jul;10(4):262-72
references.pmid: 19632946
references.citation: Oncogene. 2009 Aug 27;28(34):3009-21
references.pmid: 19581933
references.citation: Clin Cancer Res. 2011 Oct 1;17(19):6304-12
references.pmid: 21810918
references.citation: J Clin Oncol. 2011 Dec 1;29(34):4574-80
references.pmid: 22025157
references.citation: J Clin Oncol. 2010 Sep 20;28(27):4240-6
references.pmid: 20713879
references.citation: J Thorac Oncol. 2009 Nov;4(11):1397-403
references.pmid: 19745765
references.citation: Invest New Drugs. 2012 Dec;30(6):2433-42
references.pmid: 22415797