title: Reaction of plasma adiponectin level in non-small cell lung cancer patients treated with EGFR-TKIs.
abstract: BACKGROUND
  Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are routinely used to treat advanced non-small cell lung cancer (NSCLC) patients with activated EGFR mutations, and are associated with excellent response and improvement of performance status. Adipose tissue produces and releases substances called adipokines, which include adiponectin, leptin, resistin, and hepatocyte growth factor (HGF), etc. Previously, we reported that high levels of plasma HGF at diagnosis indicated intrinsic resistance to EGFR-TKIs. EGFR-TKIs have been hypothesized to affect these adipokines.
  
  
  METHODS
  This prospective study, to evaluate the correlation between plasma adiponectin and insulin levels and non-hematological adverse effects in advanced NSCLC following EGFR-TKIs administration, was conducted at the Osaka City University Hospital. Plasma adiponectin and insulin levels were determined at diagnosis and on treatment day 30.
  
  
  RESULTS
  Overall 33 patients were enrolled. We obtained plasma samples for analyses from all patients at diagnosis and from 26 patients on day 30. Increased adiponectin (13.69 to 14.42 microg/mL, p = 0.0092), and decreased insulin (404.0 to 351.2 pg/mL, p = 0.022) were observed after EGFR-TKI treatments. High levels of adiponectin at diagnosis were associated with severities of skin rash (p = 0.035).
  
  
  CONCLUSIONS
  The adiponectin was affected by EGFR-TKI treatments for NSCLC. Besides, the adverse events by EGFR-TKIs were influenced by the plasma adipokines at diagnosis. Our study may provide useful information regarding patient outcomes to EGFR-TKI treatments. A prospective large clinical trial is warranted to clarify these results.
authors.affiliation: Department of Respiratory Medicine, Osaka City University, Graduate School of Medicine, Japan. m2043009@med.osaka-cu.ac.jp
authors.forename: Kanako
authors.initials: K
authors.lastname: Umekawa
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kimura
authors.forename: Shinzoh
authors.initials: S
authors.lastname: Kudoh
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Suzumura
authors.forename: Misato
authors.initials: M
authors.lastname: Nagata
authors.forename: Shigeki
authors.initials: S
authors.lastname: Mitsuoka
authors.forename: Kuniomi
authors.initials: K
authors.lastname: Matsuura
authors.forename: Takako
authors.initials: T
authors.lastname: Oka
authors.forename: Naruo
authors.initials: N
authors.lastname: Yoshimura
authors.forename: Yukimi
authors.initials: Y
authors.lastname: Kira
authors.forename: Kazuto
authors.initials: K
authors.lastname: Hirata
mesh_terms: D052242:Adiponectin / Q000097:blood*; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000069347:Erlotinib Hydrochloride; D005260:Female; D000077156:Gefitinib; D006801:Humans; D007328:Insulin / Q000097:blood; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000009:adverse effects; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D007328:Insulin; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib