title: Plasma RANTES, IL-10, and IL-8 levels in non-small-cell lung cancer patients treated with EGFR-TKIs.
abstract: BACKGROUND
  Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), routinely used to treat advanced non-small-cell lung cancer (NSCLC) patients with activated EGFR mutations, are associated with excellent response and improved performance status. Recently, pro-inflammatory cytokines, such as regulated upon activation normal T cell expressed and secreted (RANTES), interleukin (IL)-10 and IL-8 have been proposed as mediators of cancer development. EGFR-TKIs have been found to affect this network of pro-inflammatory cytokines.
  
  
  METHODS
  EGFR-TKIs (erlotinib, 150 mg/day; and gefitinib, 250 mg/day) were administered once per day. Treatment was continued until disease progressed or the patient developed intolerable symptoms of toxicity, or withdrew his/her consent for study participation. The treatment was a part of standard care. We investigated the correlation between plasma pro-inflammatory cytokines (including plasma RANTES, IL-10, and IL-8) levels and clinical outcomes following EGFR-TKI treatment in lung cancer patients. Pro-inflammatory cytokine levels were evaluated at diagnosis and on treatment day 30 after the first administration of EGFR-TKIs.
  
  
  RESULTS
  Overall, 33 patients were enrolled. Plasma pro-inflammatory cytokine levels were determined for all patients at diagnosis. Plasma samples from 26 patients were obtained on treatment day 30. High level of RANTES at diagnosis was associated with severe general fatigue (P = .026). Low level of RANTES at diagnosis was significantly associated with long-term survival (P = .0032). Percent decrease change of IL-10 was associated with severity of rash (P = .037). The plasma IL-8 level on treatment day 30 (median, 5.48 pg/mL; range, 0.49-26.13 pg/mL) was significantly lower than the level at diagnosis (median 10.45 pg/mL; 3.04-54.86 pg/mL; P = .021).
  
  
  CONCLUSIONS
  These results suggest that EGFR-TKIs may suppress systemic inflammation and promote tumor shrinkage. The network of pro-inflammatory cytokines was affected by EGFR-TKI treatment for NSCLC. In addition, the clinical outcomes of EGFR-TKI treatment were influenced by the status of the plasma pro-inflammatory cytokines at diagnosis.
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
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: Takako
authors.initials: T
authors.lastname: Oka
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: Toshiyuki
authors.initials: T
authors.lastname: Nakai
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: D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy; D018946:Chemokine CCL5 / Q000097:blood*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D000069347:Erlotinib Hydrochloride; D005260:Female; D000077156:Gefitinib; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007249:Inflammation; D016753:Interleukin-10 / Q000097:blood*; D016209:Interleukin-8 / Q000097:blood*; D008175:Lung Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011799:Quinazolines / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D018946:Chemokine CCL5; D016209:Interleukin-8; D011799:Quinazolines; D016753:Interleukin-10; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D000077156:Gefitinib