Plasma RANTES, IL-10, and IL-8 levels in non–small-cell lung cancer patients treated with EGFR-TKIs

BMC Research Notes

Kazuto Hirata²  Yukimi Kira¹  Naruo Yoshimura²  Toshiyuki Nakai²  Kuniomi Matsuura²  Shigeki Mitsuoka²  Misato Nagata²  Takako Oka²  Tomohiro Suzumura²  Shinzoh Kudoh²  Tatsuo Kimura²  Kanako Umekawa² 

[1] Department of Central Laboratory, Graduate School of Medicine, Osaka City University, Osaka, Japan;Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan

关键词: IL-10;    IL-8;    RANTES;    EGFR-TKIs;    NSCLC;   

Others  :  1142965
DOI  :  10.1186/1756-0500-6-139

 received in 2012-11-26, accepted in 2013-03-28,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Umekawa et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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