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.