Objective      To investigate the correlation of serum levels of cytokines with clinical outcomes of erlotinib in the second- or third-line therapies to treat the patients with advanced non-small cell lung cancer (NSCLC).       Methods      One hundred and sixty-two patients with advanced NSCLC who received erlotinib as either second- or third-line treatment in our department from January 2007 to May 2011 were enrolled in this study. Their median age was 58 years. In this group

109 were male

and 53 were female. Seventy-four were former or current smokers

and 88 were non-smokers. One hundred and twenty-two patients presented with adenocarcinoma

27 had squamous cell carcinoma

and 13 had tumors with other types of histology. Blood samples were collected before the initiation of erlotinib

and the serum levels of IL-1β

IL-2R

IL-6 and TNF-α were assessed by enzyme-linked immunosorbent assay (ELISA). Cutoff points were defined as the median levels to divided the patients into low and high level groups (IL-1β

26.5 pg/ml; IL-2R

115 pmol/L; IL-6

49.5 pg/ml; TNF-α

48.5 pg/ml). Kaplan-Meier analysis was performed to estimate the survival time

and Cox regression analyses were employed to correlate cytokines and baseline clinical characteristics with clinical outcomes

including time to progression (TTP) and overall survival (OS).       Results      One hundred and thirty-nine patients had an eastern cooperative oncology group (ECOG) performance status of 0 to 1

while the left 23 scored at 2 to 3. Serum levels of IL-1β

IL-2R and IL-6 were not significantly associated with age

gender

ECOG performance status

smoking status

histology

or stage of tumor. But that of TNF-α was associated with smoking status (P=0.045). Survival analysis showed that patients with low levels of IL-6 had a statistically longer TTP and OS than patients with high expression (P0.01)

whereas the subgroup of patients with low levels of TNF-α also demonstrated statistically better TTP and OS than the high level group (P0.01). Cox regression multivariate analysis indicated that these 2 cytokines were both independent factors related to survival (P0.01).       Conclusion      For advanced NSCLC patients with erlotinib as second- or third-line treatments

those have low levels of IL-6 or TNF-α show a longer TTP and OS than those with high levels

indicating that these 2 cytokines might be served as predictive biomarkers for the efficacy of erlotinib.