Indoleamine 2,3-dioxygenase activity and clinical outcome following induction chemotherapy and concurrent chemoradiation in stage III non-small cell lung cancer.

Abstract

10538 Background: Indoleamine 2,3-dioxygenase (IDO) has recently been proposed as an inducible promoter of tumor-related immunosuppression through the metabolism of tryptophan into kynurenine. Our objective was to prospectively correlate IDO activity with response type and survival in non-small cell lung cancer (NSCLC) patients treated with combined modality therapy. Methods: This is a companion study to a single-arm phase II trial of first-line induction gemcitabine and carboplatin followed by concurrent paclitaxel and carboplatin with 74 Gy thoracic radiation in stage III NSCLC. Serum kynurenine and tryptophan levels were drawn at baseline, post-induction, and post-concurrent treatment. Imaging studies were repeated 8 weeks after therapy. Kynurenine to tryptophan ratio (kyn/trp) was used as a surrogate for IDO activity. Kyn/trp was tested by analysis of variance and log-rank for relationships to clinical outcomes. Results: Characteristics of 28 participants: 13 females; median age 62. Median overall survival (OS) was 18.8 months (mo), and median progression-free survival (PFS) was 11.5 mo. Mean kyn/trp at baseline (4.25) increased after induction (5.04, p = 0.09) and chemoradiation (6.11, p = 0.04). Association of post-treatment increase in kyn/trp with radiologic response type was not statistically significant (p = 0.21). No significant correlation was found between post-chemoradiation kyn/trp and PFS (HR 0.97, 95% CI 0.84 - 1.12, p=0.68) or OS (HR 0.96, 95% CI 0.83 - 1.10, p = 0.51). Post-induction chemotherapy increase in kyn/trp was significantly related to worse OS (HR 1.25, 95% CI 1.01 - 1.56, p= 0.04). Conclusions: In this exploratory study, kyn/trp ratio increased during chemoradiation for NSCLC, possibly due to therapy-related inflammation inducing IDO activity within tumors. Increased IDO activity following chemotherapy may be a means for tumors to maintain immune suppression, and NSCLC may be a potential area for the application of IDO inhibitors.