ABSTRACT
OBJECTIVES: This randomized phase II trial investigated the efficacy and safety of docetaxel plus bevacizumab and S-1 plus bevacizumab in the second-line treatment of non-squamous (non-Sq) non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Patients with non-Sq NSCLC who experienced disease progression after prior platinum-based chemotherapy with or without bevacizumab were randomly assigned to receive docetaxel plus bevacizumab (DB) once every 3 weeks or S-1 orally twice daily on days 1-14 plus bevacizumab (SB) on day 1 every 3 weeks until disease progression. RESULTS: Ninety patients were randomized. The median progression-free survival (PFS) was 3.9 months (95% confidence interval [CI]=3.0-6.5) in DB and 3.5 months (95% CI=2.9-5.9) in SB. The objective response rate was significantly higher in DB than in SB (22.2% vs. 2.2%; P=0.004), whereas the disease control rates of the arms were identical (62.2% vs. 62.2%; P=1.00). Patients receiving DB were more likely to have ≥grade 3 neutropenia (93.4% vs. 4.4%) and febrile neutropenia (33.3% vs. 0%) than SB. In DB, PFS and overall survival (OS) were significantly longer among bevacizumab-naïve patients than among bevacizumab-experienced patients (median PFS: 7.2 vs. 2.9 months; P=0.004; and median OS: 21.3 vs. 14.1 months; P=0.012). CONCLUSION: DB and SB produced modest PFS benefits in the second-line treatment of patients with advanced non-Sq NSCLC. Because of the toxicity of DB and the low response rate of SB, neither regimen warrants further investigation, excluding DB in bevacizumab-naïve patients with advanced non-Sq NSCLC.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bevacizumab/administration & dosage , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Docetaxel , Drug Combinations , Female , Humans , Kaplan-Meier Estimate , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Oxonic Acid/administration & dosage , Platinum/administration & dosage , Retreatment , Taxoids/administration & dosage , Tegafur/administration & dosage , Treatment OutcomeABSTRACT
Interferon gamma (IFN-gamma) production is a critical step of antituberculosis (anti-TB) immune response. The purpose of this study was to determine the influences of biologics, including the interleukin (IL)-6 receptor-inhibitor tocilizumab (TCZ), and tumor necrosis factor (TNF) antagonists infliximab (INF) and etanercept (ETA), on Mycobacterium tuberculosis (MTB) antigen-induced IFN-gamma production. MTB antigen (ESAT-6 and CFP-10)-induced IFN-gamma-releasing assay was performed with or without addition of biologics (TCZ, ETA, and INF) using whole blood from patients with active TB. ETA and INF inhibited IFN-gamma production in a dose-dependent manner. In whole blood from TB patients, ESAT-6 stimulated significant production of IFN-gamma (1.30 +/- 1.95 IU/ml), and TCZ did not inhibit IFN-gamma production (1.56 +/- 1.88 IU/ml). IFN-gamma production by ESAT-6 was inhibited by ETA and INF (0.98 +/- 1.74, 0.75 +/- 1.66 IU/ml, respectively). CFP-10 stimulated significant production of IFN-gamma (1.46 +/- 1.60 IU/ml), and TCZ did not inhibit IFN-gamma production (1.51 +/- 1.77 IU/ml). IFN-gamma production by CFP-10 was inhibited by ETA and INF (0.91 +/- 0.99, 0.72 +/- 0.88 IU/ml, respectively). TCD did not inhibit MTB antigen-induced IFN-gamma production. As IFN-gamma production is important in antimycobacterial host defenses, the minimal influence of TCZ on IFN-gamma-releasing assay suggests a low risk of latent TB infection reactivation during tocilizumab therapy.
