Plasma levels of IL-8 and g-CSF in high-grade gliomas treated with bevacizumab.

Abstract

2083 Background: Bevacizumab, an anti-VEGF antibody, has shown significant activity in high grade gliomas (HGG). However, tumor recurrence inevitably occurs. Methods: We treated 63 recurrent HGG patients with poor prognostic factors with bevacizumab (10 mg/kg) and irinotecan (125 or 340 mg/m2) every 2 weeks, and investigated IL-12, IL-13, IL-17, FGF basic, G-CSF, MIP-1b, PDGF-beta, plasma levels before starting treatment and every 8 weeks by Bioplex. Ten age- and sex-matched healthy controls were used for comparison. Results: After a median follow-up of 27 weeks, median OS and PFS were 33 and 18 weeks, respectively. PFS at 6 and 12 months were 32% and 12%, respectively. OS at 6 months was 60%. Toxicity was mild. Baseline higher amounts of IL-13 (48±174 pg/ml vs 3.44±0.9 pg/ml, p=0.0001) and lower amounts of MIP-1b (35.3±20.9 pg/ml vs 67.2±18.8 pg/ml, p=0.0002), PDGF-beta (1585.5±1585 pg/ml vs 7098±1585 pg/ml, p=0.0001) and VEGF (27±39.8 pg/ml vs 54.5±32 pg/ml, p=0.001) were detected in patients than in healthy controls. In a cohort of 15 non-responders (patients who progressed 8 weeks after treatment onset), baseline IL-8 (15.7±10.8 pg/ml vs 10.9±9.4 pg/ml, p=0.03) and G-CSF (113.3±54 pg/ml vs 84.9±59.2 pg/ml, p=0.03) were significantly higher than in patients responding to treatment. In the same cohort no significant reduction of VEGF and other cytokines was observed after 8 weeks of treatment, while a decrease of plasma VEGF was observed in the remaining patients (26±32 pg/ml vs 13.3±28.5 pg/ml, p=0.001). Furthermore, in a cohort of 22 long-term responders (patients who progressed after more than 18 weeks of treatment), levels of VEGF decreased after 8 weeks of treatment when compared to baseline, whereas no difference was observed in baseline levels (23.9±22.6 pg/ml vs 9.8±9.4 pg/ml, p=0.001). Conclusions: Data suggest that high levels of IL-8 and G-CSF at baseline associated with a lack of VEGF decrease after 8 weeks of treatment identify patients who are resistant to bevacizumab. This hypothesis should be tested in a large number of patients.