OBJECTIVES: A nonrandomized trial was planned to investigate the role of free plasma DNA (FPDNA) in patients with epithelial ovarian cancer before and after chemotherapy. Twenty-two patients with advanced stage ovarian cancer not suitable for debulking were treated with a neoadjuvant platinum/taxanes chemotherapy. Patients with clinical complete or partial response underwent radical hystero-oophorectomy, omentectomy, and lymphadenectomy and were followed up every 3 to 6 months. METHODS: Blood samples were obtained from each patient before chemotherapy, before each cycle, before and after surgery. FPDNA was quantified by real-time quantitative polymerase chain reaction using the Quantifiler Human Quantification Kit and expressed in ng/mL. Fifty female healthy blood donor volunteers were used as controls. RESULTS: Median FPDNA quantities discriminated between patients before chemotherapy (29.6+/-22.7 ng/mL) and controls (6.4+/-4.0 ng/mL) using a 14.5 ng/mL cutoff with 77% sensitivity and 96% specificity (P<0.001). Mean FPDNA concentrations significantly decreased after chemotherapy (17.9+/-14.5 ng/mL, P=0.001). A peak of FPDNA levels (66.2+/-45.2 ng/mL) was observed in association with surgery (P<0.001). Median follow-up and median progression-free survival time were 13.4+/-5.1 and 11.7+/-5.6 months, respectively. Eight patients with FPDNA values above the cutoff after chemotherapy showed disease progression or died, whereas 7 patients with FPDNA below the cutoff were free from disease. Patients with FPDNA levels above and below the cutoff showed significantly separated progression-free survival curves (P=0.007, log-rank test). CONCLUSIONS: FPDNA quantification significantly discriminates between cancer patients and controls and correlates with response to chemotherapy. Although performed in a limited series, we demonstrated a correlation between FPDNA values and clinical behavior of ovarian cancer patients.