Karina Dahl Steffensen1, Christine Vestergaard Madsen2, Rikke Fredslund Andersen3, Marianne Waldstrøm4, Parvin Adimi5, Anders Jakobsen6. 1. Department of Oncology, Vejle Hospital, Kabbeltoft 25, DK-7100 Vejle, Denmark; Institute of Regional Health Research, University of Southern Denmark, Winsløwparken 19,3, DK-5000 Odense C, Denmark. Electronic address: Karina.Dahl.Steffensen@rsyd.dk. 2. Department of Oncology, Vejle Hospital, Kabbeltoft 25, DK-7100 Vejle, Denmark; Institute of Regional Health Research, University of Southern Denmark, Winsløwparken 19,3, DK-5000 Odense C, Denmark. Electronic address: Christine.Vestergaard.Madsen@rsyd.dk. 3. Department of Clinical Biochemistry, Vejle Hospital, Kabbeltoft 25, DK-7100 Vejle, Denmark. Electronic address: Rikke.Fredslund.Andersen@rsyd.dk. 4. Department of Pathology, Vejle Hospital, Kabbeltoft 25, DK-7100 Vejle, Denmark. Electronic address: Marianne.Waldstroem@rsyd.dk. 5. Department of Oncology, Vejle Hospital, Kabbeltoft 25, DK-7100 Vejle, Denmark. Electronic address: Parvin.Adimi@rsyd.dk. 6. Department of Oncology, Vejle Hospital, Kabbeltoft 25, DK-7100 Vejle, Denmark; Institute of Regional Health Research, University of Southern Denmark, Winsløwparken 19,3, DK-5000 Odense C, Denmark. Electronic address: Anders.Jakobsen@rsyd.dk.
Abstract
AIM: Treatment of multiresistant epithelial ovarian cancer (EOC) is palliative and patients who have become resistant after multiple lines of chemotherapy often have an unmet need for further and less toxic treatment. Anti-angiogenic therapy has attracted considerable attention in the treatment of EOC in combination with chemotherapy. However, only a minor subgroup will benefit from the treatment and there is an obvious need for new markers to select such patients. The purpose of this study was to investigate the effect of single-agent bevacizumab in multiresistant EOC and the importance of circulating cell-free DNA (cfDNA) in predicting treatment response. METHODS: One hundred and forty-four patients with multi-resistant EOC were treated with single-agent bevacizumab 10mg/kg every three weeks. Baseline plasma samples were analysed for levels of cfDNA by real-time polymerase chain reaction (PCR). RESULTS: Eighteen percent responded to treatment according to CA125 and 5.6% had partial response by Response Evaluation Criteria in Solid Tumours (RECIST). Stable disease was seen in 53.5% and 48.6% of the patients by CA125 and RECIST, respectively. Median progression free survival (PFS) and overall survival (OS) were 4.2 and 6.7 months, respectively. Cell-free DNA was highly correlated to PFS (p=0.0004) and OS (p=0.005) in both univariate and multivariate analyses (PFS, hazard ratio (HR)=1.98, p=0.002; OS, HR=1.66, p=0.02), as patients with high cfDNA had a poor outcome. CONCLUSIONS: Single-agent bevacizumab treatment in multiresistant EOC appears to be a valuable treatment option with acceptable side-effects. Cell-free DNA showed independent prognostic importance in patients treated with bevacizumab and could be applied as an adjunct for treatment selection.
AIM: Treatment of multiresistant epithelial ovarian cancer (EOC) is palliative and patients who have become resistant after multiple lines of chemotherapy often have an unmet need for further and less toxic treatment. Anti-angiogenic therapy has attracted considerable attention in the treatment of EOC in combination with chemotherapy. However, only a minor subgroup will benefit from the treatment and there is an obvious need for new markers to select such patients. The purpose of this study was to investigate the effect of single-agent bevacizumab in multiresistant EOC and the importance of circulating cell-free DNA (cfDNA) in predicting treatment response. METHODS: One hundred and forty-four patients with multi-resistant EOC were treated with single-agent bevacizumab 10mg/kg every three weeks. Baseline plasma samples were analysed for levels of cfDNA by real-time polymerase chain reaction (PCR). RESULTS: Eighteen percent responded to treatment according to CA125 and 5.6% had partial response by Response Evaluation Criteria in Solid Tumours (RECIST). Stable disease was seen in 53.5% and 48.6% of the patients by CA125 and RECIST, respectively. Median progression free survival (PFS) and overall survival (OS) were 4.2 and 6.7 months, respectively. Cell-free DNA was highly correlated to PFS (p=0.0004) and OS (p=0.005) in both univariate and multivariate analyses (PFS, hazard ratio (HR)=1.98, p=0.002; OS, HR=1.66, p=0.02), as patients with high cfDNA had a poor outcome. CONCLUSIONS: Single-agent bevacizumab treatment in multiresistant EOC appears to be a valuable treatment option with acceptable side-effects. Cell-free DNA showed independent prognostic importance in patients treated with bevacizumab and could be applied as an adjunct for treatment selection.
Authors: Katarina Kalavska; Tomas Minarik; Barbora Vlkova; Denisa Manasova; Michaela Kubickova; Andrej Jurik; Jozef Mardiak; Jozef Sufliarsky; Peter Celec; Michal Mego Journal: J Ovarian Res Date: 2018-09-22 Impact factor: 4.234