Impact of antibiotic treatment during platinum chemotherapy on survival and recurrence in women with advanced epithelial ovarian cancer.

ABSTRACT

OBJECTIVE(S) To determine whether antibiotic treatment (ABX) during platinum chemotherapy (PC) for epithelial ovarian cancer (EOC) impacts progression-free survival (PFS) and overall survival (OS). STUDY DESIGN: Retrospective single institution cohort study in women with newly diagnosed stage III/IV EOC (n = 424) who underwent cytoreductive surgery (CRS) and PC from 2009 to 2015. ABX for >48 h, including ABX against gram-positive (anti-G + ABX) bacteria were recorded. The impact of ABX on PFS and OS was assessed using univariate and multivariable Cox regression models. RESULTS: Of 424 eligible women, 34.7% (n = 147) received ABX, with 11.3% (n = 48) treated with anti-G + ABX. ABX decreased PFS (17.4 vs. 23.1 months, HR 1.50, 95% CI 1.20-1.88, p < 0.001) and OS (45.6 vs. 62.4 months, HR 1.63, 95% CI 1.27-2.08, p < 0.001) compared to no ABX. Similarly, anti-G + ABX worsened PFS (16.5 vs. 23.1 months; HR 1.85, 95% CI 1.33-2.55) and OS (35.0 vs. 62.4 months; HR 2.12, 95% CI 1.50-3.0, p < 0.001). On multivariable analysis, all ABX and anti-G + ABX significantly worsened PFS (HR 1.31, 95% CI 1.04-1.65, p = 0.02), (HR 1.50, 95% CI 1.07-2.10, p = 0.02) and OS (HR 1.52, 95% CI 1.18-1.96, p = 0.001), (HR 1.83, 95% CI 1.27-2.62, p = 0.001) respectively. Increased Clavien Dindo score was associated with worsened PFS (1-2 - HR 1.52, 95% CI 1.14-2.03, p = 0.004; 3-4 - HR 1.86, 95% CI 1.27-2.72, p = 0.001) but not OS (1/2 - HR 1.35, 95% CI 0.97-1.88, p = 0.08; 3/4 - HR 1.53, 95% CI 1.00-2.34, p = 0.05); residual disease (p < 0.05) and neoadjuvant chemotherapy (p < 0.001) were associated with worse PFS and OS. CONCLUSION(S) In this retrospective cohort study of women with advanced EOC undergoing PC, ABX treatment was associated with decreased PFS and OS. Mechanistic studies are needed to investigate the negative impact of ABX upon PC response in EOC.