Effect of neoadjuvant chemotherapy combined with intraperitoneal chemotherapy after interval tumor cell reduction on the prognosis of advanced epithelial ovarian cancer

Objectives: To investigate the effect of neoadjuvant chemotherapy combined with intraperitoneal chemotherapy after interval tumor cell reduction on the prognosis of advanced epithelial ovarian cancer. Methods: A retrospective study was performed among 210 patients with advanced ovarian cancer who were treated with neoadjuvant chemotherapy from May 1, 2007 to December 1, 2015. 121 patients with NACT-IDS (Neoadjuvant chemotherapy followed by interval debulking surgery) were enrolled. The patients were divided into observation group (NACT-IDS + IP group, n = 28) and control group (NACT-IDS + IV group, n = 93) depending on whether intraperitoneal chemotherapy was used after interval debulking surgery. The effects of intraperitoneal chemotherapy after NACT-IDS on PFS (progression-free survival) and OS (overall survival) were analyzed and the influencing factors were explored through multivariate analysis. The competitive model was used to analyze the effect of intraperitoneal chemotherapy after NACT-IDS on tumor recurrence. Toxicities associated with adjuvant chemotherapy were also analyzed between two groups. The effect of neoadjuvant chemotherapy cycles on prognosis and the correlation between postoperative CA125 decline and recurrence were evaluated. Results: Intraperitonal chemotherapy and R0 (no gross residual) were independent factors for PFS, with HRs of 0.560 (95% CI, 0.342–0.918, p = 0.022) and 0.578 (95% CI, 0.377–0.887, p = 0.012). There was no independent factor associated with OS. Significant difference in PFS was detected among the R0 + IP group, R0 + IV group, non-R0 + IP group and non-R0 + IV group. In patients with R0 tumor reduction, IP patients showed significantly better PFS, bonferronei adjusted p = 0.036. In patients without R0 tumor reduction, no significant difference was detected between IP and IV group, bonferronei adjusted p = 0.28. There were no significant differences of grade 3–4 toxicities, abdominal pain, treatment delays, dose reductions, and treatment modifications in NACT-IDS + IP group and NACT-IDS + IV group. Neoadjuvant chemotherapy cycles ($\le$3 and $>$3) were not the influencing factors of PFS or OS and did not affect platinum-sensitive relapse or platinum-resistant relapse. The decrease in postoperative CA125 was not related to platinum-sensitive recurrence or platinum-resistant recurrence. Conclusions: Neoadjuvant chemotherapy combined with intraperitoneal chemotherapy after interval debulking surgery could improve the PFS of patients with advanced epithelial ovarian cancer compared to intravenous chemotherapy without significant differences in toxicity.

Interval debulking surgery; Neoadjuvant chemotherapy; Intraperitoneal chemotherapy; Ovarian neoplasms

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