Cisplatin and paclitaxel are associated with improved progression-free survival compared to cisplatin alone during interval debulking surgery with hyperthermic intraperitoneal chemotherapy in women with advanced epithelial ovarian cancer

Abstract

<h3>Objectives:</h3> To investigate progression-free survival (PFS) and peri-operative outcomes in women with EOC undergoing interval debulking surgery (IDS) with hyperthermic intraperitoneal chemotherapy (HIPEC) with paclitaxel/cisplatin (PC) vs single-agent cisplatin (C). <h3>Methods:</h3> This study was an Institutional Review Board approved, a single-institution cohort study of women with stage III or IV high-grade EOC treated from 1/1/2017-3/1/2020, followed in a prospective HIPEC registry with at least six months of follow-up. HIPEC regimen was administered at primary surgeon's discretion: C alone (80-100mg/m² for 90 minutes) or P (135-175mg/m² for 90 minutes) with C (80-100mg/m² for 45 minutes) in a perfusate of normal saline at 41-43C degrees for 90 minutes, as previously described.3 PFS was defined as months from HIPEC date to recurrence. A Log-rank test was performed for PFS between PC vs. C. A p-value of < 0.05 was considered statistically significant. <h3>Results:</h3> In total, 54 eligible patients underwent IDS with HIPEC following 3-4 cycles of NACT with carboplatin and paclitaxel were identified from a prospectively maintained HIPEC registry. Patients underwent HIPEC with C (51.9%, n=28) or PC (n=26; 48.1%). All patients underwent optimal cytoreduction to less than 1cm of residual disease. There were no differences in patient demographics, including age (67.4 vs 63.3 years, p=0.10), race (p=0.99), medical co-morbidities (p > 0.05), and pre-operative American Society of Anesthesiologists (ASA) score (III or IV - 64.3% vs 80.8%, p=0.18) for those who received C vs. PC. Additionally, the majority of patients had stage III disease (77.8% vs 76.9%, p=0.87) and serous histology (100.0% vs 92.3%, p=0.23). There were no differences in operative time (6.0 hours vs 5.3 hours, p=0.11) or surgical procedures performed, including small bowel (3.6% vs 3.8%, p=0.99) and large bowel resection (17.9% vs 23.1%, p=0.63). Notably, no differences in the Accordion postoperative adverse events were appreciated (None – 42.9% vs 42.3%; Mild – 25.0% vs 38.5%; Moderate – 21.4% vs 7.7%; Severe – 7.1% vs 11.5%; Death – 3.6% vs 0.0%; p=0.46). Additionally, there was no difference in need for blood transfusion (50.0% vs 57.7%, p=0.57), intra-operative vasopressor use (75.0% vs 92.3%, p=0.14) or ICU admission (7.1% vs 26.9%, p=0.07) The median PFS for the entire cohort was 15.7 months. However, when stratified by treatment regimen, PFS was 10.9 vs 22.2 months for C vs PC, respectively (HR 0.38, 95% CI 0.18, 0.81, p=0.009) (Figure). <h3>Conclusions:</h3> In this analysis of a prospective HIPEC registry, we demonstrate that PC is associated with a significantly improved PFS compared to C, without increased postoperative morbidity in patients with optimally cytoreduced stage III/IV EOC undergoing IDS with HIPEC. While further study is ongoing regarding overall survival benefit, consideration should be given for incorporation of P with C at the time of IDS with HIPEC.