A Phase III Randomized Clinical Trial: The Impact of Paclitaxel-Based Neoadjuvant Laparoscopic Hyperthermic Intraperitoneal Chemotherapy (NLHIPEC) Followed by Sequential Intravenous Chemotherapy in Advanced High-Grade Serous Ovarian Cancer Patients - Interim Analysis of Safety and Immediate Efficacy from the C-HOC Trial

Objective This study evaluates the potential superiority of combining paclitaxel-based neoadjuvant laparoscopic hyperthermic intraperitoneal chemotherapy (NLHIPEC) with sequential intravenous neoadjuvant chemotherapy over intravenous neoadjuvant chemotherapy (IV NACT) alone in Chinese patients with Federation of Gynecology and Obstetrics (FIGO) stage IIIC-IVB high-grade serous ovarian/fallopian tube carcinoma (HGSOC). This interim analysis focuses on the safety and immediate efficacy of both regimens to determine the feasibility of a planned phase III trial. Methods In a single-center, open-label, phase III trial, FIGO stage IIIC-IVB HGSOC patients (FAGOTTI score ≥8 during laparoscopic exploration) unsuitable for optimal cytoreduction in primary debulking surgery (PDS) were randomized 2:1 during laparoscopic exploration. The NLHIPEC group received one cycle of intraperitoneal neoadjuvant laparoscopic hyperthermic intraperitoneal chemotherapy (paclitaxel) followed by three cycles of intravenous chemotherapy (paclitaxel plus carboplatin), while the IV NACT group received only three cycles of intravenous chemotherapy. Both groups subsequently underwent interval debulking surgery (IDS). This partial analysis focuses on comparing adverse effects of chemotherapy, postoperative complications, and pathological chemotherapy response scores (CRS) after IDS. Results Among 65 enrolled patients, 39 NLHIPEC and 21 IV NACT patients underwent IDS. Grade 3-4 chemotherapy-related adverse effects were primarily hematological with no significant differences between two groups. The NLHIPEC group exhibited a higher proportion of CRS 3 (20.5% vs. 4.8%; P=0.000). R0 resection rates in IDS were 69.2% (NLHIPEC) and 66.7% (IV NACT). R2 resection occurred in 2.6% (NLHIPEC) and 14.3% (IV NACT) cases. No reoperations or postoperative deaths were reported, and complications were managed conservatively. Conclusions Combining NLHIPEC with IV NACT in treating ovarian cancer demonstrated safety and feasibility, with no increased chemotherapy-related adverse effects or postoperative complications. NLHIPEC improved tumor response to neoadjuvant chemotherapy, potentially enhancing progression-free survival (PFS). However, the final overall survival results are pending, determining if NLHIPEC combined with IV NACT is superior to IV NACT alone Keyword: high-grade serous ovarian/fallopian tubecarcinoma (HGSOC); paclitaxel; neoadjuvant chemotherapy;hyperthermic intraperitoneal chemotherapy (HIPEC); chemotherapy response score (CRS). ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial Chinese Clinical Trial Registry platform (ChiCTR2000028894) ### Funding Statement This study did not receive any funding. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study received approval from the Ethics Committee of Ruijin Hospital I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Datasets utilized and analyzed during this study are available from the corresponding author upon reasonable request.