UNASSIGNED: Low grade serous ovarian carcinoma (LGSOC) is a rare subtype of ovarian cancer (OC) that is challenging to treat due to its relative chemoresistance. Given that LGSOC patients often recur in the peritoneal cavity, novel intraperitoneal (IP) chemotherapy should be explored. Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) is a method that has demonstrated peritoneal disease control in cancers with peritoneal metastases.
UNASSIGNED: NCT04329494 is a US multicenter phase 1 trial evaluating the safety of PIPAC in recurrent ovarian, uterine, and GI cancers with peritoneal metastases. This analysis describes the outcomes of a sub-cohort of four LGSOC patients treated with IP cisplatin 10.5 mg/m2, doxorubicin 2.1 mg/m2 PIPAC q4-6 weeks. Primary endpoints included dose-limiting toxicities (DLT) and incidence of adverse events (AE). Secondary endpoints were progression free survival (PFS) and treatment response based on radiographic, intraoperative, and pathological findings.
UNASSIGNED: Four patients with LGSOC were enrolled of which three were heavily pretreated. Median prior lines of therapy was 5 (range 2-10). Three patients had extraperitoneal metastases, and two patients had baseline partial small bowel obstructive (SBO) symptoms. Median age of patients was 58 (38-68). PIPAC completion rate (≥2 PIPACs) was 75%. No DLTs or Clavien-Dindo surgical complications occurred. No G4/G5 AEs were observed, and one G3 abdominal pain was reported. One patient had a partial response after 3 cycles of PIPAC and completed an additional 3 cycles with compassionate use amendment. Two patients came off study after 2 cycles due to extraperitoneal progressive disease. One patient came off study after 1 cycle due to toxicity. Median decrease in peritoneal carcinomatosis index between cycles 1 and 2 was 5.0%. Ascites decreased in 2 out of 3 patients who had ≥2 PIPACs. Median PFS was 4.3 months (1.7-21.6), median overall survival was 11.6 months (5.4-30.1), and objective response rate was 25%.
UNASSIGNED: PIPAC with cisplatin/doxorubicin is well tolerated in LGSOC patients without baseline SBO symptoms. IP response was seen in 2 out of 3 patients that completed ≥2 PIPAC cycles. Further study of PIPAC for patients with recurrent disease limited to the IP cavity and with no partial SBO symptoms should be considered.

OBJECTIVE: Despite advances in systemic therapy, outcomes of patients with gastric cancer (GC) peritoneal carcinomatosis (PC) remain poor, in part because of poor penetrance of systemic therapy into peritoneal metastasis due to the plasma-peritoneal barrier and anarchic intra-tumoral circulation. Hence, regional treatment approach with administration of chemotherapy directly into the peritoneal cavity (intraperitoneal, IP) under various conditions, combined with or without cytoreductive surgery (CRS) has remained an area of significant research interest. The purpose of this review is to provide high-level evidence for regional treatment approaches in the management of GCPC with limited peritoneal disease.
METHODS: A review of the current literature and ongoing clinical trials for regional IP therapies for GCPC was performed. Studies included in this review comprise of phase III randomized controlled trials, non-randomized phase II studies, high-impact retrospective studies, and active ongoing clinical trials for each available IP modality.
RESULTS: The three common IP approaches are heated intraperitoneal chemotherapy (HIPEC), normothermic intraperitoneal chemotherapy (NIPEC) and more recently introduced, pressurized intraperitoneal aerosolized chemotherapy (PIPAC). These IP approaches have been combined with systemic therapy and/or CRS with varying degrees of promising results, demonstrating evidence of improvements in survival rates and peritoneal disease control. Patient selection, optimization of systemic therapy, and completeness of cytoreduction have emerged as major factors influencing the design of contemporary and ongoing trials.
CONCLUSIONS: IP chemotherapy has a clear role in the management of patients with GCPC, and when combined with CRS in appropriately selected patients has the potential to significantly improve survival. Ongoing and upcoming IP therapy clinical trials hold great promise to shape the treatment paradigm for GCPC.