Pressurized intraperitoneal aerosol chemotherapy with low-dose cisplatin and doxorubicin (PIPAC C/D) in patients with gastric cancer and peritoneal metastasis: a phase II study

Abstract

Background: Efficacy of second-line systemic chemotherapy in recurrent gastric cancer with peritoneal metastasis (RGCPM) is limited. We assessed the feasibility, safety and possible efficacy of pressurized intraperitoneal aerosol chemotherapy (PIPAC) in patients with RGCPM after ⩾1 line of palliative intravenous chemotherapy. Methods: In this open-label, single-arm, monocentric phase II ICH-GCP clinical trial, patients were scheduled for three courses of PIPAC with cisplatin 7.5 mg/m 2 and doxorubicin 1.5 mg/m 2 (PIPAC C/D) every 6 weeks. Patients with bowel obstruction or extraperitoneal metastasis were ineligible. The primary endpoint was clinical benefit rate (CBR) by Response Evaluation Criteria in Solid Tumors based on clinical records. Secondary endpoints included overall survival (OS), median time to progression (TTP), peritoneal carcinomatosis index (PCI), histological regression and ascites volume. Safety and tolerability were assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4, quality of life (QoL) by EORTC-QLQ30 questionnaire. Results: A total of 25 patients were enrolled and available for the analysis of the primary endpoint. Of those 25 patients, 10 (40%) had a radiological complete, partial response or stable disease. Median OS [intention to treat (ITT)] was 6.7 months, median TTP was 2.7 months. Complete or major regression on histology were observed in 9/25 patients (36%, ITT) or 6/6 [100%, per protocol (PP)] patients. There were no suspected unexpected serious adverse reactions, no treatment-related deaths, no CTCAE grade 4 toxicity and three (12%) grade 3 toxicities. Changes in the QLQ-C30 scores during PIPAC C/D therapy were small and not significant. Conclusions: PIPAC C/D was well tolerated and active in patients with RGCPM. Survival was encouraging. Randomized controlled trials should now be designed in this indication.

Multimodality Treatment in Metastatic Gastric Cancer: From Past to Next Future

“…Recently, the most significant development in intraperitoneal-directed therapy is pressurized intraperitoneal aerosol chemotherapy (PIPAC), a minimally invasive procedure, generally safe and well tolerated, capable of achieving a more uniform distribution and deeper peritoneal penetration in gaseous state when compared to liquid chemotherapy [ 94 ]. Data on efficacy and safety of PIPAC in GC patients with peritoneal metastases remains limited, with only 4 studies (2 retrospective studies and 2 phase II trials), comprising a total of 274 PIPAC procedures administered in 119 GC patients [ 94 , 95 , 96 , 97 ]. In these studies, mOS rates, major complication rates, and mortality rates ranged between 4.0–19.5 months, 0–29% and 0–8.3%, respectively [ 94 , 95 , 96 , 97 ].…”

“…Data on efficacy and safety of PIPAC in GC patients with peritoneal metastases remains limited, with only 4 studies (2 retrospective studies and 2 phase II trials), comprising a total of 274 PIPAC procedures administered in 119 GC patients [ 94 , 95 , 96 , 97 ]. In these studies, mOS rates, major complication rates, and mortality rates ranged between 4.0–19.5 months, 0–29% and 0–8.3%, respectively [ 94 , 95 , 96 , 97 ]. The multicenter, international online documentation of indications and results of PIPAC (PIPACRegis—NCT03210298), is an international prospective patient registry intended to collect clinical data from 1000 cancer patients undergoing PIPEC.…”

Overcoming Drug Resistance by Taking Advantage of Physical Principles: Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC)

“…All three components are now part of PIPAC [57]. Starting with the first preclinical experiments through technology development, first in-human use [58], Phase 1 [59][60][61] and Phase 2 [62][63][64][65][66][67] trials, PIPAC is currently being evaluated in randomized controlled trials [68][69][70][71][72] for palliative therapy of PM [73]. PIPAC ( Figure 3) is applied through laparoscopic access using two balloon trocars in an operating room equipped with laminar air flow.…”

Peritoneal metastatic gastric carcinoma cells exhibit more malignant behavior when co-cultured with HMrSV5 cells

“…The metastasis of gastric cancer cells to the peritoneum usually proceeds along peri-gastric regions to the branches of the celiac trunk [7]. Surgery and chemotherapy can somewhat alleviate the pain caused by the peritoneal metastasis of gastric cancer [8]. However, the five-year relapse-free survival rate for peritoneal metastatic gastric cancer patients is only 53% [6].…”