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

Florian Struller, Philipp Horvath, Wiebke Solass, Frank-Jürgen Weinreich, Dirk Strumberg, Marios K Kokkalis, Imma Fischer, Christoph Meisner, Alfred Königsrainer, Marc A Reymond, Florian Struller, Philipp Horvath, Wiebke Solass, Frank-Jürgen Weinreich, Dirk Strumberg, Marios K Kokkalis, Imma Fischer, Christoph Meisner, Alfred Königsrainer, Marc A Reymond

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/m2 and doxorubicin 1.5 mg/m2 (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.

Keywords: Cisplatin; doxorubicin; gastric cancer; histological regression; intraperitoneal chemotherapy; objective tumor response; peritoneal metastasis; pressurized intraperitoneal aerosol chemotherapy (PIPAC).

Conflict of interest statement

Conflict of interest statement: Marc André Reymond is a holder of patents related to PIPAC C/D technology and a shareholder of Capnomed GmbH, Zimmern, Germany. The other authors have no potential conflict of interests.

Figures

Figure 1.
Figure 1.
Study flowchart. CT, computed tomography; CRS, cytoreductive surgery; HIPEC, hyperthermic intraperitoneal chemotherapy; PIPAC, pressurized intraperitoneal aerosol chemotherapy.
Figure 2.
Figure 2.
Example of a complete radiological response according to RECIST version 1.1 in a patient with RGCPM after three cycles of PIPAC C/D. (a1/b1) PIPAC cycle 1: arrows highlight the thickening of the parietal peritoneal layer due to PM; star shows intraabdominal ascites. (a2/b2) PIPAC cycle 2: arrows mark the decreasing thickening of the parietal peritoneal layer; the ascites disappeared. (a3/b3) PIPAC cycle 3: arrows highlight the parietal peritoneal layer without any radiological signs of PM; no intraabdominal ascites can be seen. Patient was alive 31 months after PIPAC cycle 1. C/D, cisplatin and doxorubicin; PIPAC, pressurized intraperitoneal aerosol chemotherapy; PM, peritoneal metastasis; RECIST, Response Evaluation Criteria in Solid Tumors; RGCPM, recurrent gastric cancer with peritoneal metastasis.
Figure 3.
Figure 3.
Overall survival of 25 patients with RGCPM treated with PIPAC C/D in the salvage situation. Median survival was 6.7 months (95% CI: 2.5–12.0). x-axis, follow up (months since first PIPAC); y-axis, cumulative survival (Kaplan–Meier). CI, confidence interval; PIPAC C/D, pressurized intraperitoneal aerosol chemotherapy with cisplatin and doxorubicin; RGCPM, recurrent gastric cancer with peritoneal metastasis.

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