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

doi:10.1177/1758835919846402

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

Ther Adv Med Oncol. 2019 May 13:11:1758835919846402. doi: 10.1177/1758835919846402. eCollection 2019.

Affiliations

¹ Department of General and Transplant Surgery, Tübingen, University Hospital, Hoppe-Seyler-Strasse 3, 72076 Tübingen, Germany.
² Department of General and Transplant Surgery, University Hospital Tübingen, Germany.
³ Department of Pathology, University Hospital Tübingen, Germany.
⁴ Department of Medical Oncology, Marien Hospital, Ruhr University Bochum, Germany.
⁵ Institute for Clinical Epidemiology and Applied Biometrics, University Hospital Tübingen, Germany.
⁶ Department of General and Transplant Surgery, University Hospital Tübingen, Germany National Center for Pleura and Peritoneum, University Hospital, Tübingen, Germany.

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).