Treatment of PERItoneal disease in Stomach Cancer with cytOreductive surgery and hyperthermic intraPEritoneal chemotherapy: PERISCOPE I initial results

Abstract

Background The role of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in gastric cancer is unknown. This non‐randomized dose‐finding phase I–II study was designed to assess the safety and feasibility of HIPEC, following systemic chemotherapy, in patients with gastric cancer and limited peritoneal dissemination. The maximum tolerated dose of normothermic intraperitoneal docetaxel in combination with a fixed dose of intraperitoneal oxaliplatin was also explored. Methods Patients with resectable cT3–cT4a gastric adenocarcinoma with limited peritoneal metastases and/or tumour‐positive peritoneal cytology were included. An open HIPEC technique was used with 460 mg/m2 hyperthermic oxaliplatin for 30 min followed by normothermic docetaxel for 90 min in escalating doses (0, 50, 75 mg/m2). Results Between 2014 and 2017, 37 patients were included. Of 25 patients who completed the full study protocol, four were treated at dose level 1 (0 mg/m2 docetaxel), six at dose level 2 (50 mg/m2) and four at dose level 3 (75 mg/m2). At dose level 3, two dose‐limiting toxicities occurred, both associated with postoperative ileus. Thereafter, another 11 patients were treated at dose level 2, with no more dose‐limiting toxicities. Based on this, the maximum tolerated dose was 50 mg/m2 intraperitoneal docetaxel. Serious adverse events were scored in 17 of 25 patients. The reoperation rate was 16 per cent (4 of 25) and the treatment‐related mortality rate was 8 per cent (2 patients, both in dose level 3). Conclusion Gastrectomy combined with cytoreductive surgery and HIPEC was feasible using 460 mg/m2 oxaliplatin and 50 mg/m2 normothermic docetaxel.

Risk Factors for Metachronous Isolated Peritoneal Metastasis after Preoperative Chemotherapy and Potentially Curative Gastric Cancer Resection: Results from the CRITICS Trial

“…Hypothesizing that, specifically, patients with limited peritoneal disease seem to benefit from HIPEC, prophylactic HIPEC treatment has been suggested to potentially prevent or postpone peritoneal metastasis [ 16 , 17 ]. However, HIPEC is associated with considerable morbidity [ 18 ] and, preferably, should be restricted to a select group of patients with a very high risk for developing isolated PM. An accurate prediction model to identify these patients at high risk for metachronous isolated PM that might benefit from prophylactic treatment is, therefore, needed.…”

A Prospective, Phase I/II, Open-Label Pilot Trial to Assess the Safety of Hyperthermic Intraperitoneal Chemotherapy After Oncological Resection of Pancreatic Adenocarcinoma

“… 25 Recent work comparable with our study, performed in peritoneal metastasis from gastric cancer, has shown substantial treatment-related mortality, with 50% mortality at the highest investigated dose level of docetaxel in combination with oxaliplatin. 26 Furthermore, serious adverse events were reported in 17/25 patients.…”

“…An immanent design aspect of this clinical trial is that no control group without HIPEC treatment has been included, which does limit the precise attribution of adverse events to specific parts of the investigated treatment. Furthermore, the heterogeneous patient cohort and surgical treatment may raise legitimate critique in the context of oncological benefits, whereas these circumstances do not interfere with the primary endpoints of this trial (see also van der Kaaij et al 26 ).…”

Hyperthermic Intraperitoneal Chemotherapy: A Critical Review

“…The initial results of the PERISCOPE-trial aimed at dosefinding were recently published. Although the amount of serious adverse events in the trial was high (17 out of 25 patients), it was shown that HIPEC with a dose of 50 mg/m 2 intraperitoneal docetaxel appeared to be feasible [100] Survival data from that trial are currently awaited.…”