Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) with Low-Dose Cisplatin and Doxorubicin in Gastric Peritoneal Metastasis

Abstract

BackgroundPressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel technique of intraperitoneal chemotherapy. First results obtained with PIPAC in patients with advanced peritoneal metastasis (PM) from gastric cancer (GC) are presented.MethodsRetrospective analysis: Sixty PIPAC were applied in 24 consecutive patients with PM from GC. 67 % patients had previous surgery, and 79 % previous platinum-based systemic chemotherapy. Mean Peritoneal Carcinomatosis Index (PCI) of 16 ± 10 and 18/24 patients had signet-ring GC. Cisplatin 7.5 mg/m2 and doxorubicin 1.5 mg/m2 were given for 30 min at 37 °C and 12 mmHg at 6 week intervals. Outcome criteria were survival, adverse events, and histological tumor response.ResultsMedian follow-up was 248 days (range 105–748), and median survival time was 15.4 months. Seventeen patients had repeated PIPAC, and objective tumor response was observed in 12 (12/24 = 50 %): no vital tumor cells = 6, major pathological response = 6, minor response = 3. Postoperative adverse events > CTCAE 2 were observed in 9 patients (9/24, 37.5 %). In 3/17 patients, a later PIPAC could not be performed due to non-access. Two patients (ECOG 3 and 4) died in the hospital due to disease progression.ConclusionPIPAC with low-dose cisplatin and doxorubicin was safe and induced objective tumor regression in selected patients with PM from recurrent, platinum-resistant GC. First survival data are encouraging and justify further clinical studies in this indication.Electronic supplementary materialThe online version of this article (doi:10.1007/s11605-015-2995-9) contains supplementary material, which is available to authorized users.

Functional vascular anatomy of the peritoneum in health and disease

“…Our own experience shows that exposition of the peritoneum to cisplatin and doxorubicin during induces a major systemic inflammatory response that must be caused by the chemical peritonitis, since no other actions are taken [69]. There are other isolated reports on intraabdominal inflammatory reaction following intraperitoneal chemotherapy [70].…”

Nanomedicine-based intraperitoneal therapy for the treatment of peritoneal carcinomatosis — Mission possible?

“…Experimental and clinical studies show that PIPAC has promising antitumor activity in ovarian, gastric, and colorectal carcinomatosis [36,37]. Prospective studies (NCT02604784, NCT02320448, NCT01854255), investigating the efficacy of PIPAC in recurrent gastric cancer are currently recruiting patients.…”

Electrostatic precipitation Pressurized IntraPeritoneal Aerosol Chemotherapy (ePIPAC): first in-human application

“…Since the therapeutic ratio between local and systemic drug concentration is increased by PIPAC, enhanced local efficacy together with low systemic toxicity was expected and has been confirmed clinically [9]. Retrospective analysis of first patient cohorts in ovarian [10], gastric [11] and colorectal [12] cancer have shown encouraging results of PIPAC in the palliative situation, with relatively high efficacy and favorable safety profiles. A first prospective phase-2 trial with low-dose doxorubicin and cisplatin in recurrent, platinum-resistant ovarian cancer applied as PIPAC has confirmed these results with a clinical benefit rate (CBR) of 62% and an objective histological regression rate of 76%, coupled with a low incidence of severe adverse events (15% CTCAE grade 3, no CTCAE grade 4 and 5) [13].…”