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

Giorgi Nadiradze, Urs Giger-Pabst, Juergen Zieren, Dirk Strumberg, Wiebke Solass, Marc-André Reymond, Giorgi Nadiradze, Urs Giger-Pabst, Juergen Zieren, Dirk Strumberg, Wiebke Solass, Marc-André Reymond

Abstract

Background: Pressurized 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.

Methods: Retrospective 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/m(2) and doxorubicin 1.5 mg/m(2) 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.

Results: Median 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.

Conclusion: PIPAC 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.

Keywords: Cisplatin; Doxorubicin; Gastric cancer; Intraperitoneal chemotherapy; Peritoneal metastasis; Pressurized intraperitoneal aerosol chemotherapy.

Figures

Fig. 1
Fig. 1
PIPAC is well tolerated. Although the dose applied is only 10 % of a usual systemic dose, patients develop a postoperative inflammatory syndrome with elevated C-reactive protein, probably explained by a chemical peritonitis. However, acute and cumulative local toxicities of PIPAC are well controlled and no bowel perforation and no gastrointestinal side effects > CTCAE grade 2 were observed
Fig. 2
Fig. 2
Fifty-one years old female patient after R1 gastrectomy, postoperative chemotherapy (FLOT), and radiochemotherapy (5-FU) for GC, intestinal type, pT3 pN2 pM1 (per). Videolaparoscopy (a1) and CT scan (a2) at PIPAC#1 showing multiple small bowel involvement (white arrows) and radiological diffuse small bowel thickening (red arrows). At PIPAC # 4, videolaparoscopy shows a complete macroscopic response (b1) and CT a complete radiological response according to RECIST 1.1 criteria (b2). Number sign: micropump placed into the abdomen during laparoscopy. Asterisk: local peritonectomy scar. Multiple biopsies confirm major remission with extensive fibrosis and isolated vital tumor cells. Patient was alive 148 days after 1st PIPAC with a KI of 90 %
Fig. 3
Fig. 3
Kaplan-Meier survival curve of 24 consecutive patients after PIPAC salvage therapy with cisplatin and doxorubicin. x-axis: survival in months; y-axis: cumulative survival. Green line: patients with peritoneal carcinomatosis (PC) plus other metastases. Blue line: patients with PC without other metastases

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