Concentrations of cisplatin and doxorubicin in ascites and peritoneal tumor nodules before and after pressurized intraperitoneal aerosol chemotherapy (PIPAC) in patients with peritoneal metastasis

Abstract

Introduction: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new means of delivering chemotherapy into the abdomen of patients with peritoneal carcinomatosis (PC). The amount of drug uptake in ascites and peritoneum after PIPAC is unknown.

Methods: Retrospective cohort study of women with PC from gynecological tumors comparing the concentrations of cisplatin and doxorubicin in ascites and peritoneum before and after PIPAC. Concentrations were measured using gas chromatography. Peritoneal tumor samples were assessed for histological tumor regression.

Results: 59 PIPAC procedures were performed in 32 women with PC. The concentrations of doxorubicin and cisplatin in ascites significantly increased after PIPAC (140.2 ± 671.5 vs 9035.7 ± 5328.6 ng/ml; p < 0.0001 and 95.2 ± 106.4 vs 24,770.8 ± 11,710.8 ng/ml; p < 0.0001, respectively). Concentrations of doxorubicin and cisplatin in peritoneal tissue also significantly increased after PIPAC (5.1 ± 0.7 vs 19.2 ± 38.6 ng/g; p = 0.007, and 81.9 ± 7.8 vs 131.5 ± 134.4 ng/g; p = 0.005, respectively). On an individual patient level, a significant uptake (>2-fold) of doxorubicin and cisplatin was observed in 57/59 (97%) and 58/59 (98%) of cases in ascites and in 23/59 (39%) and 13/59 (22%) of cases in the peritoneum. Uptake of cisplatin and doxorubicin were significantly correlated (Spearman correlation coefficient: 0.33; p = 0.011). After repeated PIPACs, doxorubicin uptake increased in peritoneal tumor tissue (p = 0.008).

Conclusions: PIPAC leads to a significant chemotherapy uptake in both ascites and peritoneum, suggesting a bimodal cytotoxic effect of PIPAC via direct tissue uptake into peritoneal tumor nodules and via ascites. Consecutive PIPAC applications lead to peritoneal accumulation of doxorubicin, suggesting a cumulative cytotoxic effect of doxorubicin after repeated PIPACs.

Keywords: Ascites; Drug uptake; High pressure; Intraabdominal chemotherapy; Peritoneal carcinomatosis; Toxicity.