Continuous hyperthermic peritoneal perfusion for the prevention of peritoneal recurrence of gastric cancer: Randomized controlled study

Abstract

We performed continuous hyperthermic peritoneal perfusion (CHPP) or continuous normothermic peritoneal perfusion (CNPP) combined with cisplatin (CDDP) 300 mg/kg and mitomycin C (MMC) 30 mg/kg in an attempt to prevent peritoneal recurrence after surgery for gastric cancer. Twenty-two patients were treated with perfusion using about 10 liters of saline heated to 41 degrees to 42 degrees C (CNPP group); 18 patients were treated with saline heated to 37 degrees to 38 degrees C (CNPP group); and 18 patients underwent only gastric surgery without perfusion (control group) in a randomized control study. There were two deaths (9%) due to peritoneal recurrence in the CHPP group, four (22%) in the CNPP group, and four (22%) in the control group. The 1-, 2-, and 3-year survival rates were 95%, 89%, and 68%, in the CHPP group; 81%, 75%, and 51%, in the CNPP group; and 43%, 23%, and 23%, in the control group, respectively. There was a significant difference between the three survival curves by the log-rank test (p < 0.01). This difference showed that CNPP and CHPP are both effective procedures for preventing peritoneal recurrence. The maximum concentrations in the perfusate of total and free CDDP with 300 mg administration were 12.2 and 10.1 micrograms/ml, respectively, at the end of the perfusion, and the maximum concentrations of total and free CDDP in plasma were 2.1 and 1.0 micrograms/ml, respectively. The maximum concentrations of MMC in perfusate and plasma with 30 mg administration were 1.00 and 0.05 micrograms/ml, respectively, which are intraperitoneally cytotoxic but systemically safe concentrations.

Pharmacokinetic and Pharmacodynamic Analysis of Hyperthermic Intraperitoneal Oxaliplatin-Induced Neutropenia in Subjects with Peritoneal Carcinomatosis

“…Peritoneal fluid and venous blood samples were collected immediately after the oxaliplatin administration and then every 10 min until the end of the peritoneal perfusion. Additional venous blood samples were drawn at 0.25, 0.5, 1, 1.5, 2, 2.5, 3,4,6,8,12,16,20,24, and 28 h after the end of the peritoneal perfusion. All samples were collected in S-monovette® tubes, centrifuged at 3,500 rpm for 10 min and were stored at −80°C until analysis.…”

“…However, there are no PC treatment approved by regulatory agencies, and the development of new therapies to manage this life-threatening condition could fulfill an unmet medical need. In this context, several Phase I/II clinical studies in gastric cancer (1)(2)(3), mesothelioma (4), colorectal (5), or ovarian carcinoma (6) have shown promising results in treating macroscopic PC with cytoreductive surgery and residual PC with hyperthermic intraperitoneal chemotherapy (HIPEC) (7). The rationale for this treatment is based on experimental studies showing that drug penetration is limited to a few cell layers under the surface of the tumor (8), and consequently, intraperitoneal chemotherapy must be immediately administered after the cytoreductive surgery in order to achieve the maximal cytotoxic activity on residual tumor cells before they get trapped in the postoperative fibrin adhesions (9).…”

Survival outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis from gastric cancer: a systematic review

“…Since then, various Asian groups have gone on to investigate the use of HIPEC in the prophylactic setting [21,25,26,[83][84][85][86][87]. All of them have provided evidence to show that HIPEC in the prophylactic setting can reduce the incidence of peritoneal recurrence and improve survival.…”

Intraperitoneal Chemotherapy as a Multimodal Treatment for Gastric Cancer Patients with Peritoneal Metastasis

“…IPC with MMC or carbon-adsorbed MMC has been reported to improve survival of gastric cancer patients by preventing peritoneal recurrence [4,5], but the efficacy of these therapies was not confirmed by the Austrian Gastric Cancer Working Group [59]. Fujimura et al [14] have showed that patients treated with intraoperative HIPEC with cisplatin, MMC and etoposide had longer survival than the control group, but this result was not confirmed by Kunisaki et al [60]. These discrepant data seem to be influenced by the number of free cancer cells disseminated during surgical treatment.…”

“…The efficacy of IPC seems to be affected mainly by the extent of the peritoneal tumor and ascites. Most of positive results were obtained for patients without peritoneal metastasis in an adjuvant setting or for patients with microscopic residual tumor [13][14][15][16][17][18][19][20][21][22].…”