Safety and efficacy of bidirectional chemotherapy for treatment of patients with peritoneal dissemination from gastric cancer: Selection for cytoreductive surgery

Abstract

There is no standard treatment for peritoneal carcinomatosis (PC) from gastric cancer. New bidirectional chemotherapy (neoadjuvant intraperitoneal-systemic chemotherapy protocol (NIPS)) was developed. The aim of the present study was to assess the safety and efficacy of NIPS and to show the selection for cytoreductive surgery on PC from gastric cancer. Seventy-nine patients with PC from gastric cancer were treated with NIPS. A peritoneal port system was introduced into the abdominal cavity. The peritoneal wash cytological examination through a port was done before and after NIPS. The patients were treated with oral TS-1 twice a daily for 21 days, followed by a 1-week rest. On day 1, 8, and 15 from the start of oral TS-1 administration, 30 mg/m 2 of Docetaxel and 30 mg/m 2 of cisplatinum with 500 ml of saline were introduced into the peritoneal cavity through the port. A median course of oral TS-1 was 2.1 course and a median time of IP chemoterapy was 5.8. Peritoneal free cancer cells (PFCCs) had been detected in 65 (82.2%) patients before NIPS, and the positive cytology changed to be negative in 41 (63.0%) patients after NIPS. After NIPS, 41 patients underwent laparotomy, and complete cytoreduction was done in 32 (78%) patients. Complete cytoreduction was done in 27 (51.9%) of 52 patients with negative cytology but in only 4 (14.8%) of 27 patients with positive cytology (P < 0.001). Patients with negative cytology after NIPS survived significantly longer than those with positive cytology. The adverse effects after NIPS were mild and there was no treatment-related deaths. The grade 3/4 hematological adverse effects were found in 2 (2.6%) patients. Grade 3 renal toxicity and port site infection was found in three patients, respectively. NIPS using a port system is a safe and effective treatment for PC. Peritoneal wash cytology through a port system is a good indicator to select the patients to perform cytoreductive surgery.

Hyperthermic intraperitoneal perfusion chemotherapy and response evaluation in patients with gastric cancer and malignant ascites

“…PC has been estimated to be responsible for 60% of all gastric cancer-associated mortalities, with peritoneal metastases in these patients considered terminal (6,20,21). Therapy consists mainly of palliative chemotherapy; long-term survival is considered poor, since systemic chemotherapy agents are unlikely to reach cytotoxic concentrations in peritoneal nodules (22)(23)(24)(25)(26)(27).…”

A critical analysis of the cytoreductive surgery with hyperthermic intraperitoneal chemotherapy combo in the clinical management of advanced gastric cancer: an effective multimodality approach with scope for improvement

“…The combined application of hyperthermia and chemotherapy has a significant synergistic effect (17)(18)(19)(20)(21). Hyperthermia can eliminate and inhibit the ability of some oncogenes in the target cells to control cellular uptake and drug excretion, hence decreasing drug excretion while increasing the cumulative drug concentration.…”

The Role of Hyperthermic Intraperitoneal Chemotherapy in Gastric Cancer

“…Details of this technique have been published elsewhere [65]. In short, after inserting a peritoneal port system into the abdominal cavity, oral S-1 is administered for 21 days at a dose of 60 mg/m2.…”

“…The response to neoadjuvant chemotherapy is another independent prognostic factor. After a NIPS protocol, a negative cytology has been shown to be associated with a better survival than a positive cytology (3 year survival 8.5 % vs 0 %) [65], and a major (grade 2/3) response has a better outcome than a lesser (HR = 2.6, 95 % CI = 1.17-3.98, p = 0.002) [66]. The other factors that have been found to predict a better survival after CRS & HIPEC include synchronous PM [57,60], systemic chemotherapy >6 cycles and no serious adverse events [60] and absence of signet ring cell histology [69] and absence of ascites [57].…”