Feasibility of weekly intraperitoneal versus intravenous paclitaxel therapy delivered from the day of radical surgery for gastric cancer: a preliminary safety analysis of the INPACT study, a randomized controlled trial

Abstract

Background Peritoneal carcinomatosis is common after curative resection of gastric cancer. Intraperitoneal administration of paclitaxel (PTX) is known to control ovarian peritoneal metastases. Patients and methods Patients with either linitis plastica or T4 cancer with high risk of peritoneal metastasis or recurrence but whose cancer was considered resectable were preregistered. After their cancer had been confirmed intraoperatively as resectable, the patients were randomized into either group A (PTX at 60 mg/m 2 intraperitoneally on the day of surgery and on days 14, 21, 28, 42, 49, and 56) or group B (PTX at 80 mg/m 2 administered intravenously by the identical schedule) before being treated by evidence-based chemotherapy. The primary end point was the 2-year survival rate. Safety, the secondary end point, was also analyzed. The study has been registered as UMIN000002957. Results Of 177 preregistered patients, 83 underwent treatment (39 by intraperitoneal administration and 44 by intravenous administration). There was no difference in patient demographics between the two groups. The incidences of surgical complications were similar between the groups, except for transient bowel obstruction observed exclusively in group A. The relative dose intensity of PTX was 81.4 % for group A and 76.3 % for group B. There was one death due to pulmonary thrombosis and a case of anaphylaxis that led to termination of the protocol treatment (group B). Other adverse events were mild and manageable. Conclusions Intraperitoneal administration of PTX from the day of gastrectomy did not result in a higher incidence of surgical complications and adverse reactions when compared with intravenous administration of PTX.

Recent advances in the management of gastric adenocarcinoma patients

“…A subgroup appeared to benefit, but this would only be hypothesis generating 52, 53 . Also, perioperative intraperitoneal chemotherapy is being assessed 54, 55 . The CY-PHOENIX trial showed that intraperitoneal chemotherapy for CY-positive patients (no other site of metastasis) resulted in conversion to CY-negative in 36 patients (94.7%) and 84.2% of the 1-year OS rate 55 .…”

A randomized phase II multicenter trial to explore efficacy of weekly intraperitoneal in comparison with intravenous paclitaxel administered immediately after gastrectomy to the patients with high risk of peritoneal recurrence: final results of the INPACT trial

“…We previously reported on the feasibility and safety of the protocol treatment [13]. In brief, the incidence of surgical complications was similar between the two groups, except for the fact that transient bowel obstruction was observed exclusively in the IP group.…”

“…Before embarking on exploring more complex treatment regimens in combination with other drugs and systemic therapy, we aimed to make a head-to-head comparison of IP vs. IV paclitaxel as a single agent for gastric cancer with high risk of peritoneal disease [12]. IP paclitaxel was found to be safe and feasible in the current multi-institutional randomized phase II trial (INPACT trial), and these results have been published [13]. Here, we report on the final analyses including survival outcomes of the trial.…”

Intraperitoneal chemotherapy for gastric cancer with peritoneal metastasis

“…This trial aimed to provide a theoretical basis for the implementation of intraperitoneal administration of PTX into various combination chemotherapy regimens in future clinical trials. In a preliminary report, Kodera et al stated that the repeated intraperitoneal administration of PTX from the day of gastrectomy was safe and feasible and that the incidence of problems associated with the indwelling catheter for intraperitoneal administration was minimal [65]. The results of an analysis of the two-year recurrence-free survival is expected in 2017.…”

“…Clinical outcomes of intraperitoneal chemotherapy that utilize PTX and DTX for gastric cancer are shown in Tables 1 [52,53,[57][58][59][60][61][62][63][64][65] and 2 [50,[66][67][68][69][70][71][72]. The results of ongoing or recent clinical trials performed by the Japan Intraperitoneal Chemotherapy Study Group (JIPG) to verify the efficacy of intraperitoneal chemotherapy are also shown in Table 3 [73].…”