Phase III randomized controlled trial of hypotonic intraperitoneal cisplatin combined with oral UFT/PSK for the adjuvant treatment of gastric cancer invading the serosa

Abstract

4027 Background: Peritoneal seeding is the most common pattern of recurrence in patients with gastric cancer invading the serosa who underwent curative gastrectomy. We developed hypotonic intraperitoneal cisplatin for preventing peritoneal recurrence in experimental models. Hypotonic cisplatin had a significant tumorcidal effect in vitro and in vivo. Hypotonic intraperitoneal cisplatin was tolerable in phase I clinical study. Now, we investigated the efficacy of the treatment in a multicenter prospective randomized controlled trial. Methods: 134 pts treated with curative resection for gastric cancer invading the serosa were randomized during surgery to one of 2 treatment arms. As per protocol, eligibility was confirmed by pathology and treatment course in 108 pts as follows: A -Hypotonic intraperitoneal cisplatin (100mg/m2) during surgery and systemic UFT (300mg/day) + PSK (protein-bound polysaccharide, 3g/day) (n=54) and B-Systemic UFT + PSK (n=48). Cisplatin diluted in 1,000 ml of warmed distilled water was injected to the abdominal cavity before closure of the abdomen. Drains were closed for 1 hour after injection of cisplatin. Results: Median follow up was 6.8 years. Postoperative complication rate and side effects were 21.3% and 30.8% in A-arm and 22.4% and 24.0% in B-arm. Tolerance was good in both arms. Peritoneal recurrence rate was 26.9% in A-arm and 40.0% in B-arm (chi-square p=0.16). Overall survival at 5 years was 62.0% and 31.0% in pts with or without hypotonic intraperitoneal cisplatin (log-rank p=0.03). Conclusions: Combining hypotonic intraperitoneal cisplatin and systemic oral chemotherapy improves the efficacy of oral chemotherapy after curative surgery for gastric cancer invading the serosa. No significant financial relationships to disclose.