Abstract：
BACKGROUND: In gastric cancer, peritoneal metastasis is the most common form of metastasis and leads to dismal prognosis. We aimed to evaluate the safety and efficacy of combining perioperative intraperitoneal (IP) plus systemic chemotherapy, cytoreductive surgery (CRS), and hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with gastric cancer with limited peritoneal metastasis or even after reducing peritoneal tumor burden by upfront IP chemotherapy.
METHODS: Patients were enrolled in phase Ib in a 3 + 3 dose escalation of IP paclitaxel plus a fixed dose of IP cisplatin and oral S-1. In phase II, patients were managed according to the peritoneal cancer index (PCI) by diagnostic laparoscopy. For patients with a PCI of >12, upfront IP and systemic chemotherapy were given. Patients with a PCI of ≤12 or reduced to ≤12 after upfront chemotherapy underwent CRS with HIPEC. The primary endpoints were safety and the recommended phase II dose (RP2D) confirmation for phase Ib and the 1-year overall survival rate for phase II.
RESULTS: The RP2D was defined as IP 175 mg/m2 paclitaxel and 60 mg/m2 cisplatin and oral 70 mg/m2/day S-1 for 14 days. A total of 22 patients were included. After CRS with HIPEC, there were no grade 3 or higher complications. The median hospital stay was 7 days (range, 6-11). The median overall and progression-free survival were 27.3 months (95% CI, 14.4 to not estimable) and 12.6 months (95% CI, 7.7-14.5), respectively. One-year overall and progression-free survival rates were 81.0% (95% CI, 65.8-99.6) and 54.5% (95% CI, 37.2-79.9), respectively.
CONCLUSIONS: A combination of IP plus systemic chemotherapy, CRS, and HIPEC was safe and resulted in good survival outcomes.
METHODS: Patients were enrolled in phase Ib in a 3 + 3 dose escalation of IP paclitaxel plus a fixed dose of IP cisplatin and oral S-1. In phase II, patients were managed according to the peritoneal cancer index (PCI) by diagnostic laparoscopy. For patients with a PCI of >12, upfront IP and systemic chemotherapy were given. Patients with a PCI of ≤12 or reduced to ≤12 after upfront chemotherapy underwent CRS with HIPEC. The primary endpoints were safety and the recommended phase II dose (RP2D) confirmation for phase Ib and the 1-year overall survival rate for phase II.
RESULTS: The RP2D was defined as IP 175 mg/m2 paclitaxel and 60 mg/m2 cisplatin and oral 70 mg/m2/day S-1 for 14 days. A total of 22 patients were included. After CRS with HIPEC, there were no grade 3 or higher complications. The median hospital stay was 7 days (range, 6-11). The median overall and progression-free survival were 27.3 months (95% CI, 14.4 to not estimable) and 12.6 months (95% CI, 7.7-14.5), respectively. One-year overall and progression-free survival rates were 81.0% (95% CI, 65.8-99.6) and 54.5% (95% CI, 37.2-79.9), respectively.
CONCLUSIONS: A combination of IP plus systemic chemotherapy, CRS, and HIPEC was safe and resulted in good survival outcomes.
摘要：
背景：在胃癌中，腹膜转移是最常见的转移形式，并导致预后不良。我们旨在评估围手术期腹膜内（IP）联合全身化疗的安全性和有效性，细胞减灭术（CRS），和腹腔热化疗（HIPEC）的胃癌患者腹膜转移，甚至在通过预先IP化疗减轻腹膜肿瘤负担之后。
方法：Ib期患者接受3+3剂量递增的IP紫杉醇加固定剂量的IP顺铂和口服S-1。在第二阶段,根据腹膜癌指数(PCI)通过诊断性腹腔镜检查对患者进行治疗.对于PCI>12的患者，给予预先IP和全身化疗。PCI≤12或在前期化疗后降低至≤12的患者接受HIPECCRS。主要终点是安全性和Ib期的推荐II期剂量（RP2D）确认以及II期的一年总生存率。
结果：RP2D定义为IP175mg/m2紫杉醇和60mg/m2顺铂，口服70mg/m2/天S-1，持续14天。共纳入22例患者。在使用HIPEC的CRS之后，无3级或更高的并发症.中位住院时间为7天(范围，6-11).中位总生存期和无进展生存期为27.3个月(95%置信区间[CI]，14.4-不可估计)和12.6个月(95%CI，7.7-14.5)，分别。一年总生存率和无进展生存率分别为81.0%（95%CI，65.8-99.6）和54.5%（95%CI，37.2-79.9），分别。
结论：IP联合全身化疗，CRS,和HIPEC是安全的，并导致良好的生存结局。
方法：Ib期患者接受3+3剂量递增的IP紫杉醇加固定剂量的IP顺铂和口服S-1。在第二阶段,根据腹膜癌指数(PCI)通过诊断性腹腔镜检查对患者进行治疗.对于PCI>12的患者，给予预先IP和全身化疗。PCI≤12或在前期化疗后降低至≤12的患者接受HIPECCRS。主要终点是安全性和Ib期的推荐II期剂量（RP2D）确认以及II期的一年总生存率。
结果：RP2D定义为IP175mg/m2紫杉醇和60mg/m2顺铂，口服70mg/m2/天S-1，持续14天。共纳入22例患者。在使用HIPEC的CRS之后，无3级或更高的并发症.中位住院时间为7天(范围，6-11).中位总生存期和无进展生存期为27.3个月(95%置信区间[CI]，14.4-不可估计)和12.6个月(95%CI，7.7-14.5)，分别。一年总生存率和无进展生存率分别为81.0%（95%CI，65.8-99.6）和54.5%（95%CI，37.2-79.9），分别。
结论：IP联合全身化疗，CRS,和HIPEC是安全的，并导致良好的生存结局。
