Bidirectional Neoadjuvant Chemotherapy for Patients with Gastric Cancer and Synchronous Peritoneal Metastases (GCPMs): Results of a Western Phase II Study

胃癌合并同步性腹膜转移(GCPMs)患者的双向新辅助化疗:一项西方II期研究的结果

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Abstract

Background: The outcomes of patients with peritoneal metastases from gastric cancer (GCPMs) remain dismal, with an overall survival (OS) of less than 1 year. Approaches reported from East Asia include normothermic intraperitoneal systemic chemotherapy, aimed at downstaging the disease, allowing an R0 resection. This is the first Western study evaluating a bidirectional regimen in a neoadjuvant setting of GCPMs. This phase II study evaluates the tolerability, efficacy and conversion surgery rate. Methods: Patients with PCI < 13 without ascites or HER2 overexpression and no extraperitoneal spread were enrolled starting in January 2018. After staging laparoscopy combined with PIPAC (cisplatin + doxorubicin), NIPS began following Yonemura's schedule: cisplatin (30 mg/m(2)) + docetaxel (30 mg/m(2)), intraperitoneally (day 1); capecitabine 1000 mg/m(2), orally (days 2-15); and cisplatin (30 mg/m(2)) + docetaxel (30 mg/m(2)), intravenous (day 8). After three cycles, patients with no progressive disease and negative peritoneal cytology underwent cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Three additional NIPS cycles were reserved for patients who underwent surgery. Results: Among the 25 treated patients with 17.3-month (95%CI: 10.4; NA) OS, no adverse events (CTCAE) ≥ G3 arose. With a 52% conversion surgery rate, 13 patients underwent CRS combined with HIPEC (cisplatin 100 mg/m(2)), 10 with CC0 status 3 with CC experienced no operative mortality, and major complications rated Clavien-Dindo IIIB occurred in 2 patients (15.4%). The median OS for patients undergoing surgery was 26 (95%CI: 23.1; NA) months, with progression-free survival of 20 (95%CI: 16.7-NA) months. Conclusions: NIPS is safe and effective. The conversion rate in our Western patients is comparable to that reported in Eastern Asian countries.

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