Phase II Study of Preoperative Intra-Arterial Epirubicin, Etoposide, and Oxaliplatin Combined with Oral S-1 Chemotherapy for the Treatment of Borrmann Type 4 Gastric Cancer

Abstract

Purpose: A phase II study was conducted to evaluate the safety and efficacy of preoperative, intra-arterial perfusion of epirubicin, etoposide, and oxaliplatin combined with oral chemotherapy S-1 (SEEOX) for the treatment of type 4 gastric cancer.

Materials and methods: A single-center, single-arm phase II trial was conducted on 36 patients with histologically proven type 4 gastric cancer without distant peritoneal or organ metastasis. Patients received 3, 21-day courses of SEEOX preoperative chemotherapy. The primary endpoint was overall survival (OS) and the secondary outcomes assessed were chemotherapeutic response, radical resection rate, pathological regression, toxicities, postoperative morbidity, and mortality.

Results: All patients were at an advanced stage of cancer (stage III or IV) and completed the entire course of treatment. Based on changes in tumor volume and peritoneal metastasis, the objective response rate was 55.6% (20/36; 95% confidence interval [CI], 38.5%-72.6%) and the disease control rate was 69.4% (25/36; 95% CI, 53.6%-85.3%). The radical resection rate was 75% (27/36; 95% CI, 60.1%-89.9%) and the proportion of R0 resections was 66.7% (21/36; 95% CI, 50.5%-82.8%). The pathological response rate was 33.3%, of which 13.9% showed complete pathological regression. The median survival was 27.1 months (95% CI, 22.24-31.97 months), and the 2-year OS was 48.5% (95% CI, 30.86%-66.1%).

Conclusions: Preoperative SEEOX is a safe and effective treatment for type 4 gastric cancer. Based on these preliminary data, a phase III study will be conducted to confirm the superiority of this regimen over standard treatment.

Trial registration: ClinicalTrials.gov Identifier: NCT02949258.

Keywords: Gastric cancer; Linitis plastica; Neoadjuvant chemotherapy.

Conflict of interest statement

Conflict of Interest: No potential conflict of interest relevant to this article was reported.

Copyright © 2020. Korean Gastric Cancer Association.

Figures

Fig. 1. The CONSORT flow chart.

Fig. 2. Waterfall plot of tumor volume changes and typical CT graphs. (A) Waterfall plot showing changes in tumor volume, peritoneal metastasis and peritoneal lavage cytology. Patients 1–3 did not undergo laparoscopy due to disease progression, and patient 4 due to the large amount of ascites. (B) Typical CT images of patients who received SEEOX preoperative chemotherapy. Patient A is a 71-year-old surviving male diagnosed with P0CY1. After preoperative treatment, CT evaluation indicated CR, re-laparoscopy revealed P0CY0 and histological examination showed complete pathological regression. Patient B was a 45-year-old male diagnosed with P0CY1. CT evaluation and re-laparoscopy respectively indicated PR (−90%) and P0CY0. The histological subtype of this tumor was signet ring cell carcinoma, T4aN2M0, TRG3. The patient passed away 17 months post-surgery due to peritoneal metastasis. Patient C is a surviving 67-year-old male diagnosed with P1CY0. CT evaluation showed PR (−60%), re-laparoscopy indicated P0CY0 and the histological subtype indicated poorly differentiated adenocarcinoma, T4bN3M0, TRG3. Patient D is a surviving 65-year-old female diagnosed with P0CY1. CT evaluation showed PR (−30%), re-laparoscopy revealed P0CY0 and a complete pathological regression was seen.

CT = computed tomography; SEEOX = S-1, etoposide, oxaliplatin and epirubicin; CR = complete response; PR = partial response.

Fig. 3. (A) Kaplan-Meier OS curve of 36 enrolled patients. (B) Kaplan-Meier OS curves of resected (n=27) and unresected (n=9) patients (P

OS = overall survival.