A phase II study of preoperative chemotherapy with docetaxel, cisplatin, and S-1 followed by gastrectomy with D2 plus para-aortic lymph node dissection for gastric cancer with extensive lymph node metastasis: JCOG1002

Abstract

Background Gastric cancer with extensive lymph node metastasis is commonly considered unresectable, with a poor prognosis. We previously reported the results of the use of cisplatin and S-1 as preoperative chemotherapy for gastric cancer with extensive lymph node metastasis; docetaxel, cisplatin, and S-1 (DCS) have now been investigated for the same purpose. Methods Patients received two or three 28-day cycles of DCS therapy (docetaxel at 40 mg/m 2 and cisplatin at 60 mg/m 2 on day 1, S-1 at 40 mg/m 2 twice daily for 2 weeks) followed by gastrectomy with D2 plus para-aortic nodal dissection. After R0 resection, S-1 chemotherapy was given for 1 year. The primary end point was the response rate (RR) to preoperative chemotherapy determined by central peer review according to the Response Evaluation Criteria in Solid Tumors version 1.0. The planned sample size was 50, with one-sided alpha of 10 %, power of 80 %, expected RR of 80 %, and threshold of 65 %. Results Between July 2011 and May 2013, 53 patients were enrolled, of whom 52 were eligible. The clinical RR was 57.7 % [30/52, 80 % confidence interval 47.9-67.1 %, p = 0.89], and R0 resection was achieved in 84.6 % of patients (44/52). Common grade 3 or grade 4 adverse events during DCS therapy were leukocytopenia (18.9 %), neutropenia (39.6 %), and hyponatremia (15.1 %). The common grade 3 or grade 4 surgical morbidity was abdominal infection (10.2 %). The pathological RR was 50.0 % (26/52). Conclusions Preoperative DCS therapy was feasible but did not show a sufficient RR. Preoperative cisplatin and S-1 therapy is still considered the tentative standard treatment for this population until survival results are known.

A phase II study of neoadjuvant chemotherapy with docetaxel, cisplatin, and S-1, followed by gastrectomy with D2 lymph node dissection for high-risk advanced gastric cancer: results of the KDOG1001 trial

“…JCOG1002 was planned as a phase II trial with the expectation that neoadjuvant DCS would be more effective than neoadjuvant CS in terms of tumor shrinkage. This trial evaluated the efficacy of preoperative chemotherapy for not only bulky N2 lymph node metastasis but also para-aortic lymph node metastasis [13]. Contrary to expectation, the primary endpoint, the clinical RR, was 57.7%, which was lower than the predefined threshold rate of 65%.…”

Randomized phase III trial of gastrectomy with or without neoadjuvant S-1 plus cisplatin for type 4 or large type 3 gastric cancer, the short-term safety and surgical results: Japan Clinical Oncology Group Study (JCOG0501)

“…However, docetaxel was not included in the present study. We have previously performed a phase II trial investigating the safety and efficacy of preoperative docetaxel plus CDDP plus S-1 (DCS) in patients with extensive nodal disease [24]. The safety was similar to that of SP regimen.…”

Lymphadenectomy: state of the art

“…As such, in these stages a multidisciplinary approach is advisable, with possible integrated approach including neoadjuvant treatments or intraperitoneal chemotherapy (56). Recent studies reported very good long-term survival rates in patients with extensive or bulky lymph node metastases submitted to neoadjuvant chemotherapy and D2 plus lymphadenectomy (31,57). This is particularly true in Western series, where the rate of diffuse type tumors, associated with a high propensity to spread to regional and distant nodes, is increasing with time (26,56).…”