Short-term outcomes of preoperative chemotherapy with docetaxel, oxaliplatin, and S-1 for gastric cancer with extensive lymph node metastasis (JCOG1704)

Abstract

Background The prognosis for marginally resectable gastric cancer with extensive lymph node metastasis (ELM) remains unfavorable, even after R0 resection. To assess the safety and efficacy of preoperative docetaxel, oxaliplatin, and S-1 (DOS), we conducted a multicenter phase II trial. Methods Eligibility criteria included histologically proven HER2-negative gastric adenocarcinoma with bulky nodal (bulky N) involvement around major branched arteries or para-aortic node (PAN) metastases. Patients received three cycles of docetaxel (40 mg/m2, day 1), oxaliplatin (100 mg/m2, day 1), and S-1 (80–120 mg/body, days 1–14), followed by gastrectomy with D2 plus PAN dissection. Subsequently, patients underwent postoperative chemotherapy with S-1 for 1 year. The primary endpoint was major (grade ≥ 2a) pathological response rate (pRR) according to the Japanese Classification of Gastric Carcinoma criteria. Results Between October 2018 and March 2022, 47 patients (bulky N, 20; PAN, 17; both, 10) were enrolled in the trial. One patient was ineligible. Another declined any protocol treatments before initiation. Among the 45 eligible patients who initiated DOS chemotherapy, 44 (98%) completed 3 cycles and 42 (93%) underwent R0 resection. Major pRR and pathological complete response rates among the 46 eligible patients, including the patient who declined treatment, were 57% (26/46) and 24% (11/46), respectively. Common grade 3 or 4 toxicities were neutropenia (24%), anorexia (16%), febrile neutropenia (9%), and diarrhea (9%). No treatment-related deaths occurred. Conclusions Preoperative chemotherapy with DOS yielded favorable pathological responses with an acceptable toxicity profile. This multimodal approach is highly promising for treating gastric cancer with ELM.

Posterior and Para-Aortic (D2plus) Lymphadenectomy after Neoadjuvant/Conversion Therapy for Locally Advanced/Oligometastatic Gastric Cancer

“…Other experiences, mainly from Japan, have reported similar results. In particular, the JCOG 1704 trial enrolled 47 patients who received three cycles of docetaxel, oxaliplatin, and S-1 followed by D2plus lymphadenectomy: postoperative morbidity for grade III or higher was 11%, with no postoperative deaths [21].…”

“…After D2plus lymphadenectomy, a median (IQR) of 39 (30-56) total lymph nodes were removed; of these, a median of 25 (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) total lymph nodes were removed at the first level (stations 1 to 7), 6 (3-10) at the second level (stations 8 to 12), and 7 (4-13) at the third level (stations 8p, 12 b/p, 13, and 16) (Figure 1).…”

“…Currently, most studies evaluating the impact of D2plus lymphadenectomy after systemic chemotherapy are from East Asia. These include some phase II studies with limited series [17,21].…”

Preoperative docetaxel, cisplatin, and 5-fluorouracil for resectable locally advanced esophageal and esophagogastric junctional adenocarcinoma

“…The longer term results of this trial have since been reported and included a significantly higher 5-year OS rate in the group that received preoperative DOS (66.8 vs 63.0%) [ 10 ]. In Japan, where only gastric cancer has been treated, the efficacy of DOS therapy has been reported with a promising pathological complete response rate (24%) [ 11 ]. Although such promising regimens of FLOT and DOS have been reported, there are currently few reports on safety and efficacy in Japanese patients with EGJ-AC.…”