A phase II study of perioperative capecitabine plus oxaliplatin (CapeOx) therapy for advanced gastric cancer with multiple lymph node metastases (OGSG 1701).
Authors: Endo Shunji , Kimura Yutaka , Sugimoto Naotoshi , Kawabata Ryohei , Takeno Atsushi , Matsuyama Jin , Imano Motohiro , Kawakami Hisato , Tamura Shigeyuki , Nakamura Masato , Takeshita Hiroki , Boku Shogen , Kurokawa Yukinori , Shimokawa Toshio , Satoh Taroh 
Published: January 2024

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Background: Gastric cancer with paraaortic lymph node metastasis or bulky lymph node metastasis is difficult to undergo curative resection without preoperative chemotherapy. Even if curative resection can be performed, the prognosis is extremely poor. The purpose of this study was to evaluate the efficacy and safety of perioperative capecitabine plus oxaliplatin combined chemotherapy (CapeOx) for such advanced gastric cancer with multiple lymph node metastases. Methods: In this phase II trial, eligibility criteria were as follows; histologically proven gastric carcinoma; HER2 negative or unknown; with paraaortic lymph node metastases (#16a2/16b1) > 10 mm and/or bulky lymph node metastases located at celiac axis, common hepatic artery, splenic artery and/or upper mesenteric vein which make a huge bulk > 3.0 cm and/or multiple large bulks > 1.5 cm; without any other metastatic lesions; not a large (≥ 8 cm) type 3 or type 4 gastric cancer; and age between 20 and 80 years old. Treatment included three cycles of preoperative CapeOx (capecitabine; 2,000 mg/m2 for 14 days, oxaliplatin; 130 mg/m2 day 1) every 3 weeks, followed by five cycles of postoperative CapeOx after radical gastrectomy. The primary endpoint was response rate according to the RECIST v1.0. The planned sample size was 30 patients calculated on the hypothesis that the expected response rate was 65% and the threshold was 50%, with one-sided alpha of 0.05 and the power of 90%. Results: Thirty patients from 14 institutions were enrolled from September 2017 to June 2022. The number of patients with compete response, partial response, stable disease, progressive disease, and inevaluable were, 0, 20, 8, 1, and 1, respectively. The response rate was 66.7%, with the 90% confidence interval of 50.1 - 80.7% ( p = 0.049). The curative resection rate was 93.3%. The protocol treatment completion rate was 53.3%. The preoperative chemotherapy completion rate was 93.3%. The operation completion rate was 90.0%. The postoperative chemotherapy completion rate was 70.0%. The relative dose intensities were 94.8% for capecitabine and 95.2% for oxaliplatin on preoperative CapeOx, and 80.8% for capecitabine and 64.2% for oxaliplatin on postoperative CapeOx. The histological response rate (Grade ≥ 1b) was 66.7%. The adverse events of Grade ≥ 3 included neutropenia in 3.3%, anemia in 6.7%, and anorexia in 10% on preoperative CapeOx, and neutropenia in 23.8% and diarrhea in 9.5% on postoperative CapeOx. The final results of the survival analysis are yet to come. Conclusions: Perioperative CapeOx therapy for advanced gastric cancer with multiple lymph node metastasis showed favorable response rate, curative resection rate and acceptable adverse events, and was considered a promising treatment regimen. Clinical trial information: UMIN000028749 .