Journal of Gastric Cancer

The Korean Gastric Cancer Association (대한위암학회)
권호 표지
DOI QR코드

DOI QR Code

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

  • Xiang, Xiao-song (Jinling Hospital Research Institute of General Surgery, School of Medicine, Nanjing University) ;
  • Su, Yu (Department of General Medicine, Jinling Hospital, School of Medicine, Nanjing University) ;
  • Li, Guo-li (Jinling Hospital Research Institute of General Surgery, School of Medicine, Nanjing University) ;
  • Ma, Long (Jinling Hospital Research Institute of General Surgery, School of Medicine, Nanjing University) ;
  • Zhou, Chang-sheng (Jinling Hospital Medical Imaging Center, School of Medicine, Nanjing University) ;
  • Ma, Ru-feng (Jinling Hospital Research Institute of General Surgery, School of Medicine, Nanjing University)
  • Received : 2020.07.28
  • Accepted : 2020.11.14
  • Published : 2020.12.31
Download PDF
⟨ Previous Next ⟩

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.

Keywords

References

  1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015;65:87-108. https://doi.org/10.3322/caac.21262
  2. An JY, Kang TH, Choi MG, Noh JH, Sohn TS, Kim S. Borrmann type IV: an independent prognostic factor for survival in gastric cancer. J Gastrointest Surg 2008;12:1364-1369. https://doi.org/10.1007/s11605-008-0516-9
  3. Ahn JB, Ha TK, Lee HR, Kwon SJ. An insufficient preoperative diagnosis of Borrmann type 4 gastric cancer in spite of EMR. J Gastric Cancer 2011;11:59-63. https://doi.org/10.5230/jgc.2011.11.1.59
  4. Miki Y, Tokunaga M, Tanizawa Y, Bando E, Kawamura T, Terashima M. Staging laparoscopy for patients with cM0, type 4, and large type 3 gastric cancer. World J Surg 2015;39:2742-2747. https://doi.org/10.1007/s00268-015-3144-z
  5. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A. AJCC Cancer Staging Manual. 7th ed. Berlin: Springer, 2010.
  6. Sobin LH, Gospodarowicz MK, Wittekind C. TNM Classification of Malignant Tumours. 7th ed. Hoboken: Wiley-Blackwell, 2009.
  7. Japanese Gastric Cancer Association. Japanese classification of gastric carcinoma: 3rd English edition. Gastric Cancer 2011;14:101-112. https://doi.org/10.1007/s10120-011-0041-5
  8. Blackham AU, Swords DS, Levine EA, Fino NF, Squires MH, Poultsides G, et al. Is linitis plastica a contraindication for surgical resection: a multi-institution study of the U.S. Gastric Cancer Collaborative. Ann Surg Oncol 2016;23:1203-1211. https://doi.org/10.1245/s10434-015-4947-8
  9. Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 2006;355:11-20. https://doi.org/10.1056/NEJMoa055531
  10. Al-Batran SE, Homann N, Pauligk C, Goetze TO, Meiler J, Kasper S, et al. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. Lancet 2019;393:1948-1957. https://doi.org/10.1016/S0140-6736(18)32557-1
  11. Terashima M, Iwasaki Y, Mizusawa J, Katayama H, Nakamura K, Katai H, et al. 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). Gastric Cancer 2019;22:1044-1052. https://doi.org/10.1007/s10120-019-00941-z
  12. He Q, Li Y, Ma L, Ji X, Li G. Application of FLEEOX preoperative chemotherapy via intra-arterial and intravenous administration in treatment of unresectable locally advanced gastric cancer. J Gastrointest Surg 2016;20:1421-1427. https://doi.org/10.1007/s11605-016-3153-8
  13. Li Y, Chen J, He Q, Ji X, Wang X, Fan C, et al. Clinical efficacy of neoadjuvant chemotherapy regimens FLEEOX vs. XELOX in patients with initially unresectable advanced gastric cancer: a propensity score analysis. Oncotarget 2017;8:86886-86896. https://doi.org/10.18632/oncotarget.19004
  14. Japanese Research Society for Gastric Cancer. Japanese Classification of Gastric Carcinoma. 1st ed. Tokyo: Kanehara & Co. Ltd., 1995.
  15. Becker K, Mueller JD, Schulmacher C, Ott K, Fink U, Busch R, et al. Histomorphology and grading of regression in gastric carcinoma treated with neoadjuvant chemotherapy. Cancer 2003;98:1521-1530. https://doi.org/10.1002/cncr.11660
  16. Iwasaki Y, Sasako M, Yamamoto S, Nakamura K, Sano T, Katai H, et al. Phase II study of preoperative chemotherapy with S-1 and cisplatin followed by gastrectomy for clinically resectable type 4 and large type 3 gastric cancers (JCOG0210). J Surg Oncol 2013;107:741-745. https://doi.org/10.1002/jso.23301
  17. Nazli O, Derici H, Tansug T, Yaman I, Bozdag AD, Isgüder AS, et al. Survival analysis after surgical treatment of gastric cancer: review of 121 cases. Hepatogastroenterology 2007;54:625-629.
  18. Liang C, Chen G, Zhao B, Qiu H, Li W, Sun X, et al. Borrmann type IV gastric cancer: focus on the role of gastrectomy. J Gastrointest Surg 2020;24:1026-1032. https://doi.org/10.1007/s11605-019-04236-7
  19. Otsuji E, Kuriu Y, Okamoto K, Ochiai T, Ichikawa D, Hagiwara A, et al. Outcome of surgical treatment for patients with scirrhous carcinoma of the stomach. Am J Surg 2004;188:327-332. https://doi.org/10.1016/j.amjsurg.2004.06.010
  20. Takahashi I, Matsusaka T, Onohara T, Nishizaki T, Ishikawa T, Tashiro H, et al. Clinicopathological features of long-term survivors of scirrhous gastric cancer. Hepatogastroenterology 2000;47:1485-1488.
  21. Park SH, Sohn TS, Lee J, Lim DH, Hong ME, Kim KM, et al. Phase III trial to compare adjuvant chemotherapy with capecitabine and cisplatin versus concurrent chemoradiotherapy in gastric cancer: final report of the adjuvant chemoradiotherapy in stomach tumors trial, including survival and subset analyses. J Clin Oncol 2015;33:3130-3136. https://doi.org/10.1200/JCO.2014.58.3930
  22. Smalley SR, Benedetti JK, Haller DG, Hundahl SA, Estes NC, Ajani JA, et al. Updated analysis of SWOGdirected intergroup study 0116: a phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection. J Clin Oncol 2012;30:2327-2333. https://doi.org/10.1200/JCO.2011.36.7136
  23. Janjigian YY, Bendell J, Calvo E, Kim JW, Ascierto PA, Sharma P, et al. CheckMate-032 study: efficacy and safety of nivolumab and nivolumab plus ipilimumab in patients with metastatic esophagogastric cancer. J Clin Oncol 2018;36:2836-2844. https://doi.org/10.1200/jco.2017.76.6212
  24. U.S. National Library of Medicine. Study of pembrolizumab (MK-3475) as first-line monotherapy and combination therapy for treatment of advanced gastric or gastroesophageal junction adenocarcinoma (MK-3475-062/KEYNOTE-062) [Internet]. Bethesda (MD): U.S. National Library of Medicine; 2020 [cited 2020 Jun 8]. Available from: https://clinicaltrials.gov/ct2/show/NCT02494583.
  25. Yashiro M, Hirakawa K. Cancer-stromal interactions in scirrhous gastric carcinoma. Cancer Microenviron 2010;3:127-135. https://doi.org/10.1007/s12307-010-0036-5
  26. Ilson DH. Advances in the treatment of gastric cancer: 2019. Curr Opin Gastroenterol 2019;35:551-554. https://doi.org/10.1097/mog.0000000000000577
  27. Ong ES, Poirier M, Espat NJ. Hepatic intra-arterial chemotherapy. Ann Surg Oncol 2006;13:142-149. https://doi.org/10.1245/ASO.2006.01.005
  28. Yasufuku I, Nunobe S, Ida S, Kumagai K, Ohashi M, Hiki N, et al. Conversion therapy for peritoneal lavage cytology-positive type 4 and large type 3 gastric cancer patients selected as candidates for R0 resection by diagnostic staging laparoscopy. Gastric Cancer 2020;23:319-327. https://doi.org/10.1007/s10120-019-00994-0