Study protocol of a randomized phase III trial of comparing preoperative chemoradiation with preoperative chemotherapy in patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma: PREACT

Xiaowen Liu, Jiejie Jin, Hong Cai, Hua Huang, Guangfa Zhao, Ye Zhou, Jianghong Wu, Chunyan Du, Ziwen Long, Yantian Fang, Mingze Ma, Guichao Li, Menglong Zhou, Jiliang Yin, Xiaodong Zhu, Ji Zhu, Weiqi Sheng, Dan Huang, Hui Zhu, Zhaozhen Zhang, Qi Lu, Li Xie, Zhen Zhang, Yanong Wang, Xiaowen Liu, Jiejie Jin, Hong Cai, Hua Huang, Guangfa Zhao, Ye Zhou, Jianghong Wu, Chunyan Du, Ziwen Long, Yantian Fang, Mingze Ma, Guichao Li, Menglong Zhou, Jiliang Yin, Xiaodong Zhu, Ji Zhu, Weiqi Sheng, Dan Huang, Hui Zhu, Zhaozhen Zhang, Qi Lu, Li Xie, Zhen Zhang, Yanong Wang

Abstract

Background: The prognosis of patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma is still dismal. There are no standard treatment strategies for these patients. Multidisciplinary team (MDT) approach is a good choice for making a high-quality decision. Generally, MDT will recommend these patients to receive preoperative chemotherapy or preoperative chemoradiation based on all kinds of treatment guidelines. However, the preferred preoperative treatment is still not established. In order to solve this problem, we carry out this randomized phase III trial of comparing preoperative chemoradiation with preoperative chemotherapy in patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma.

Methods: Eligible patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma are randomized to receive preoperative chemoradiation or preoperative chemotherapy, followed by surgery and postoperative chemotherapy. In the preoperative chemoradiation arm (Pre-CRT), patients receive two cycles of S-1 and oxaliplatin (SOX), chemoradiation, then followed by surgery and three more cycles of SOX chemotherapy. In the preoperative chemotherapy arm (Pre-CT), patients receive three cycles of SOX, following surgery three more cycles of SOX are given. The primary endpoint of this trial is to verify that preoperative chemoradiation could significantly improve the 3-year disease free survival (DFS) of patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma compared to preoperative chemotherapy.

Discussion: The results from this trial will provide important information about whether preoperative chemoradiation could improve survival compared to preoperative chemotherapy among patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma.

Trial registration: ClinicalTrials.gov Identifier: NCT03013010. First posted January 6, 2017.

Keywords: Adjuvant chemotherapy; Esophagogastric junction adenocarcinoma; Gastrectomy; Gastric cancer; Preoperative Chemoradiation; Preoperative chemotherapy.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flow chart
Fig. 2
Fig. 2
Chemotherapy schedule
Fig. 3
Fig. 3
Chemoradiation schedule

References

    1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2014;136:E359–E386. doi: 10.1002/ijc.29210.
    1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Gastric Cancer, V.1.2016. Available at physician_gls/pdf/gastric.pdf.
    1. Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355:11–20. doi: 10.1056/NEJMoa055531.
    1. Ychou M, Boige V, Pignon J-P, et al. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011;29:1715–1721. doi: 10.1200/JCO.2010.33.0597.
    1. Walsh TN, Noonan N, Hollywood D, et al. A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med. 1996;335:462–467. doi: 10.1056/NEJM199608153350702.
    1. Ajani JA, Mansfield PF, Janjan N, et al. Multi-institutional trial of preoperative chemoradiotherapy in patients with potentially resectable gastric carcinoma. J Clin Oncol. 2004;22:2774–2780. doi: 10.1200/JCO.2004.01.015.
    1. Ajani JA, Mansfield PF, Crane CH, et al. Paclitaxel-based chemoradiotherapy in localized gastric carcinoma: degree of pathologic response and not clinical parameters dictated patient outcome. J Clin Oncol. 2005;23:1237–1244. doi: 10.1200/JCO.2005.01.305.
    1. Liu Xiaowen, Li Guichao, Long Ziwen, Yin Jiliang, Zhu Xiaodong, Sheng Weiqi, Huang Dan, Zhu Hui, Zhang Zhaozhen, Cai Hong, Huang Hua, Zhao Guangfa, Zhou Ye, Zhang Zhen, Wang Yanong. Phase II trial of preoperative chemoradiation plus perioperative SOX chemotherapy in patients with locally advanced gastric cancer. Journal of Surgical Oncology. 2017;117(4):692–698. doi: 10.1002/jso.24917.
    1. Stahl M, Walz MK, Stuschke M, et al. Phase III comparing of preoperative chemotherapy with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction. J Clin Oncol. 2009;27:851–856. doi: 10.1200/JCO.2008.17.0506.
    1. Koizumi W, Takiuchi H, Yamada Y, et al. Phase II study of oxaliplatin plus S-1 as first-line treatment for advanced gastric cancer (G-SOX study) Ann Oncol. 2010;21(5):1001–1005. doi: 10.1093/annonc/mdp464.
    1. Oh SY, Kwon HC, Jeong SH, et al. A phase II study of S-1 and oxaliplatin (SOX) combination chemotherapy as a first-line therapy for patients with advanced gastric cancer. Investig New Drugs. 2012;30(1):350–356. doi: 10.1007/s10637-010-9507-2.
    1. Liu X, Xu Y, Long Z, Zhu H, Wang Y. Prognostic significance of tumor size in T3 gastric cancer. Ann Surg Oncol. 2009;16:1875–1882. doi: 10.1245/s10434-009-0449-x.
    1. Bang YJ, Kim YW, Yang HK, Chung HC, Park K, Lee KH, et al. Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASS): a phase 3 open-label, randomised controlled trial. Lancet. 2012;28:315–321. doi: 10.1016/S0140-6736(11)61873-4.
    1. Yamada Y, Higuchi K, Nishikawa K, Gotoh M, Fuse N, Sugimoto N, Nishina T, et al. Phase III study comparing oxaliplatin plus S-1 with cisplatin plus S-1 in chemotherapy-naïve patients with advanced gastric cancer. Ann Oncol. 2015;26:141–148. doi: 10.1093/annonc/mdu472.
    1. Jiang CG, Xu Y, Wang ZN, Sun Z, Liu FN, Yu M, Xu HM. Clinicopathological analysis and prognostic significance of peritoneal cytology in Chinese patients wit advanced gastric cancer. ANZ J Surg. 2011;81:608–613. doi: 10.1111/j.1445-2197.2010.05536.x.
    1. Leong T, Smithers BM, Michael M, Gebski V, Boussioutas A, Miller D, Simes J, et al. TOPGEAR: a randomised phase III trial of perioperative ECF chemotherapy versus preoperative chemoradiation plus perioperative ECF chemotherapy for resectable gastric cancer (an international, intergroup trial of the AGITG/TROG/EORTC/NCICCTG) BMC Cancer. 2015;15:532. doi: 10.1186/s12885-015-1529-x.

Source: PubMed

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

3
Abonner