Maintenance Treatment With S-1 in Gastric Cancer Patients

Summary

Gastric cancer remains the third leading cause of cancer-related death worldwide and is especially frequent in East Asia. Fluoropyrimidines are the backbone of first-line chemotherapy for advanced gastric cancer (AGC), and S-1 provides new option with its simplicity and convenience. 5-Fluorouracil (5-FU) was the only efficacious treatment for AGC before the nineties of the 20th century, and afterwards with the discovery of chemotherapy such as cisplatin, oxaliplatin, S-1 and capecitabine, response rate as well as survival had been improved greatly. Most of AGC will progress after first-line treatment; therefore, seeking an efficient and low toxic maintaining regimen to prolong progression-free survival (PFS) becomes a hot topic in oncologic field. Some clinical researches demonstrated maintenance treatment for advanced colorectal cancer (CRC) and lung cancer. The investigators had conducted a phase III clinical trial that demonstrated capecitabine maintenance versus observation prolonged PFS significantly after first-line chemotherapy with FOLFOX or XELOX regimens in advanced CRC. In AGC, several retrospective studies revealed patients receiving 5-FU/leucovorin(LV), capecitabine, or trastuzumab maintaining therapy experienced significantly longer PFS than that stopped chemotherapy after first-line chemotherapy. Some one-arm phase II clinical trials found 5-FU/LV, capecitabine, S-1, capecitabine plus bevacirumab, or capecitabine plus bevacirumab plus trastuzumab maintenance seemed to yield sound PFS and good tolerance. However, there were no randomized controlled clinical trials for maintenance treatment of these regimens in AGC, except that a phase II Chinese randomized controlled trial of Uracil and Tegafur (UFT) versus observation experienced early termination. Above all, so far, there is no data to demonstrate that regular 2-6 months of chemotherapy followed by maintenance treatment could prolong PFS and OS for AGC. S-1 is effective for gastric cancer, and was approved as palliative treatment for advanced gastric cancer and adjuvant treatment; in addition, with its relative less frequency of side effects and convenient oral administration, S-1 as maintenance regimen could be prone to be accepted by patients. Therefore, the current study is designed to investigate that S-1 as maintenance treatment after first-line palliative chemotherapy could improve PFS and OS for patients with advanced gastric cancer through a perspective randomized clinical study.

Timeline

Start

2016-01-01

Primary completion

2018-12

Completion

2018-12

Publications

• Background Li W, Zhao X, Wang H, Liu X, Zhao X, Huang M, Qiu L, Zhang W, Chen Z, Guo W, Li J, Zhu X. Maintenance treatment of Uracil and Tegafur (UFT) in responders following first-line fluorouracil-based chemotherapy in metastatic gastric cancer: a randomized phase II study. Oncotarget. 2017 Jun 6;8(23):37826-37834. doi: 10.18632/oncotarget.13922.
• Background Qiu MZ, Wei XL, Zhang DS, Jin Y, Zhou YX, Wang DS, Ren C, Bai L, Luo HY, Wang ZQ, Wang FH, Li YH, Yang DJ, Xu RH. Efficacy and safety of capecitabine as maintenance treatment after first-line chemotherapy using oxaliplatin and capecitabine in advanced gastric adenocarcinoma patients: a prospective observation. Tumour Biol. 2014 May;35(5):4369-75. doi: 10.1007/s13277-013-1574-5. Epub 2014 Feb 11.
• Background Petrioli R, Francini E, Roviello F, Marrelli D, Miano ST, Fiaschi AI, Laera L, Bellini MA, Roviello G. Treatment of advanced oesophagogastric cancer with FOLFOX-4 regimen followed by leucovorin/bolus and continuous infusion 5-FU as maintenance chemotherapy in patients aged >/= 75 years with impaired performance status. J Geriatr Oncol. 2015 Sep;6(5):380-6. doi: 10.1016/j.jgo.2015.06.002. Epub 2015 Jul 27.
• Background Eren OO, Ozturk MA, Sonmez OU, Oyan B. Safety, Feasibility, and Efficacy of Capecitabine Maintenance in Patients With Advanced Gastric Cancer: A Retrospective Study. Am J Ther. 2016 Nov/Dec;23(6):e1493-e1497. doi: 10.1097/MJT.0000000000000156.
• Background Chen J, Shen W, Xia J, Xu R, Zhu M, Xu M. [Effect of S-1 maintenance chemotherapy following DCF regimen in patients with advanced gastric cancer]. Nan Fang Yi Ke Da Xue Xue Bao. 2014 Jun;34(7):1057-60. Chinese.
• Background Meulendijks D, de Groot JW, Los M, Boers JE, Beerepoot LV, Polee MB, Beeker A, Portielje JE, Goey SH, de Jong RS, Vanhoutvin SA, Kuiper M, Sikorska K, Pluim D, Beijnen JH, Schellens JH, Grootscholten C, Tesselaar ME, Cats A. Bevacizumab combined with docetaxel, oxaliplatin, and capecitabine, followed by maintenance with capecitabine and bevacizumab, as first-line treatment of patients with advanced HER2-negative gastric cancer: A multicenter phase 2 study. Cancer. 2016 May 1;122(9):1434-43. doi: 10.1002/cncr.29864. Epub 2016 Mar 11.
• Background Meulendijks D, Beerepoot LV, Boot H, de Groot JW, Los M, Boers JE, Vanhoutvin SA, Polee MB, Beeker A, Portielje JE, de Jong RS, Goey SH, Kuiper M, Sikorska K, Beijnen JH, Tesselaar ME, Schellens JH, Cats A. Trastuzumab and bevacizumab combined with docetaxel, oxaliplatin and capecitabine as first-line treatment of advanced HER2-positive gastric cancer: a multicenter phase II study. Invest New Drugs. 2016 Feb;34(1):119-28. doi: 10.1007/s10637-015-0309-4. Epub 2015 Dec 8.
• Background Palacio S, Loaiza-Bonilla A, Kittaneh M, Kyriakopoulos C, Ochoa RE, Escobar M, Arango B, Restrepo MH, Merchan JR, Rocha Lima CM, Hosein PJ. Successful use of Trastuzumab with anthracycline-based chemotherapy followed by trastuzumab maintenance in patients with advanced HER2-positive gastric cancer. Anticancer Res. 2014 Jan;34(1):301-6.
• Background Luo HY, Li YH, Wang W, Wang ZQ, Yuan X, Ma D, Wang FH, Zhang DS, Lin DR, Lin YC, Jia J, Hu XH, Peng JW, Xu RH. Single-agent capecitabine as maintenance therapy after induction of XELOX (or FOLFOX) in first-line treatment of metastatic colorectal cancer: randomized clinical trial of efficacy and safety. Ann Oncol. 2016 Jun;27(6):1074-1081. doi: 10.1093/annonc/mdw101. Epub 2016 Mar 2.

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