Neoadjuvant Chemotherapy Versus Neoadjuvant Chemoradiotherapy for Resectable Locally Advanced Esophageal Cancer (HCHTOG1903)

Summary

Multimodal treatment combining surgery with chemotherapy and/or radiotherapy is necessary to improve the chances of survival in patients with locally advanced thoracic esophageal cancer. However, there is no consensus about the neoadjuvant treatment for resectable locally advanced esophageal squamous cell carcinoma. The aim of current randomized controlled clinical trail is to investigate the impact of neoadjuvant chemotherapy plus surgery and neoadjuvant chemoradiation therapy plus surgery on overall survival for patients with resectable locally advanced esophageal squamous cell carcinoma. The investigators plan to enroll 456 patients with locally advanced esophageal squamous cell carcinoma in 3 years. Eligible patients will be randomized into neoadjuvant chemotherapy group (paclitaxel 175mg/m2 plus cisplatin 75mg/m2, q21d, 2 cycles) or neoadjuvant chemoradiation group (41.4Gy, 1.8Gy\*23d plus paclitaxel 50mg/m2 plus carboplatin AUC=2, q1w, 5 cycles). The primary endpoint is 5 year overall survival and the secondary endpoints include 5 year disease-free survival, adverse events, pathologic complete response, postoperative complications, quality of life. The biomarkers predicting the sensitivity of neoadjuvant therapy will be explored.

Timeline

Start

2019-10-22

Primary completion

2023-12-21

Completion

2028-12-21

Publications

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• Background Yamasaki M, Yasuda T, Yano M, Hirao M, Kobayashi K, Fujitani K, Tamura S, Kimura Y, Miyata H, Motoori M, Shiraishi O, Makino T, Satoh T, Mori M, Doki Y. Multicenter randomized phase II study of cisplatin and fluorouracil plus docetaxel (DCF) compared with cisplatin and fluorouracil plus Adriamycin (ACF) as preoperative chemotherapy for resectable esophageal squamous cell carcinoma (OGSG1003). Ann Oncol. 2017 Jan 1;28(1):116-120. doi: 10.1093/annonc/mdw439.
• Background Mariette C, Dahan L, Mornex F, Maillard E, Thomas PA, Meunier B, Boige V, Pezet D, Robb WB, Le Brun-Ly V, Bosset JF, Mabrut JY, Triboulet JP, Bedenne L, Seitz JF. Surgery alone versus chemoradiotherapy followed by surgery for stage I and II esophageal cancer: final analysis of randomized controlled phase III trial FFCD 9901. J Clin Oncol. 2014 Aug 10;32(23):2416-22. doi: 10.1200/JCO.2013.53.6532. Epub 2014 Jun 30.
• Background Shapiro J, van Lanschot JJB, Hulshof MCCM, van Hagen P, van Berge Henegouwen MI, Wijnhoven BPL, van Laarhoven HWM, Nieuwenhuijzen GAP, Hospers GAP, Bonenkamp JJ, Cuesta MA, Blaisse RJB, Busch ORC, Ten Kate FJW, Creemers GM, Punt CJA, Plukker JTM, Verheul HMW, Bilgen EJS, van Dekken H, van der Sangen MJC, Rozema T, Biermann K, Beukema JC, Piet AHM, van Rij CM, Reinders JG, Tilanus HW, Steyerberg EW, van der Gaast A; CROSS study group. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol. 2015 Sep;16(9):1090-1098. doi: 10.1016/S1470-2045(15)00040-6. Epub 2015 Aug 5.
• Background van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen MI, Wijnhoven BP, Richel DJ, Nieuwenhuijzen GA, Hospers GA, Bonenkamp JJ, Cuesta MA, Blaisse RJ, Busch OR, ten Kate FJ, Creemers GJ, Punt CJ, Plukker JT, Verheul HM, Spillenaar Bilgen EJ, van Dekken H, van der Sangen MJ, Rozema T, Biermann K, Beukema JC, Piet AH, van Rij CM, Reinders JG, Tilanus HW, van der Gaast A; CROSS Group. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012 May 31;366(22):2074-84. doi: 10.1056/NEJMoa1112088.
• Background Yang H, Liu H, Chen Y, Zhu C, Fang W, Yu Z, Mao W, Xiang J, Han Y, Chen Z, Yang H, Wang J, Pang Q, Zheng X, Yang H, Li T, Lordick F, D'Journo XB, Cerfolio RJ, Korst RJ, Novoa NM, Swanson SJ, Brunelli A, Ismail M, Fernando HC, Zhang X, Li Q, Wang G, Chen B, Mao T, Kong M, Guo X, Lin T, Liu M, Fu J; AME Thoracic Surgery Collaborative Group. Neoadjuvant Chemoradiotherapy Followed by Surgery Versus Surgery Alone for Locally Advanced Squamous Cell Carcinoma of the Esophagus (NEOCRTEC5010): A Phase III Multicenter, Randomized, Open-Label Clinical Trial. J Clin Oncol. 2018 Sep 20;36(27):2796-2803. doi: 10.1200/JCO.2018.79.1483. Epub 2018 Aug 8.
• Background Gebski V, Burmeister B, Smithers BM, Foo K, Zalcberg J, Simes J; Australasian Gastro-Intestinal Trials Group. Survival benefits from neoadjuvant chemoradiotherapy or chemotherapy in oesophageal carcinoma: a meta-analysis. Lancet Oncol. 2007 Mar;8(3):226-34. doi: 10.1016/S1470-2045(07)70039-6.
• Background Stahl M, Walz MK, Stuschke M, Lehmann N, Meyer HJ, Riera-Knorrenschild J, Langer P, Engenhart-Cabillic R, Bitzer M, Konigsrainer A, Budach W, Wilke H. Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction. J Clin Oncol. 2009 Feb 20;27(6):851-6. doi: 10.1200/JCO.2008.17.0506. Epub 2009 Jan 12.
• Background Nakamura K, Kato K, Igaki H, Ito Y, Mizusawa J, Ando N, Udagawa H, Tsubosa Y, Daiko H, Hironaka S, Fukuda H, Kitagawa Y; Japan Esophageal Oncology Group/Japan Clinical Oncology Group. Three-arm phase III trial comparing cisplatin plus 5-FU (CF) versus docetaxel, cisplatin plus 5-FU (DCF) versus radiotherapy with CF (CF-RT) as preoperative therapy for locally advanced esophageal cancer (JCOG1109, NExT study). Jpn J Clin Oncol. 2013 Jul;43(7):752-5. doi: 10.1093/jjco/hyt061. Epub 2013 Apr 26.
• Background Tang H, Tan L, Shen Y, Wang H, Lin M, Feng M, Xu S, Guo W, Qian C, Liu T, Zeng Z, Hou Y, Yu Z, Jiang H, Li Z, Chen C, Lian C, Du M, Li H, Xie D, Yin J, Zhao N, Wang Q. CMISG1701: a multicenter prospective randomized phase III clinical trial comparing neoadjuvant chemoradiotherapy to neoadjuvant chemotherapy followed by minimally invasive esophagectomy in patients with locally advanced resectable esophageal squamous cell carcinoma (cT3-4aN0-1M0) (NCT03001596). BMC Cancer. 2017 Jun 28;17(1):450. doi: 10.1186/s12885-017-3446-7.
• Background Klevebro F, Alexandersson von Dobeln G, Wang N, Johnsen G, Jacobsen AB, Friesland S, Hatlevoll I, Glenjen NI, Lind P, Tsai JA, Lundell L, Nilsson M. A randomized clinical trial of neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the oesophagus or gastro-oesophageal junction. Ann Oncol. 2016 Apr;27(4):660-7. doi: 10.1093/annonc/mdw010. Epub 2016 Jan 17.
• Sun HB, Xing WQ, Liu XB, Zheng Y, Yang SJ, Wang ZF, Liu SL, Ba YF, Zhang RX, Liu BX, Fan CC, Chen PN, Liang GH, Yu YK, Liu Q, Wang HR, Li HM, Li ZX; written on Henan Cancer Hospital Thoracic Oncology Group (HCHTOG). Neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for locally advanced oesophageal squamous cell carcinoma: a single-Centre, open-label, randomized, controlled, clinical trial (HCHTOG1903). BMC Cancer. 2020 Apr 15;20(1):303. doi: 10.1186/s12885-020-06824-2.

Drugs

Indications