ESOPEC: prospective randomized controlled multicenter phase III trial comparing perioperative chemotherapy (FLOT protocol) to neoadjuvant chemoradiation (CROSS protocol) in patients with adenocarcinoma of the esophagus (NCT02509286)

Jens Hoeppner, Florian Lordick, Thomas Brunner, Torben Glatz, Peter Bronsert, Nadine Röthling, Claudia Schmoor, Dietmar Lorenz, Christian Ell, Ulrich T Hopt, J Rüdiger Siewert, Jens Hoeppner, Florian Lordick, Thomas Brunner, Torben Glatz, Peter Bronsert, Nadine Röthling, Claudia Schmoor, Dietmar Lorenz, Christian Ell, Ulrich T Hopt, J Rüdiger Siewert

Abstract

Background: Recent randomized controlled trials comparing neoadjuvant chemoradiation plus surgery or perioperative chemotherapy plus surgery with surgery alone showed significant survival benefits for combined modality treatment of patients with localized esophageal adenocarcinoma. However, head-to-head comparisons of neoadjuvant chemoradiation and perioperative chemotherapy applying contemporary treatment protocols are lacking. The present trial was initiated to obtain valid information whether neoadjuvant chemoradiation or perioperative chemotherapy yields better survival in the treatment of localized esophageal adenocarcinoma.

Methods/design: The ESOPEC trial is an investigator-initiated multicenter prospective randomized controlled two-arm trial, comparing the efficacy of neoadjuvant chemoradiation (CROSS protocol: 41.4Gy plus carboplatin/paclitaxel) followed by surgery versus perioperative chemotherapy and surgery (FLOT protocol: 5-FU/leucovorin/oxaliplatin/docetaxel) for the curative treatment of localized esophageal adenocarcinoma. Patients with cT1cN + cM0 and cT2-4acNxcM0 esophageal and junctional adenocarcinoma are eligible. The trial aims to include 438 participants who are centrally randomized to one of the two treatment groups in a 1:1 ratio stratified by N-stage and study site. The primary endpoint of the trial is overall survival assessed with a minimum follow-up of 36 months. Secondary objectives are progression-free survival, recurrence-free survival, site of failure, postoperative morbidity and mortality, duration of hospitalization as well as quality of life.

Discussion: The ESOPEC trial compares perioperative chemotherapy according to the FLOT protocol to neoadjuvant chemoradiation according to the CROSS protocol in multimodal treatment of non-metastasized recectable adenocarcinoma of the esophagus and the gastroesophageal junction. The goal of the trial is identify the superior protocol with regard to patient survival, treatment morbidity and quality of life.

Trial registration: NCT02509286 (July 22, 2015).

Keywords: Adenocarcinoma; Esophageal cancer; Neoadjuvant chemoradiation; Perioperative chemotherapy.

Figures

Fig. 1
Fig. 1
Trial diagram of the ESOPEC trial
Fig. 2
Fig. 2
Treatment and visit week scheme of the ESOPEC trial
Fig. 3
Fig. 3
Schedule of enrolment, interventions and assessments of the ESOPEC trial

References

    1. Hulscher JB, van Sandick JW, de Boer AG, et al. Extended transthoracic resection compared with limited transhiatal resection for adenocarcinoma of the esophagus. N Engl J Med. 2002;347(21):1662–9. doi: 10.1056/NEJMoa022343.
    1. Moehler M, Baltin CT, Ebert M, et al. International comparison of the German evidence-based S3-guidelines on the diagnosis and multimodal treatment of early and locally advanced gastric cancer, including adenocarcinoma of the lower esophagus. Gastric Cancer. 2015;18(3):550–63. doi: 10.1007/s10120-014-0403-x.
    1. van Hagen P, Hulshof MC, van Lanschot JJ, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;366(22):2074–84. doi: 10.1056/NEJMoa1112088.
    1. Sjoquist KM, Burmeister BH, Smithers BM, et al. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol. 2011;12(7):681–92. doi: 10.1016/S1470-2045(11)70142-5.
    1. Ronellenfitsch U, Schwarzbach M, Hofheinz R, et al. Perioperative chemo(radio)therapy versus primary surgery for resectable adenocarcinoma of the stomach, gastroesophageal junction, and lower esophagus. Cochrane Database Syst Rev. 2013;5:CD008107.
    1. Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355(1):11–20. doi: 10.1056/NEJMoa055531.
    1. Ychou M, Boige V, Pignon JP, 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(13):1715–21. doi: 10.1200/JCO.2010.33.0597.
    1. Homann N, Pauligk C, Luley K, et al. Pathological complete remission in patients with oesophagogastric cancer receiving preoperative 5-fluorouracil, oxaliplatin and docetaxel. Int J Cancer. 2012;130(7):1706–13. doi: 10.1002/ijc.26180.
    1. Lorenzen S, Pauligk C, Homann N, et al. Feasibility of perioperative chemotherapy with infusional 5-FU, leucovorin, and oxaliplatin with (FLOT) or without (FLO) docetaxel in elderly patients with locally advanced esophagogastric cancer. Br J Cancer. 2013;108(3):519–26. doi: 10.1038/bjc.2012.588.
    1. Hoeppner J, Zirlik K, Brunner T, et al. Multimodal treatment of locally advanced esophageal adenocarcinoma: Which regimen should we choose? Outcome analysis of perioperative chemotherapy versus neoadjuvant chemoradiation in 105 patients. J Surg Oncol. 2014;109(3):287–93. doi: 10.1002/jso.23498.
    1. Stahl M, Walz MK, Stuschke M, et al. Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction. J Clin Oncol. 2009;27(6):851–6. doi: 10.1200/JCO.2008.17.0506.
    1. Reim D, Gertler R, Novotny A, et al. Adenocarcinomas of the esophagogastric junction are more likely to respond to preoperative chemotherapy than distal gastric cancer. Ann Surg Oncol. 2012;19(7):2108–18. doi: 10.1245/s10434-011-2147-8.
    1. Lorenzen S, Thuss-Patience P, Al-Batran SE, et al. Impact of pathologic complete response on disease-free survival in patients with esophagogastric adenocarcinoma receiving preoperative docetaxel-based chemotherapy. Ann Oncol. 2013;24(8):2068–73. doi: 10.1093/annonc/mdt141.
    1. Lagergren J, Mattsson F. Diverging trends in recent population-based survival rates in oesophageal and gastric cancer. PLoS One. 2012;7(7):e41352. doi: 10.1371/journal.pone.0041352.
    1. Sobin LH, Gospodarowicz MK, Wittekind C, editors. International Union Against Cancer (UICC) TNM Classification of Malignant Tumors. 7. Oxford, UK: Wiley-Blackwell; 2009.
    1. Becker K, Mueller JD, Schulmacher C, et al. Histomorphology and grading of regression in gastric carcinoma treated with neoadjuvant chemotherapy. Cancer. 2003;98(7):1521–30. doi: 10.1002/cncr.11660.
    1. Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR, the Hospital Infection Control Practices Advisory Committee Guideline for the prevention of surgical site infection, 1999. Infect Control Hosp Epidemiol. 1999;20:247–28. doi: 10.1086/501620.
    1. Makowiec F, Baier P, Kulemann B, et al. Improved long-term survival after esophagectomy for esophageal cancer: Influence of epidemiologic shift and neoadjuvant therapy. J Gastrointest Surg. 2013;17:1193–201. doi: 10.1007/s11605-013-2212-7.
    1. Ruol A, Castoro C, Portale G, et al. Trends in management and prognosis for esophageal cancer surgery: Twenty-five years of experience at a single institution. Arch Surg. 2009;144:247–54. doi: 10.1001/archsurg.2008.574.
    1. Siewert JR, Stein HJ, Feith M, et al. Histologic tumor type is an independent prognostic parameter in esophageal cancer: Lessons from more than 1,000 consecutive resections at a single center in the Western world. Ann Surg. 2001;234:360–7. doi: 10.1097/00000658-200109000-00010.
    1. van Meerten E, Muller K, Tilanus HW, et al. Neoadjuvant concurrent chemoradiation with weekly paclitaxel and carboplatin for patients with oesophageal cancer: a phase II study. Br J Cancer. 2006;94(10):1389–94. doi: 10.1038/sj.bjc.6603134.

Source: PubMed

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