Preoperative chemoradiation with paclitaxel-carboplatin or with fluorouracil-oxaliplatin-folinic acid (FOLFOX) for resectable esophageal and junctional cancer: the PROTECT-1402, randomized phase 2 trial

Mathieu Messager, Xavier Mirabel, Emmanuelle Tresch, Amaury Paumier, Véronique Vendrely, Laetitia Dahan, Olivier Glehen, Frederique Vasseur, Thomas Lacornerie, Guillaume Piessen, Farid El Hajbi, William B Robb, Stéphanie Clisant, Andrew Kramar, Christophe Mariette, Antoine Adenis, Mathieu Messager, Xavier Mirabel, Emmanuelle Tresch, Amaury Paumier, Véronique Vendrely, Laetitia Dahan, Olivier Glehen, Frederique Vasseur, Thomas Lacornerie, Guillaume Piessen, Farid El Hajbi, William B Robb, Stéphanie Clisant, Andrew Kramar, Christophe Mariette, Antoine Adenis

Abstract

Background: Often curative treatment for locally advanced resectable esophageal or gastro-esophageal junctional cancer consists of concurrent neoadjuvant radiotherapy and chemotherapy followed by surgery. Currently, one of the most commonly used chemotherapy regimens in this setting is a combination of a fluoropyrimidin and of a platinum analogue. Due to the promising results of the recent CROSS trial, another regimen combining paclitaxel and carboplatin is also widely used by European and American centers. No clinical study has shown the superiority of one treatment over the other. The objective of this Phase II study is to clarify clinical practice by comparing these two chemotherapy treatments. Our aim is to evaluate, in operable esophageal and gastro-esophageal junctional cancer, the complete resection rate and severe postoperative morbidity rate associated with these two neoadjuvant chemotherapeutic regimens (carboplatin-paclitaxel or fluorouracil-oxaliplatin-folinic acid) when each is combined with the radiation regime utilized in the CROSS trial.

Methods/design: PROTECT is a prospective, randomized, multicenter, open arms, phase II trial. Eligible patients will have a histologically confirmed adenocarcinoma or squamous cell carcinoma and be treated with neoadjuvant radiochemotherapy followed by surgery for stage IIB or stage III resectable esophageal cancer. A total of 106 patients will be randomized to receive either 3 cycles of FOLFOX combined to concurrent radiotherapy (41.4 Grays) or carboplatin and paclitaxel with the same radiation regimen, using a 1:1 allocation ratio.

Discussion: This ongoing trial offers the unique opportunity to compare two standards of chemotherapy delivered with a common regimen of preoperative radiation, in the setting of operable locally advanced esophageal or gastro-esophageal junctional tumors.

Trial registration: NCT02359968 (ClinicalTrials.gov) (registration date: 9 FEB 2015), EudraCT: 2014-000649-62 (registration date: 10 FEB 2014).

Keywords: Chemoradiotherapy; Esophageal cancer; FOLFOX; Paclitaxel-carboplatin; Randomized trial.

Figures

Fig. 1
Fig. 1
Study flow chart. R: randomization, cy: cycles, RT: radiotherapy, CarboP-pacliT: carboplatin-paclitaxel, FOLFOX: fluorouracil, leucovorin, oxaliplatin, *23 fractions of 1.8Gy, 5 fractions per week, starting the first day of the first cycle of chemotherapy

References

    1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:359–386. doi: 10.1002/ijc.29210.
    1. Mariette C, Piessen G, Briez N, Gronnier C, Triboulet JP. Esophagogastric junction adenocarcinoma: which therapeutic approach ? Lancet Oncol. 2011;12:296–305. doi: 10.1016/S1470-2045(10)70125-X.
    1. Sjoquist KM, Burmeister BH, Smithers BM, Zalcberg JR, Simes RJ, Barbour A, et al. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable esophageal carcinoma: an updated meta-analysis. Lancet Oncol. 2011;12:681–692. doi: 10.1016/S1470-2045(11)70142-5.
    1. Shapiro J, van Lanschot JJ, Hulshof MC, van Hagen P, van Berge Henegouwen MI, Wijnhoven BP, et al. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol. 2015;5(15):40–46.
    1. van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen MI, Wijnhoven BP, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;336:2074–2084. doi: 10.1056/NEJMoa1112088.
    1. Mariette C, Robb WB, Piessen G, Adenis A. Neoadjuvant chemoradiation in esophageal cancer. Lancet Oncol. 2015;S1470:127–128.
    1. Sobin LH, Gospodarowicz MK, Wittekind C. TNM classification of malignant tumors. 7. Oxford: Wiley-Blackwell; 2010.
    1. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240:205–213. doi: 10.1097/.
    1. Mandard AM, Dalibard F, Mandard JC, Marnay J, Henry-Amar M, Petiot JF, et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer. 1994;73:2680–2686. doi: 10.1002/1097-0142(19940601)73:11<2680::AID-CNCR2820731105>;2-C.
    1. Briez N, Piessen G, Bonnetain F, Brigand C, Carrere N, Collet D, et al. Open versus laparoscopically-assisted esophagectomy for cancer: a multicentre randomised controlled phase III trial - the MIRO trial. BMC Cancer. 2011;11:310. doi: 10.1186/1471-2407-11-310.
    1. Mariette C, Robb WB. Piessen G Quality criteria for esophageal and gastresophageal junction cancer surgery. Oncologie. 2013;5:133–138. doi: 10.1007/s10269-013-2264-z.
    1. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumors: revised RECIST guideline (version 1.1) Eur J Cancer. 2009;45:228–247. doi: 10.1016/j.ejca.2008.10.026.
    1. Conroy T, Galais MP, Raoul JL, Bouché O, Gourgou-Bourgade S, Douillard JY, et al. Definitive chemoradiotherapy with FOLFOX versus fluorouracil and cisplatin in patients with esophageal cancer (PRODIGE5/ACCORD17): final results of a randomized phase 2/3 trial. Lancet Oncol. 2014;15:305–314. doi: 10.1016/S1470-2045(14)70028-2.
    1. Starling N, Rao S, Cunningham D, Iveson T, Nicolson M, Coxon F, et al. Thromboembolism in patients with advanced gastresophageal cancer treated with anthracycline, platinum, and fluoropyrimidine combination chemotherapy: a report from the UK National Cancer Research Institute Upper Gastrointestinal Clinical Studies Group. J Clin Oncol. 2009;27:3786–3793. doi: 10.1200/JCO.2008.19.4274.
    1. Wang SL, Liao Z, Vaporciyan AA, Tucker SL, Liu H, Wei X, et al. Investigation of clinical and dosimetric factors associated with postoperative pulmonary complications in esophageal cancer patients treated with concurrent chemoradiotherapy followed by surgery. Int J Radiat Oncol Biol Phys. 2006;64:692–699. doi: 10.1016/j.ijrobp.2005.08.002.
    1. Asakura H, Hashimoto T, Zenda S, Harada H, Hirakawa K, Mizumoto M, et al. Analysis of dose- volume histogram parameters for radiation pneumonitis after definitive concurrent chemoradiotherapy for esophageal cancer. Radiother Oncol. 2010;95:240–244. doi: 10.1016/j.radonc.2010.02.006.
    1. McCurdy M, McAleer MF, Wei W, Ezhil M, Johnson V, Khan M, et al. Induction and concurrent taxanes enhance both the pulmonary metabolic radiation response and the radiation pneumonitis response in patients with esophagus cancer. Int J Radiat Oncol Biol Phys. 2010;76:816–823. doi: 10.1016/j.ijrobp.2009.02.059.
    1. Adenis A, Mirabel X, Mariette X. Is preoperative chemoradiation with paclitaxel and carboplatin a new standard of treatment for esophageal cancer. Int J Radiat Oncol Biol Phys. 2013;86:16–17. doi: 10.1016/j.ijrobp.2012.11.021.

Source: PubMed

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit