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

Abstract

BackgroundOften 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/designPROTECT 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.DiscussionThis 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 registrationNCT02359968 (ClinicalTrials.gov) (registration date: 9 FEB 2015), EudraCT: 2014-000649-62 (registration date: 10 FEB 2014)

Surgical treatment of esophageal cancer in the era of multimodality management

“…The NEOSCOPE study investigates whether induction chemotherapy followed by either oxaliplatin/capecitabine or paclitaxel/carboplatin, both combined with 45 Gy radiation, is superior as preoperative regimen in pathological complete response of resectable esophageal adenocarcinoma . Finally, the PROTECT‐1402 study compares three cycles of FOLFOX combined with concurrent radiotherapy (41.4 Gy) or carboplatin and paclitaxel with the same radiation regimen for esophageal and junctional cancer . An overview of these studies (including http://ClinicalTrials.gov identifiers) is presented in Table .…”

“…40 Finally, the PROTECT-1402 study compares three cycles of FOLFOX combined with concurrent radiotherapy (41.4 Gy) or carboplatin and paclitaxel with the same radiation regimen for esophageal and junctional cancer. 41 An overview of these studies (including ClinicalTrials.gov identifiers) is presented in Table 1.…”

Neoadjuvant treatment strategy for locally advanced thoracic esophageal cancer

“…In the setting of definitive CRT, the PRODIGE5/ACCORD17 trial showed that the use of oxaliplatin is safer and more convenient, with fewer cases of sudden death, than cisplatin . The PROTECT trial is an ongoing randomized phase II trial comparing two NACRT regimens (CROSS vs FOLFOX) in resectable esophageal and EGJ cancers of SCC or AC …”

Neoadjuvant treatment of locally advanced esophageal and junctional cancer: the evidence-base, current key questions and clinical trials

“…It is a "pick a winner" design based on pCR,, with 38 patients with esophageal or junctional adenocarcinoma (AEG type I/II; ≥T3±≥N1) per treatment arm, the trial will be used to define the optimal regimen for a future phase III trial comparing neoadjuvant chemotherapy. Similarly, the PROTECT-1402 French trial (NCT02359968) is a phase II trial which will randomise 106 patients with stage II or III esophageal adenocarcinoma or squamous cell carcinoma to one of two neoadjuvant chemotherapy regimens with standard concurrent 41.4 Gy radiation (27). The chemo regimens are 3 cycles of FOLFOX or carboplatin/ paclitaxel.…”