A multicenter prospective phase III clinical randomized study of simultaneous integrated boost intensity-modulated radiotherapy with or without concurrent chemotherapy in patients with esophageal cancer: 3JECROG P-02 study protocol.

Abstract

BACKGROUND:

Since the development of three-dimensional conformal radiotherapy and intensity-modulated radiotherapy (IMRT), no prospective study has investigated whether concurrent chemoradiotherapy (SIB-IMRT with 60 Gy) remains superior to radiotherapy (SIB-IMRT) alone for unresectable esophageal cancer (EC). Furthermore, the optimal therapeutic regimen for patients who cannot tolerate concurrent chemoradiotherapy is unclear. We recently completed a phase I/II radiation dose-escalation trial using simultaneous integrated boost (SIB), elective nodal irradiation, and concurrent chemotherapy for unresectable EC. We now intend to conduct a prospective, phase III, randomized study of SIB-IMRT with or without concurrent chemotherapy. We aim to find a safe, practical, and effective therapeutic regimen to replace the conventional segmentation (1.8-2.0 Gy) treatment mode (radiotherapy ± chemotherapy) for unresectable EC.

METHODS:

This two-arm, open, randomized, multicenter, phase III trial will recruit esophageal squamous cell carcinoma patients (stage IIA-IVB [UICC 2002]; IVB only with metastasis to the supraclavicular or celiac lymph nodes). In all, 164 patients will be randomized using a 1:1 allocation ratio, and stratified by study site and disease stage, especially the extent of lymph node metastasis. Patients in the SIB arm will receive definitive SIB radiotherapy (95% planning target volume/planning gross tumor volume, 50.4 Gy/59.92 Gy/28 f, equivalent dose in 2-Gy fractions = 60.62 Gy). Patients in the SIB + concurrent chemotherapy arm will receive definitive SIB radiotherapy with weekly paclitaxel and a platinum-based drug (5-6 weeks). Four cycles of consolidated chemoradiotherapy will also be recommended. The primary objective is to compare the 1-year, 2-year, and 3-year overall survival of the SIB + chemotherapy group and SIB groups. Secondary objectives include progression-free survival, local recurrence-free rate, completion rate, and adverse events. Detailed radiotherapy protocol and quality-assurance procedures have been incorporated into this trial.

DISCUSSION:

In unresectable, locally advanced EC, a safe and effective total radiotherapy dose and reasonable segmentation doses are required for the clinical application of SIB-IMRT + two-drug chemotherapy. Whether this protocol will replace the standard treatment regimen will be prospectively investigated. The effects of SIB-IMRT in patients with poor physical condition who cannot tolerate definitive chemoradiotherapy will also be investigated.

TRIAL REGISTRATION:

clinicaltrials.gov ( NCT03308552 , November 1, 2017).

• Authors: Lin-Rui Gao, Xin Wang, Weiming Han, Wei Deng, Chen Li, Xiaomin Wang, Yidian Zhao, Wenjie Ni, Xiao Chang, Zongmei Zhou, Lei Deng, Wenqing Wang, Wenyang Liu, Jun Liang, Tao Zhang, Nan Bi, Jianyang Wang, Yirui Zhai, Qinfu Feng, Jima Lv, Ling Li, Zefen Xiao
• Journal: BMC cancer (BMC Cancer) Vol. 20 Issue 1 Pg. 901 (Sep 22 2020) ISSN: 1471-2407 [Electronic] England
• PMID: 32962674 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Organoplatinum Compounds
• Paclitaxel

Topics

• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Chemoradiotherapy
• Esophageal Neoplasms (diagnostic imaging, drug therapy, pathology, radiotherapy)
• Esophageal Squamous Cell Carcinoma (diagnostic imaging, drug therapy, pathology, radiotherapy)
• Female
• Humans
• Male
• Neoplasm Staging
• Organoplatinum Compounds (administration & dosage)
• Paclitaxel (administration & dosage)
• Prospective Studies
• Radiotherapy Planning, Computer-Assisted
• Radiotherapy, Intensity-Modulated