Single-Agent Versus Double-Agent Chemotherapy in Concurrent Chemoradiotherapy for Esophageal Squamous Cell Carcinoma: Prospective, Randomized, Multicenter Phase II Clinical Trial

Zhenhuan Zhao, Yixue Wen, Dongbiao Liao, Jidong Miao, Yan Gui, Hongwei Cai, Yang Chen, Min Wei, Qiang Jia, Honggang Tian, Mingqiang Sun, Yu Zhang, Gang Feng, Xiaobo Du, Zhenhuan Zhao, Yixue Wen, Dongbiao Liao, Jidong Miao, Yan Gui, Hongwei Cai, Yang Chen, Min Wei, Qiang Jia, Honggang Tian, Mingqiang Sun, Yu Zhang, Gang Feng, Xiaobo Du

Abstract

Lessons learned: The efficacy of single-agent chemotherapy was not significantly different from that of double-agent chemotherapy in concurrent chemoradiotherapy for inoperable esophageal squamous cell carcinoma. Single-agent concurrent chemoradiotherapy had lower gastrointestinal and hematologic toxicity. Overall survival and progression-free survival were not significantly different between single- and double-agent concurrent chemoradiotherapy.

Background: This multicenter, randomized, phase II trial aimed to compare the efficacy and safety of single-agent concurrent chemoradiotherapy using the oral fluoropyrimidine S-1 with those of double-agent concurrent chemoradiotherapy using S-1 and cisplatin in patients with inoperable esophageal squamous cell carcinoma.

Methods: Patients with inoperable esophageal squamous cell carcinoma (clinical stages I to III) were randomly allocated to the single-agent group (S-1) or the double-agent group (S-1/cisplatin). The concurrent intensity-modulated radiation therapy plan was similar for both groups: planning target volume 1.8 Gy/f*30-33f and planning gross target volume of 2 Gy/f*30-33f. The primary outcome measure was the endoscopic complete response rate.

Results: Of the 105 patients randomized, 89 were assessable. The endoscopic complete response rate was 46.9% (23/49) in the single-agent group and 52.5% (21/40) in double-agent group. The median progression-free survival within a median follow-up of 23 months was 20 and 21 months, respectively. The median overall survival was 26 months and not reached, respectively. Grade 3 hematological toxicities occurred in 4.1% and 27.5% of the patients in the single- and the double-agent group, respectively.

Conclusion: Single-agent chemotherapy in concurrent chemoradiotherapy for inoperable esophageal squamous cell carcinoma has good efficacy and safety, thus warranting a phase III trial.

Trial registration: ClinicalTrials.gov NCT02913066.

Keywords: Chemoradiotherapy; Cisplatin; Esophageal cancer; Esophageal squamous cell carcinoma; Fluoropyrimidine S-1; Lymphopenia.

© 2020 The Authors. The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.

Figures

Figure 1
Figure 1
Kaplan‐Meier analysis of overall survival (OS). The median follow‐up period was 23 months. There was no significant difference in OS (median, 26 months vs. not reached; p = .367) between the single‐agent group and the double‐agent group.

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