Irinotecan plus S-1 versus S-1 in patients with previously treated recurrent or metastatic esophageal cancer (ESWN 01): a prospective randomized, multicenter, open-labeled phase 3 trial.

Abstract

BACKGROUND:

The benefit of systemic treatments in esophageal squamous cell carcinoma (ESCC) which has progressed after chemotherapy is still uncertain and optimal regimens based on randomized trials have not yet been established. We aimed to compare the efficacy of irinotecan plus S-1 with S-1 monotherapy in recurrent or metastatic ESCC patients who had resistance to platinum- or taxane-based chemotherapy.

METHODS:

We conducted a prospective randomized, multicenter, open-label, phase 3 trial in 15 centers across China. Eligible patients were adults with histologically confirmed recurrent or metastatic ESCC, and were randomly assigned (ratio, 1:1) to receive either irinotecan plus S-1 (intravenous infusion of irinotecan [160 mg/m2] on day 1 and oral S-1 [80-120 mg] on days 1-10, repeated every 14 days) or oral S-1 monotherapy (80-120 mg/day on days 1-14, repeated every 21 days) using a central computerized minimization procedure. The primary endpoint was progression-free survival (PFS).

RESULTS:

Between December 23, 2014 and July 25, 2016, we screened 148 patients and randomly assigned 123 patients to receive either irinotecan plus S-1 regimen (n = 61) or S-1 monotherapy (n = 62). After a median follow-up of 29.2 months (95% confidence interval [CI] 17.5-40.9 months), the median PFS was significantly longer in the irinotecan plus S-1 group than in the S-1 monotherapy group (3.8 months [95% CI 2.9-4.3 months] vs. 1.7 months [95% CI 1.4-2.7 months], hazard ratio = 0.58, 95% CI 0.38-0.86, P = 0.006). The objective response rates were 24.6% in the irinotecan plus S-1 group and 9.7% in the S-1 monotherapy group (P = 0.002). The patients in the irinotecan plus S-1 group presented with increased rates of grade 3-4 leukopenia (16.4% vs. 0%), neutropenia (14.8% vs. 1.6%), and nausea (4.9% vs. 0%). No significant difference in grade 3-4 diarrhea and no treatment-related deaths were observed in both groups.

CONCLUSIONS:

The combination of irinotecan with S-1 was similarly tolerable but significantly prolonged PFS compared to S-1 monotherapy as a second- or third-line treatment in patients with recurrent or metastatic ESCC. Clinical Trial Registration NCT02319187. Registered on December 9, 2014.

• Authors: Jing Huang, Binghe Xu, Ying Liu, Junxing Huang, Ping Lu, Yi Ba, Lin Wu, Yuxian Bai, Shu Zhang, Jifeng Feng, Ying Cheng, Jie Li, Lu Wen, Xianglin Yuan, Changwu Ma, Chunhong Hu, Qingxia Fan, Xi Wang
• Journal: Cancer communications (London, England) (Cancer Commun (Lond)) Vol. 39 Issue 1 Pg. 16 (04 02 2019) ISSN: 2523-3548 [Electronic] United States
• PMID: 30940189 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites, Antineoplastic
• Drug Combinations
• Topoisomerase I Inhibitors
• S 1 (combination)
• Tegafur
• Oxonic Acid
• Irinotecan

Topics

• Adult
• Aged
• Antimetabolites, Antineoplastic (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Disease-Free Survival
• Drug Combinations
• Esophageal Neoplasms (drug therapy, pathology)
• Esophageal Squamous Cell Carcinoma (drug therapy, pathology)
• Female
• Humans
• Infusions, Intravenous
• Irinotecan (therapeutic use)
• Male
• Middle Aged
• Neoplasm Recurrence, Local (drug therapy, pathology)
• Oxonic Acid (therapeutic use)
• Tegafur (therapeutic use)
• Topoisomerase I Inhibitors (therapeutic use)