A randomized trial of sodium alginate prevention of radiation-induced esophagitis in patients with locally advanced NSCLC receiving concurrent chemoradiotherapy: OLCSG1401

Abstract

Abstract Background Sodium alginate, which has been approved for treatment of gastritis in Japan, is highly viscous and thus remains in the esophageal mucosa for long periods, leading to a protective effect in the esophagus. The purpose of this trial was to investigate whether sodium alginate has a substantial preventive effect on severe esophagitis in pts with non-small-cell lung cancer (NSCLC) receiving concurrent chemoradiotherapy (CRT). Methods Patients with untreated stage III NSCLC who were eligible for concurrent CRT were randomly assigned at a 1:1:1 ratio to receive one of the following treatments: sodium alginate administered concomitantly with CRT (A), sodium alginate administered soon after development of extremely mild esophagitis during CRT (B), or water administered with CRT (C). The primary endpoint was the proportion of pts with G3 or higher severe esophagitis (CTCAE ver. 4.0). Results Ninety-four patients were randomly assigned to the three treatment arms between Feb 2014 and Sep 2018. The study was prematurely terminated in Oct 2018 because of slow accrual. The proportion (95% confidence interval) of patients with G3 or more severe esophagitis was 12.5% (3.5–29.0%) in arm A, 9.8% (2.0–25.8%) in arm B, and 19.4% (7.5–37.5%) in arm C. Fewer patients receiving sodium alginate had onset of G3 esophagitis, but the differences compared with arm C were not significant (A v C: p\xa0=\xa00.46; B v C: p\xa0=\xa00.28). The rate of non-hematologic toxicities other than esophagitis was 29% in arm A, 26% in arm B, and 43% in arm C. Of note, early use (arm A) but not late use (arm B) of sodium alginate resulted in a significantly lower rate of febrile neutropenia (FN) compared with arm C (A v C: 3.1% v 19.4%, p\xa0=\xa00.04; B v C: 6.5% v 19.4%, p\xa0=\xa00.13). The 2-year progression-free and overall survival rates were 36% and 78% in arm A, 52% and 90% in arm B, and 61% and 75% in arm C, respectively. Conclusions Sodium alginate did not show a significant preventative effect on radiation-induced severe esophagitis in patients with NSCLC. However, its early use resulted in a lower rate of FN onset induced by CRT, suggesting that esophageal mucosal protection by sodium alginate may suppress FN. Clinical trial identification UMIN 000013113. Legal entity responsible for the study Okayama Lung Cancer Study Group. Funding Has not received any funding. Disclosure T. Yokoyama: Honoraria (self): Chugai Pharmaceutical co ltd; Honoraria (self): Nippon Boehringer Ingelheim; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): MSD KK; Honoraria (self): AstraZeneca; Honoraria (self): Ono Pharmaceutical co Ltd. K. Ninomiya: Honoraria (self): Lilly Japan; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): AstraZeneca; Honoraria (self): Ono Pharmaceutical co ltd; Honoraria (self): Chugai Pharmaceutical co ltd; Honoraria (self): Nippon Boehringer Ingelheim; Honoraria (self): MSD KK. A. Bessho: Honoraria (self), Research grant / Funding (self): AstraZeneca; Honoraria (self): Chugai Pharmaceutical; Honoraria (self), Research grant / Funding (self): Ono Pharmaceutical; Honoraria (self): Bristol-Myers Squibb Japan; Honoraria (self), Research grant / Funding (self): Pfizer; Honoraria (self): Nippon Boehringer Ingelheim; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Astellas Pharma; Honoraria (self): Novartis; Research grant / Funding (self): Kyorin; Research grant / Funding (self): Amgen; Research grant / Funding (self): Taisho Toyama Pharma; Research grant / Funding (self): Bayer Yakuhin. S. Hosokawa: Honoraria (self): Bristol-Myers Squibb Japan; Honoraria (self): Ono Pharmaceutical; Honoraria (self): AstraZeneca. T. Kozuki: Honoraria (self), Research grant / Funding (institution): Chugai Pharmaceutical; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Lilly Japan; Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb Japan; Honoraria (self): Kyowa Hakko Kirin; Honoraria (self): Nippon Boehringer Ingelheim; Honoraria (self): MSD KK; Research grant / Funding (institution): Merck Serono. D. Harada: Honoraria (self): Ono Pharmaceutical; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Kyowa Hakko Kirin; Honoraria (self): AstraZeneca; Honoraria (self): Nippon Boehringer Ingelheim; Honoraria (self): MSD KK; Honoraria (self): Eli Lilly Japan. T. Murakami: Honoraria (self): Nippon Boehringer Ingelheim; Honoraria (self): AstraZeneca. N. Takigawa: Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Daiichi-Sankyo Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Chugai Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Taiho Pharmaceutical; Honoraria (self): Pfizer; Honoraria (self), Research grant / Funding (institution): Nippon Boehringer-Ingelheim; Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical; Honoraria (self): MSD KK; Honoraria (self), Research grant / Funding (institution): Eli Lilly Japan; Research grant / Funding (institution): Kyowa Hakko Kirin; Research grant / Funding (institution): Nippon Kayaku. K. Hotta: Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Nippon Boehringer Ingelheim; Honoraria (self): Nippon Kayaku; Honoraria (self): Taiho Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Chugai Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Novartis; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb Japan; Honoraria (self), Research grant / Funding (institution): Lilly Japan; Honoraria (self), Research grant / Funding (institution): MSD KK; Research grant / Funding (institution): Astellas Pharma. K. Kiura: Honoraria (self), Research grant / Funding (institution): Taiho Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self): Nippon Boehringer Ingelheim; Honoraria (self): Nippon Kayaku; Honoraria (self): Daiichi Sankyo; Honoraria (self): Shionogi; Honoraria (self), Research grant / Funding (institution): Chugai Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Novartis; Honoraria (self), Research grant / Funding (institution): Lilly Japan. All other authors have declared no conflicts of interest.