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A randomized trial of sodium alginate prevention of esophagitis in LA-NSCLC receiving chemoradiotherapy: OLCSG1401

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Abstract

Background

Radiation esophagitis is a critical adverse event that needs to be appropriately managed while administering thoracic irradiation. This trial aimed to investigate whether sodium alginate has preventative effects on esophagitis in patients 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: initial or late use of oral sodium alginate (arms A and B) or water as control (arm C). The primary endpoint was the proportion of patients developing G3 or worse esophagitis.

Results

Overall, 94 patients were randomly assigned between February 2014 and September 2018. The study was prematurely terminated because of slow accrual. The proportions of patients with G3 or worse esophagitis were 12.5%, 9.8%, and 19.4% in arms A, B, and C, respectively. Patients receiving sodium alginate had fewer onsets of G3 esophagitis; however, differences compared with arm C were not significant (A vs. C: p = 0.46; B vs. C: p = 0.28). The rates of grade 3 or worse non-hematologic toxicities besides esophagitis were 29%, 26%, and 43% in arms A, B, and C, respectively. Interestingly, compared with arm C, a low rate of febrile neutropenia was observed in arm A (3.1% vs. 19.4%: p = 0.04).

Conclusions

Sodium alginate did not show significant preventative effects on radiation-induced esophagitis in patients with NSCLC. The frequency of CRT-induced febrile neutropenia was lower in the early use sodium alginate arm.

Trial registration

ClinicalTrials.gov Identifier Registry number: UMIN000013133

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Data availability

N/A

Code availability

See the Material and methods section.

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Acknowledgements

The authors wish to acknowledge and thank the investigators, coordinators, and all others involved who have contributed to this study. We would like to thank Editage (www.editage.com) for English language editing.

Author information

Authors and Affiliations

  1. Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

    Kiichiro Ninomiya & Yoshinobu Maeda

  2. Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, Japan

    Toshihide Yokoyama, Tae Hata & Hiroshige Yoshioka

  3. Center of Innovative Clinical Medicine, Okayama University Hospital, 2-5-1, Shikata-cho, Okayama, 700-8558, Japan

    Katsuyuki Hotta

  4. Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan

    Isao Oze

  5. Department of Proton Beam Therapy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

    Kuniaki Katsui

  6. Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital, Okayama, Japan

    Akihiro Bessho & Shinobu Hosokawa

  7. Department of Respiratory Medicine, NHO Iwakuni Clinical Center, Iwakuni, Japan

    Shoichi Kuyama & Kenichiro Kudo

  8. Department of Thoracic oncology and Medicine, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan

    Toshiyuki Kozuki & Daijiro Harada

  9. Department of Respiratory Medicine, Chugoku Central Hospital, Fukuyama, Japan

    Masayuki Yasugi

  10. Department of Respiratory Medicine, Onomichi Municipal Hospital, Onomichi, Japan

    Toshi Murakami

  11. Department of Medical Oncology, National Hospital Organization Yamaguchi-Ube Medical Center, Ube, Japan

    Masamoto Nakanishi

  12. Department of General Internal Medicine 4, Kawasaki Medical School, Okayama, Japan

    Nagio Takigawa

  13. Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan

    Katsuyuki Kiura

Authors
  1. Kiichiro Ninomiya
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  2. Toshihide Yokoyama
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  3. Katsuyuki Hotta
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  4. Isao Oze
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  5. Kuniaki Katsui
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  6. Tae Hata
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  7. Hiroshige Yoshioka
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  8. Akihiro Bessho
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  9. Shinobu Hosokawa
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  10. Shoichi Kuyama
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  11. Kenichiro Kudo
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  12. Toshiyuki Kozuki
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  13. Daijiro Harada
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  14. Masayuki Yasugi
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  15. Toshi Murakami
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  16. Masamoto Nakanishi
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  17. Nagio Takigawa
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  18. Yoshinobu Maeda
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  19. Katsuyuki Kiura
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Consortia

on behalf of Okayama Lung Cancer Study Group

Contributions

Conception and design: Ninomiya K, Hotta K, Oze I, and Katsui K.

Data collection: Yokoyama T, Hata T, Yoshioka H, Bessho A, Hosokawa S, Kuyama S, Kudo K, Kozuki T, Harada D, Yasugi M, Murakami T, Nakanishi M, and Takigawa N.

Data analysis and interpretation: Ninomiya K, Hotta K, and Oze I.

Writing the paper: Ninomiya K, Hotta K, Oze I, and Katsui K.

Project administration and supervision: Maeda Y and Kiura K.

Approval of the manuscript: All the authors.

Corresponding author

Correspondence to Katsuyuki Hotta.

Ethics declarations

Ethics approval

The study protocol was approved by the Ethics Review Board at each participating trial site and conducted according to the Helsinki Declaration, and registered at Clinical Trials Registry (UMIN000013133). See the Materials and Methods section.

Consent to participate

All patients signed written informed consent prior to the initiation of any study interventions. See the Materials and Methods section.

Consent for publication

The publication for this study was described in the protocol in advance, and appropriate consent had been obtained from all patients.

Conflict of interest

The authors whose names are listed immediately below report the following details of affiliation or involvement in an organization or entity with a financial or non-financial interest in the subject matter or materials discussed in this manuscript.

KN has received honoraria outside the current work from AstraZeneca, MSD, BMS, Boehringer-Ingelheim, Chugai Pharmaceutical, Eli Lilly, Taiho Pharmaceutical and Ono Pharmaceutical. TY has received honoraria outside the current work from Chugai Pharmaceutical, Boehringer-Ingelheim, Taiho Pharmaceutical, MSD, AstraZeneca and Ono Pharmaceutical. KH has received honoraria outside the current work from Pfizer, Eli Lilly, AstraZeneca, BMS, Ono Pharmaceutical, MSD, Chugai Pharmaceutical, Nippon Kayaku, Taiho Pharmaceutical, Boehringer-Ingelheim, Novartis, Daiichi-Sankyo, and Kyorin. KH also has received research funding outside of the current work from Eli Lilly, AstraZeneca, BMS, MSD, Chugai Pharmaceutical, and Astellas. KK has received honoraria outside the current work from Daiichi-Sankyo, Eisai, Chugai Pharmaceutical, Bayer, MSD, Oncolys BioPharma, and AstraZeneca. KK belongs to the endowed course funded by Tsuyama Chuo Hospital. AB has received honoraria outside the current work from Boehringer Ingelheim, AstraZeneca, Pfizer, Chugai, Ono Pharmaceutical, BMS, Novartis, Kyorin, Daiichi Sankyo, and FUJIFILM Toyama. AB also has received research funding outside the current work from AstraZeneca, Pfizer, Ono Pharmaceutical, Kyorin, AbbVie and FUJIFILM Toyama. TK has received outside the current work from Chugai Pharmaceutical, AstraZeneca, Eli Lilly, Taiho Pharmaceutical, BMS, Ono Pharmaceutical, MSD, Pfizer, Kyowa Kirin, Boehringer Ingelheim, Nippon Kayaku, and Novartis. TK also has received research funding outside the current work from Chugai Pharmaceutical, AstraZeneca, Eli Lilly, Taiho Pharmaceutical, BMS, and Merck Biopharma. DH has received outside the current work from Ono Pharmaceutical, BMS, Kyowa Kirin, AstraZeneca, Boehringer Ingelheim, Eli Lilly, MSD, Taiho Pharmaceutical, and Chugai Pharmaceutical. DH also has received research funding outside the current work from BMS, AstraZeneca, Eli Lilly, MSD, Chugai Pharmaceutical, Novartis, Kissei Pharmaceutical, Takeda Pharmaceutical, and Pfizer. NT has received outside the current work from AstraZeneca, Daiichi-Sankyo, Chugai Pharmaceutical, Taiho Pharmaceutical, Pfizer, Boehringer Ingelheim, Ono Pharmaceutical, MSD, Eli Lilly, Eisai, and BMS. NT also has received research funding outside the current work from AstraZeneca, Daiichi-Sankyo, Chugai Pharmaceutical, Taiho Pharmaceutical, Pfizer, Boehringer Ingelheim, Ono Pharmaceutical, MSD, Eli Lilly, Kyowa Kirin, and Nippon Kayaku. YM has received honoraria outside the current work from Pfizer, Mundipharma, Kyowa Kirin, BMS, Chugai Pharmaceutical, and Celgene. YM also has received research funding outside the current work from Kyowa Kirin, BMS, Chugai Pharmaceutical, Eisai, and Nippon Shinyaku. KK has received research funding outside the current work from Ono Pharmaceutical, Boehringer Ingelheim, Taiho Pharmaceutical, Chugai Phamaceutical, and BMS. All the other authors declare no conflicts of interest regarding this study.

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Ninomiya, K., Yokoyama, T., Hotta, K. et al. A randomized trial of sodium alginate prevention of esophagitis in LA-NSCLC receiving chemoradiotherapy: OLCSG1401. Support Care Cancer 29, 5237–5244 (2021). https://doi.org/10.1007/s00520-021-06092-1

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