title: Three-Arm Randomized Trial of Sodium Alginate for Preventing Radiation-Induced Esophagitis in Locally Advanced Non-Small Cell Lung Cancer Receiving Concurrent Chemoradiotherapy: The OLCSG1401 Study Protocol.
abstract: Concurrent chemoradiotherapy (CRT) is the standard of care for locally advanced non-small cell lung cancer (LA-NSCLC). However, this intensive therapy often causes severe esophagitis, which could deteriorate a patient's quality of life (QOL), leading to poor treatment compliance. Sodium alginate, approved in Japan for gastritis, is sufficiently highly viscous to remain in the esophageal mucosa, providing a protective effect in the esophagus. To investigate whether this compound has a preventive effect against severe esophagitis in patients receiving concurrent CRT, we plan a 3-arm randomized trial of sodium alginate with 2 different schedules versus water. The primary endpoint is set as the proportion of patients with grade ≥ 3 esophagitis using the Common Terminology Criteria for Adverse Events, version 4.0. With stratification by institute, performance status, and percentage of the esophageal volume receiving >35 Gy, the patients will be randomly assigned to 1 of the following groups: sodium alginate initiated concomitantly with CRT (group A), sodium alginate initiated soon after the development of extremely mild esophagitis during CRT (group B), or water administered throughout CRT (group C). Assuming that the proportion of grade ≥ 3 esophagitis would be 8% in groups A and B and 27% in group C, the required sample size would be 200 patients, with 70% power and 5% α. The secondary endpoints include QOL, the frequency of additional prescriptions of analgesics, treatment response, and survival. The results of the present study will clarify whether sodium alginate can prevent esophagitis in patients with LA-NSCLC undergoing CRT.
authors.affiliation: Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Kiichiro
authors.initials: K
authors.lastname: Ninomiya
authors.affiliation: Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. Electronic address: ichiha-e@md.okayama-u.ac.jp.
authors.forename: Eiki
authors.initials: E
authors.lastname: Ichihara
authors.affiliation: Center of Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Hotta
authors.affiliation: Department of Respiratory Medicine, Kurashiki Central Hospital, Okayama, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Sone
authors.affiliation: Department of Respiratory Medicine, Onomichi Municipal Hospital, Hiroshima, Japan.
authors.forename: Toshi
authors.initials: T
authors.lastname: Murakami
authors.affiliation: Department of Respiratory Medicine, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan.
authors.forename: Daijiro
authors.initials: D
authors.lastname: Harada
authors.affiliation: Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Aichi, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Oze
authors.affiliation: Center for Clinical Oncology, Okayama University Hospital, Okayama, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Kubo
authors.affiliation: Department of Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center, Okayama, Japan.
authors.forename: Hisaaki
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Department of Respiratory Medicine, Iwakuni Medical Center, Yamaguchi, Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Kuyama
authors.affiliation: Department of Medical Oncology, National Hospital Organization Yamaguchi-Ube Medical Center, Ube, Japan.
authors.forename: Daizo
authors.initials: D
authors.lastname: Kishino
authors.affiliation: Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital, Okayama, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Bessho
authors.affiliation: Department of Respiratory Medicine, Chugoku Central Hospital, Hiroshima, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Harita
authors.affiliation: Department of Proton Beam Therapy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Katsui
authors.affiliation: Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Mitsune
authors.initials: M
authors.lastname: Tanimoto
authors.affiliation: Department of Allergy and Respiratory Medicine, Okayama University Hospital, Okayama, Japan.
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kiura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000464:Alginates / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy / Q000009:adverse effects*; D004941:Esophagitis / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D020723:Glucuronic Acid / Q000627:therapeutic use; D006603:Hexuronic Acids / Q000627:therapeutic use; D006801:Humans; D007564:Japan; D008175:Lung Neoplasms / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D011832:Radiation Injuries / Q000188:drug therapy* / Q000209:etiology; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D011879:Radiotherapy Dosage; D055815:Young Adult
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D011837:Radiation-Protective Agents; D020723:Glucuronic Acid
keywords: CRT; Lung cancer; Radiation esophagitis; Sodium alginate; Supportive care