TY - JOUR
T1 - Effects of an elemental diet to reduce adverse events in patients with esophageal cancer receiving docetaxel/cisplatin/5-fluorouracil
T2 - a phase III randomized controlled trial—EPOC 2 (JFMC49-1601-C5)
AU - Tanaka, Y.
AU - Takeuchi, H.
AU - Nakashima, Y.
AU - Nagano, H.
AU - Ueno, T.
AU - Tomizuka, K.
AU - Morita, S.
AU - Emi, Y.
AU - Hamai, Y.
AU - Hihara, J.
AU - Saeki, H.
AU - Oki, E.
AU - Kunisaki, C.
AU - Otsuji, E.
AU - Baba, H.
AU - Matsubara, H.
AU - Maehara, Y.
AU - Kitagawa, Y.
AU - Yoshida, K.
N1 - Funding Information:
We thank all patients and their families who participated in this study, and all the physicians, nurses, pharmacists, and study coordinators who enabled the conduct of this research. We would also like to thank the Japanese Foundation for Multidisciplinary Treatment of Cancer teams and medical advisers; Drs M. Kitajima and S. Saji and the independent data monitoring committee; Drs Y. Emi, J. Sakamoto, and A. Tsuji and the statistical analysts; and Dr S. Morita. Finally, we also acknowledge English editing services provided by Dr Sally-Anne Mitchell of Edanz (www.edanz.com). This work was supported by EA Pharma Co. Ltd. EA Pharma Co. Ltd was not involved in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the article for publication. YT, HT, YN, and HN have declared no conflicts of interest. TU reports non-financial support and other support from The Japanese Foundation for Multidisciplinary Treatment of Cancer, during the conduct of the study; and personal fees from Maruho Co. Ltd, Meiji Seika Pharma Co. Ltd, and Otsuka Pharmaceutical Co. Ltd, outside the submitted work. KT has declared no conflicts of interest. SM reports personal fees from Bristol-Myers Squibb Company outside the submitted work. YE, YH, and JH have declared no conflicts of interest. HS reports personal fees from Ono Pharmaceutical Co. Ltd and Bristol-Myers Squibb Company; and grants from Taiho Pharmaceutical Co. Ltd and Chugai Pharmaceutical Co. Ltd, outside the submitted work. EO reports other support from Chugai Pharmaceutical Co. Ltd, Merck Biopharm Co. Ltd, Eli Lilly Japan K.K. Takeda Pharmaceutical Co. Ltd, Taiho Pharmaceutical Co. Ltd, and Bayer, outside the submitted work. CK has declared no conflicts of interest. EO reports grants from SBI Pharmaceuticals Co. Ltd, Takeda Pharmaceutical Co. Ltd, and Johnson & Johnson K.K.; grants and other support from Taiho Pharmaceutical Co. Ltd; and other support from Yakult Honsha Co. Ltd and Chugai Pharmaceutical Co. Ltd, outside the submitted work. HB reports personal fees from Eli Lilly Japan K.K.; grants and personal fees from Taiho Pharmaceutical Co, Ltd and Ono Pharmaceutical Co. Ltd; and grants from Merck Biopharma Co. Ltd and MSD K.K. outside the submitted work. HM and YM have declared no conflicts of interest. YK reports grants and personal fees from EA Pharma Co. Ltd, during the conduct of the study; grants and personal fees from Asahi Kasei Pharma Corporation, Taiho Pharmaceutical Co. Ltd, Chugai Pharmaceutical Co. Ltd, EA Pharma Co. Ltd, Yakult Honsha Co. Ltd, Otsuka Pharmaceutical Co. Ltd, Otsuka Pharmaceutical Factory Inc. Shionogi & Co. Ltd, Kaken Pharmaceutical Co. Ltd, Astellas Pharma Inc. Dainippon Sumitomo Pharma, Ono Pharmaceutical Co. Ltd, Nihon Pharmaceutical Co. Ltd, and Eisai Co. Ltd; and personal fees from Taisho Toyama Pharmaceutical Co. Ltd, Shionogi & Co. Ltd, Sanofi K.K. Kowa Pharmaceutical Co. Ltd, Medicon Inc. Kyowa Hakko Kirin Co. Ltd, Eisai Co. Ltd, Tsumura & Co. Fujifilm Toyama Chemical Co. Ltd, Covidien Japan Inc. Takeda Pharmaceutical Co. Ltd, and Teijin Pharma Ltd, outside the submitted work. KY reports grants and personal fees from Nippon Kayaku, Sanofi K.K. and Yakult Honsha Co. Ltd; grants from Kyowa Kirin; and personal fees from Bristol-Myers Squibb Japan, EA Pharma Co. Ltd, and Pfizer, during the conduct of the study; grants and personal fees from Asahi Kasei Pharma Corporation, Chugai Pharmaceutical Co. Ltd, Covidien Japan Inc. Daiichi Sankyo, Eli Lilly Japan K.K. Johnson & Johnson, Merck Serono, MSD K.K. Novartis, Ono Pharmaceutical Co. Ltd, Taiho Pharmaceutical Co, Ltd, Takeda Pharmaceutical Co. Ltd, and Tsumura & Co.; grants from Abbott, AbbVie, Astellas, Biogen Japan, Celgene, Eisai, GlaxoSmithKline K.K. Kaken Pharmaceutical Co. Ltd, KCI, Meiji Seika Pharma Co. Ltd, Otsuka Pharm, Koninklijke Philips, and Toray Medical; and personal fees from AstraZeneca, Denka Co. Ltd, Olympus, Sanwa Kagaku Kenkyusho, SBI Pharma, Teijin Pharma Ltd, and Terumo, outside the submitted work. The data sources for this study will not be shared.
Funding Information:
This work was supported by EA Pharma Co., Ltd. EA Pharma Co., Ltd was not involved in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the article for publication.
Publisher Copyright:
© 2021 The Authors
PY - 2021/10
Y1 - 2021/10
N2 - Background: Oral mucositis (OM) is an unpleasant adverse event in patients receiving chemotherapy. A prospective feasibility study showed that elemental diet (ED), an oral supplement that does not require digestion, may prevent OM. Based on this, we established a central review system for oral cavity assessment by dental oncology specialists blinded to background data. We used this system to elucidate the preventive effect of an ED against OM in patients with esophageal cancer receiving docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy. Patients and methods: In this phase III, multicenter, parallel-group, controlled trial, patients consuming a normal diet orally were randomly assigned (1: 1) to receive two cycles of DCF with (group A) or without (group B) an ED (Elental® 160 g/day). We assessed the incidence of grade ≥2 OM evaluated by two reviewers, changes in body weight, prealbumin, C-reactive protein, and DCF completion rate based on ED compliance. Results: Of the 117 patients randomly assigned to treatment, four failed to start treatment and were excluded from the primary analysis; thus, groups A and B comprised 55 and 58 patients, respectively. There were no significant differences in background characteristics. Grade ≥2 OM was observed in eight (15%) and 20 (34%) patients in groups A and B, respectively (P = 0.0141). Changes in body weight and prealbumin during the two DCF cycles were significantly higher in group A than B (P = 0.0022 and 0.0203, respectively). During the first cycle, changes in C-reactive protein were significantly lower in group A than B (P = 0.0338). In group A (receiving ED), the DCF completion rate was 100% in patients with 100% ED compliance and 70% in patients failing ED completion (P = 0.0046). Conclusions: The study findings demonstrate that an ED can prevent OM in patients with esophageal cancer receiving chemotherapy.
AB - Background: Oral mucositis (OM) is an unpleasant adverse event in patients receiving chemotherapy. A prospective feasibility study showed that elemental diet (ED), an oral supplement that does not require digestion, may prevent OM. Based on this, we established a central review system for oral cavity assessment by dental oncology specialists blinded to background data. We used this system to elucidate the preventive effect of an ED against OM in patients with esophageal cancer receiving docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy. Patients and methods: In this phase III, multicenter, parallel-group, controlled trial, patients consuming a normal diet orally were randomly assigned (1: 1) to receive two cycles of DCF with (group A) or without (group B) an ED (Elental® 160 g/day). We assessed the incidence of grade ≥2 OM evaluated by two reviewers, changes in body weight, prealbumin, C-reactive protein, and DCF completion rate based on ED compliance. Results: Of the 117 patients randomly assigned to treatment, four failed to start treatment and were excluded from the primary analysis; thus, groups A and B comprised 55 and 58 patients, respectively. There were no significant differences in background characteristics. Grade ≥2 OM was observed in eight (15%) and 20 (34%) patients in groups A and B, respectively (P = 0.0141). Changes in body weight and prealbumin during the two DCF cycles were significantly higher in group A than B (P = 0.0022 and 0.0203, respectively). During the first cycle, changes in C-reactive protein were significantly lower in group A than B (P = 0.0338). In group A (receiving ED), the DCF completion rate was 100% in patients with 100% ED compliance and 70% in patients failing ED completion (P = 0.0046). Conclusions: The study findings demonstrate that an ED can prevent OM in patients with esophageal cancer receiving chemotherapy.
KW - central review system
KW - chemotherapy
KW - elemental diet
KW - esophageal cancer
KW - oral mucositis
UR - http://www.scopus.com/inward/record.url?scp=85120317005&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85120317005&partnerID=8YFLogxK
U2 - 10.1016/j.esmoop.2021.100277
DO - 10.1016/j.esmoop.2021.100277
M3 - Article
C2 - 34626918
AN - SCOPUS:85120317005
SN - 2059-7029
VL - 6
JO - ESMO Open
JF - ESMO Open
IS - 5
M1 - 100277
ER -
