1425MO - Effects of elemental diet for gastrointestinal adverse events in patients with esophageal cancer receiving docetaxel/cisplatin/5-fluorouracil (EPOC 2 study: JFMC49-1601-C5): A phase III randomized controlled trial

Background

Oral mucositis (OM) is an unpleasant adverse event in cancer patients receiving chemotherapy. A prospective multicenter feasibility study, EPOC study, has shown that an elemental diet (ED) may prevent OM determined by special diagnostic tools. In that study, we established a central review system (CRS) to assess the oral environment. OM grades were rated by a dental oncology specialist blinded to background data. Further evaluation as phase III randomized controlled trial (RCT) was needed.

Methods

We conducted a phase III multicenter RCT to elucidate the preventive effect of ED against OM in patients with esophageal cancer (EC) receiving DCF (docetaxel, cisplatin, and 5-fluorouracil) therapy. Patients were randomly assigned to receive two cycles of DCF with (group A) or without (group B) ED (160 g/day) at a 1:1 ratio. The primary endpoint was the incidence of grade ≥ 2 OM assessed using CRS by two judges. Secondary endpoints were changes in body weight, prealbumin, c-reactive protein (CRP), rate of grade ≥ 2 OM, and DCF completion rate based on ED compliance.

Results

117 patients were enrolled and randomized; 4 failed to start treatment and were excluded from primary analysis; 55 and 58 patients were allocated to groups A and B, respectively. There was no significant difference in patients’ background. Grade ≥ 2 OM was demonstrated by 8 (14.5%) and 20 (34.5%) patients in groups A and B, respectively (p = 0.0141). At day 57, changes in body weight and prealbumin (%) were significantly higher in group A than group B (p = 0.0139 and 0.0181, respectively). During chemotherapy, changes in CRP (%) were lower in group A than group B, especially at day 36 (p =0.0394); patients with 100% ED compliance presented 13.3% of grade ≥ 2 OM, increased to 20% in those failing 100% compliance (p = 0.6273). DCF completion rate was 100% in patients with 100% ED compliance and 70% in patients failing ED completion (p = 0.0046).

Conclusions

Our multi-institutional RCT shows that ED has a preventive effect on OM in patients with EC receiving chemotherapy.

Clinical trial identification

jRCT s071180029.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Japanese Foundation for Multidisciplinary Treatment of Cancer and EA Pharma Co., Ltd.

Disclosure

E. Otsuji: Research grant/Funding (institution), Endowed chair: Yakult Honsha Co., Ltd.. H. Baba: Research grant/Funding (institution): Yakult Honsha Co.,Ltd.. S. Morita: Honoraria (self): Bristol-Myers Squibb Company. Y. Kitagawa: Advisory/Consultancy: Ono Pharmaceutical Co., Ltd.; Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Taiho Pharmaceutical Co., Ltd; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Chugai Pharmaceutical Co., Ltd; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Yakult Honsha Co. Ltd.; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Daiichi Sankyo Company, Limited; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Merck Serono Co., Ltd; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): AsahiKASEI Co., Ltd.; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): EA Pharma Co., Ltd; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Otsuka Pharmaceutical Co., Ltd; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Takeda Pharmaceutical Co., Ltd; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Otsuka Pharmaceutical Factory Inc.; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Shionogi & Co., Ltd; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Kaken Pharmaceutical Co.,Ltd.; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Astellas Pharma Inc.; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Medicon Inc; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Dainippon Sumitomo Pharma Co., Ltd.; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Taisho Toyama Pharmaceutical Co., Ltd.; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Kyouwa Hakkou Kirin Co., Ltd.; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Ono Pharmaceutical Co., Ltd.; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Nihon Pharmaceutical Co., Ltd.; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Japan Blood Products Organization; Speaker Bureau/Expert testimony, Research grant/Funding (self): Sanofi K.K.; Honoraria (self), Speaker Bureau/Expert testimony: Eisai Co., Ltd.; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (self): Tsumura & Co.; Research grant/Funding (self): Kowa Pharmaceutical Co., Ltd.; Research grant/Funding (self): Pfizer Japan Inc.; Research grant/Funding (self): Medtronic Japan Co., Ltd.; Research grant/Funding (self): Abbott Japan Co., Ltd; Research grant/Funding (self): Fujifilm Toyama Chemical Co., Ltd. K. Yoshida: Research grant/Funding (self): Sanofi K.K.; Research grant/Funding (self), no involvement in intellectual property: Yakult Honsha Co.,Ltd. All other authors have declared no conflicts of interest.