Randomized study of the clinical effects of ω-3 fatty acid–containing enteral nutrition support during neoadjuvant chemotherapy on chemotherapy-related toxicity in patients with esophageal cancer

Highlights

• Little is known about the effect of ω-3 fatty acids on reducing chemotherapy-related toxicities.

• A randomized study was conducted to compare ω-3–rich enteral nutrition (EN) with ω-3–poor EN in patients undergoing cisplatin-based chemotherapy.

• ω-3–rich EN reduced the incidence of chemotherapy-related mucosal toxicities and had a hepatoprotective effect during chemotherapy.

Abstract

Objectives

Omega-3 (ω-3) fatty acids have potential positive effects during chemotherapy, such as body weight maintenance and muscle mass preservation. However, little is known about the effect this supplement might have on reducing chemotherapy-induced toxicities. The aim of this study was to determine the usefulness of ω-3 fatty acid supplementation in the reduction of chemotherapy-related toxicities.

Methods

Sixty-one patients undergoing neoadjuvant chemotherapy for esophageal cancer randomly received ω-3–rich enteral nutrition (EN; n = 31) or ω-3–poor EN support (n = 30) for 15 d during chemotherapy. The daily dosage of ω-3 fatty acids was 900 mg in the ω-3–rich group and 250 mg in the ω-3–poor group. The primary endpoint was the frequency of grade 3/4 neutropenia, and secondary endpoints included other chemotherapy-related adverse events, body weight, and inflammatory markers.

Results

The total and dietary intake calories during chemotherapy were equal in both groups. There was no significant difference in the body weight change after chemotherapy between the two groups. There was no significant difference in the incidence of grade 3/4 leukopenia and neutropenia (P > 0.05). However, stomatitis was significantly less frequent in the ω-3–rich group, than in the ω-3–poor group (P = 0.018). Grade 3/4 diarrhea occurred relatively less frequently in the ω-3–rich group than in the ω-3–poor group; however, this difference was not significant (16.1% versus 36.7%, respectively, P = 0.068). Increases in the aspartate aminotransferase and alanine aminotransferase levels were seen significantly less frequently in the ω-3–rich group than in the ω-3–poor group (P = 0.012 and P = 0.015, respectively).

Conclusions

ω-3–rich EN support decreased the frequency of chemotherapy-induced mucosal toxicities, such as stomatitis and diarrhea, and exhibited a hepatoprotective effect during chemotherapy, compared with the ω-3–poor EN support.

Introduction

Chemotherapy-related toxicity is a major obstacle to the successful treatment of advanced cancers. The most common chemotherapy-related toxicities include leukopenia, anemia, general fatigue, stomatitis, and appetite loss. These toxicities not only reduce patient quality of life, but may sometimes lead to the discontinuation of treatment and the dose reduction of anticancer drugs, which in turn may attenuate the effectiveness of chemotherapy [1], [2]. Any approach aimed at reducing chemotherapy-induced toxicities is needed to maximize the efficacy of treatment.

A randomized study was previously completed that compared the effects of enteral nutrition (EN) support with parenteral nutrition (PN) support on chemotherapy-induced toxicities in patients with thoracic esophageal cancer who underwent neoadjuvant chemotherapy [3]. The finding demonstrated that EN support markedly decreased the frequency of grade 3/4 hematologic adverse events (AEs) including leukopenia and neutropenia. However, the mechanism by which EN support decreased the incidence of hematologic AEs could not be fully explained. One potential explanation is that ω-3 fatty acids, which were abundantly present in the nutritional supplement used in the previous study, may have had a positive effect on decreasing the frequency of grade 3/4 hematologic AEs. ω-3 fatty acid supplementation in patients undergoing chemotherapy, radiotherapy, or both may help maintain body weight and preserve body composition [4], [5], [6]. However, little is known regarding the effect of ω-3 fatty acids in patients undergoing chemotherapy, especially with regard to the reduction of chemotherapy-induced toxicities. Thus, additional clinical trials were required to determine the effect of ω-3 fatty acids on chemotherapy-related toxicities.

The present clinical trial was designed to determine the usefulness of ω-3 fatty acid supplementation in the reduction of chemotherapy-related toxicities. We conducted a prospective, randomized study that compared EN containing abundant amounts of ω-3 fatty acids with EN containing a scarce amount of ω-3 fatty acids in patients with esophageal cancer who received neoadjuvant chemotherapy.