A phase III study evaluating oral glutamine and transforming growth factor-beta 2 on chemotherapy-induced toxicity in patients with digestive neoplasm

Dig Liver Dis. 2016 Mar;48(3):327-32. doi: 10.1016/j.dld.2015.11.025. Epub 2015 Dec 15.

Abstract

Background: Patients with gastrointestinal (GI) cancer are exposed to cachexia, which is highly correlated with chemotherapy-induced side effects. Research suggests that specific immunonutrients could prevent such toxicities.

Aims: The primary objective of this phase III study was to evaluate the efficacy of glutamine and transforming growth factor-β2 (TGF-β2) in the prevention of grade 3-4 non-hematological toxicities induced by chemotherapy in patients with GI cancer.

Patients and methods: We designed a double-blind, randomized, controlled and multicenter trial stratified according to center, type of chemotherapy, presence of cachexia, and age. Patients were randomized to receive either Clinutren Protect(®) (CP) or a control isocaloric diet (without TGF-β2 or glutamine).

Results: Between November 2007 and October 2011, 210 patients were enrolled in the study, of which 201 were included in the intention-to-treat analysis. Grade 3-4 non-hematological toxicities were not significantly different between the CP and control groups when evaluated by univariate and multivariate analyses. Likewise, no difference was observed regarding grade 3-4 hematological toxicities or reasons for treatment interruption.

Conclusion: This randomized study does not support the hypothesis that oral glutamine and TGF-β2 supplementation is effective to reduce grade 3 or 4 non-hematological toxicities induced by chemotherapy in patients with GI neoplasm.

Keywords: Chemotherapy; Gastrointestinal cancer; Immunonutrition; Side effects.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Cachexia / complications
  • Dietary Supplements*
  • Double-Blind Method
  • Female
  • Fluorouracil / administration & dosage
  • Gastrointestinal Diseases / chemically induced*
  • Gastrointestinal Diseases / prevention & control*
  • Gastrointestinal Neoplasms / complications
  • Gastrointestinal Neoplasms / drug therapy*
  • Glutamine / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Platinum Compounds / administration & dosage
  • Transforming Growth Factor beta / therapeutic use*

Substances

  • Platinum Compounds
  • Transforming Growth Factor beta
  • Glutamine
  • Fluorouracil