Double-blind placebo-controlled multicenter phase II trial to evaluate D-methionine in preventing/reducing oral mucositis induced by radiation and chemotherapy for head and neck cancer

Head Neck. 2018 Jul;40(7):1375-1388. doi: 10.1002/hed.25115. Epub 2018 Feb 23.

Abstract

Background: The purpose of this study was to test if oral D-methionine (D-met) reduced mucositis during chemoradiotherapy.

Methods: We conducted a placebo-controlled double-blind randomized phase II trial of D-met (100 mg/kg p.o. b.i.d.) testing the rate of severe (grades 3-4) mucositis.

Results: Sixty patients were randomized. Grade 2 + oral pain was higher with placebo (79% vs 45%; P = .0165), whereas grade 2 + body odor was greater with D-met (3% vs 41%; P = .0015). Mucositis was decreased with D-met by the physician (World Health Organization [WHO], P = .007; Radiation Therapy Oncology Group [RTOG], P = .009) and patient functional scales (RTOG, P = .0023). The primary end point of grades 3 to 4 mucositis on the composite scale demonstrated a decrease with D-met (48% vs 24%; P = .058), which was borderline in significance. A planned secondary analysis of a semiquantitative scoring system noted decreased oral ulceration (2.2 vs 1.5; P = .023) and erythema (1.6 vs 1.1; P = .048) with D-met.

Conclusion: Although not meeting the primary end point, results of multiple assessments suggest that D-met decreased mucositis.

Keywords: clinical trial; mucositis; radioprotector; radiotherapy; toxicity.

Publication types

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

MeSH terms

  • Administration, Oral
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Carcinoma, Squamous Cell / therapy
  • Chemotherapy, Adjuvant / adverse effects*
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Double-Blind Method
  • Female
  • Head and Neck Neoplasms / therapy*
  • Humans
  • Male
  • Methionine / therapeutic use*
  • Middle Aged
  • Radiotherapy, Adjuvant / adverse effects*
  • Stomatitis / classification
  • Stomatitis / etiology
  • Stomatitis / prevention & control*

Substances

  • Antineoplastic Agents
  • Methionine
  • Cisplatin