Peterson, D.E., Jones, J.B., & Petit, R.G., II. (2007). Randomized, placebo-controlled trial of Saforis for prevention and treatment of oral mucositis in breast cancer patients receiving anthracycline-based chemotherapy. Cancer, 109, 322–331.

• Glutamine (Saforis, MGI Pharma) was administered at 2.5 g per 5 ml, three times per day, for a total daily dose of 7.5 g. Treatment began on the first day of chemotherapy and continued for 14 days after the last dose in patients who did not develop oral mucositis or until 5 days after resolution of oral mucositis. Glutamine was orally swished for 30 seconds, then swallowed.
• Oral hygiene consisted of gently brushing teeth twice per day, 30 minutes or more after each study drug treatment, with a soft toothbrush and fluoride toothpaste. Daily flossing and alcohol-free fluoride rinse was recommended.
• All patients were treated with 200 mg oral acyclovir twice per day.

• Patients were eligible for the study if they
  • Were age 18 or older.
  • Had European Cooperative Oncology Group (ECOG) scores of 2 or less.
  • Had histopathologically confirmed breast cancer to be treated with anthracycline-based chemotherapy.
  • Experienced World Health Organization (WHO) grade 2 or higher mucositis during the first cycle of chemotherapy.
  • Were scheduled to receive at least two more cycles without dose reduction.
• In cycle 1, 163 patients received glutamine and 163 received placebo.
• In cycle 2, 150 patients received glutamine and 155 received placebo.

The study was conducted in Russia.

This was a randomized, double-blind, placebo-controlled, crossover, phase III trial.

• Oral mucositis was measured with regard to incidence, severity, ability to eat solid food, and pain.
• The WHO scale and Oral Mucositis Assessment Scale (OMAS) were used.

• Some nausea was reported.
• In treatment cycle 1, incidence of WHO grade 2 or higher was 38.7% in the treatment group and 49.7% in the placebo group (p = 0.026).
• Incidence of grade 3 or higher was 1.2% in the treatment group versus 6.7% in the control group (p = 0.005).
• Ability to eat solid food was 97.5% in the treatment group versus 91.9% in the control group (p = 0.039).
• No differences were observed in oral pain intensity or difficulty swallowing.
• In treatment cycle 2, incidence of WHO grade 2 or higher oral mucositis among patients in the placebo group was significantly lower than cycle 1 (31.9 versus 49.7; p = 0.0269); this was considered to be a carryover effect.

Glutamine is easy to use, has a favorable safety profile, and is low in cost. The total daily dose was within the range of dietary glutamine consumed by an adult on a high-protein diet (about 8 g per day). This treatment should be tested in higher intensity chemotherapy regimens.