Cerchietti, L.C., Navigante, A.H., Lutteral, M.A., Castro, M.A., Kirchuck, R., Bonomi, M., … Uchima, P. (2006). Double-blinded, placebo-controlled trial on intravenous L-alanyl-L-glutamine in the incidence of oral mucositis following chemoradiotherapy in patients with head-and-neck cancer. International Journal of Radiation Oncology, Biology, Physics, 65, 1330–1337.

Patients were randomized to receive IV L-alanyl-L-gluatime 0.3 g/kg (30 infusions in 5 patients) or 0.4 mg/kg (25 infusions in 5 patients), administered at a rate of 0.1 g/kg body weight/h. The principal endpoint was incidence of mucositis (mean of three highest scores by Objective Mucositis Assessment Score (OMAS) and highest grade on World Health Organization [WHO] scale).

• The sample consisted of 29 patients, 15 in the placebo group and 14 in the treatment group.
• All patients had unresectable head and neck cancer and received cisplatin and fluorouracil (5-FU) followed by concurrent chemotherapy and radiation.
• Patients with severe renal or hepatic insufficiency were excluded from the study. 
• No patients received steroids or antimicrobials prior to the study. No patients received any measure intended to prevent mucositis, although the authors did not indicate what standard oral care included.

The study used a two-step design. Patients were randomized first to different doses of the glutamine intervention, then to placebo (double-blind).

OMAS and WHO grading scale were used.

• OMS values were lower in the treatment group (1.33 in the placebo group versus 0.82 in the glutamine group) (p = 0.044).
• The mean WHO score was lower in the treatment group (2 versus 3) (p = 0.035).
• The OMS and WHO score correlation was significant (r = 0.83, p < 0.0001).
• Nine patients in the placebo group required feeding tubes compared to two patients in the treatment arm (p = 0.020).
• Patients in the treatment arm reported less pain (p = 0.008) and required fewer opioids (p = 0.025).

Measurement using both mucositis scales indicated a significant difference in intensity of mucositis.

• The study sample was small.
• Intensive nutritional support was used in both groups.
• All patients were supplemented with oral formulas containing no glutamine.
• Some question exists regarding whether glutamine can be a fuel for rapidly proliferating tumors; other studies have failed to demonstrate this effect.