• 8/8/2006
  • Iowa City, IA
  • staff
  • CancerConsultants.com

Researchers from Argentina have reported that the intravenous administration of L-alanyl-L-glutamine was effective in reducing the incidence and severity of oral mucositis following chemotherapy for head and neck cancer.[1] The details of this randomized trial appeared in the August 1, 2006, issue of the International Journal of Radiation Oncology Biology Physics .

Oral mucositis is a significant complication of cancer chemotherapy and radiation therapy. Several approaches have been used to decrease the incidence and severity of mucositis, including local cryotherapy, the administration of Ethyol (amifostine), and the administration of growth factors including Kepivance® (ketatinocyte growth factor), which is approved by the U.S. FDA for prevention of oral mucositis in patients receiving autologous stem cell transplants. L- glutamine is of interest in preventing oral mucositis as it is an essential amino acid involved in cellular repair. L-glutamine has also been used as a supplement in parenteral nutrition preparations with some evidence that it prevents infections in debilitated patients.

L-glutamine as a preventative agent for oral mucositis has been studied as an oral agent. Previous studies of L-glutamine to prevent oral mucositis have involved an oral preparation called AES-14. AES 14 is combined with a vehicle (Saforis™), which enhances its availability to cells of the mucous membrane. This oral combination has been shown to favorably affect the course of chemotherapy-induced mucositis.[2] AES 14 is marketed by Aesgen and has fast tract designation by the FDA for treatment of oral mucositis.

The results of a randomized, double-blind, placebo-controlled, crossover, multi-center trial to determine the efficacy of AES-14 delivered in the proprietary base, Saforis ™ in reducing the severity and duration of oral mucositis was presented at the 2004 ASCO Annual Meeting.[3] In this study, 326 breast cancer patients received an anthracycline-based regimen along with AES-14 or placebo over two subsequent crossover cycles. AES-14 reduced the incidence of clinically significant oral mucositis by 22% compared to the placebo group, while maintaining an excellent safety profile that was comparable to placebo. Unexpectedly, patients who crossed over from AES-14 to placebo had a 36% lower incidence of oral mucositis, suggesting a carryover benefit.

In the current study, 29 patients with head and neck cancer receiving chemoradiotherapy were randomly allocated to receive daily L-glutamine or placebo intravenously. They reported that the control group had a 67% incidence of severe oral mucositis compared to 14% in the L-glutamine group. They also reported less pain in the treated group compared to the control group. In the control group, 60% of patients required a feeding tube compared to 14% in the L-glutamine group. There were apparently no adverse side effects of L-glutamine.

Comments: It would appear that both the oral form as AES14 and the IV of form as L-alanyl-L-glutamine have significant activity in preventing oral mucositis. The FDA status of IV L-alanyl-L-glutamine is unclear, but it is apparently added to parenteral feedings at the present time.

References
[1] Cerchietti LCA, Navignate AH, Lutteral MA, et al. Double-blinded, placebo-controlled trial on intravenous L-alanyl-Lglutamine in the incidence of oral mucositis following chemotherapy in patients with head and neck cancer. International Journal of Radiation Oncology Biology Physics. 2006;65:1330-1337.
[2] Savarese DM, Savy G, Vahdat L, et al. Prevention of chemotherapy and radiation toxicity with glutamine. Cancer Treat Rev . 2003;29:501-13.
[3] Peterson DE, Petit RG. Phase III study: AES-14 in patients at risk for mucositis secondary to anthracycline-based chemotherapy. Proc Am Soc Clin Oncol. 22:2917, 2003. Abstract #8008.