Researchers have reported a reduction in the incidence of mucositis among women receiving chemotherapy for breast cancer who received the investigative solution AES-14 (Saforis).
The substance transports saliva-dependent L-glutamine into glands in the mouth, said Douglas Peterson, DMD, PhD, Head of the Department of Oral Diagnosis at the School of Dental Medicine and Associate Director of the Cancer Center at the University of Connecticut Health Center, reporting the results at a poster study at the San Antonio Breast Cancer Symposium.
“To our knowledge, this study represents the first Phase III randomized clinical trial to meet a primary endpoint of reducing oral mucositis incidence in the largest population at risk—patients with solid tumors who are undergoing nonmyeloablative combination chemotherapy.”
In the trial reported at the meeting, 326 patients were randomized to receive 5 ml of placebo suspension or 5 ml of AES-14 in a crossover design.
After diagnosis of mucositis according to World Health Organization criteria, patients were randomized equally to an anthracycline-based regimen and either AES-14 or placebo. After one cycle of treatment the patients were crossed over to either placebo or AES-14 and received another chemotherapy treatment. They were then assessed for mucositis.
About 50% of placebo patients developed Grade 2 mucositis in the trial compared with 39% of patients receiving AES-14. Thirteen patients developed Grade 3 mucositis—two patients receiving AES-14, 11 on placebo—a difference that was also statistically significant.
In the second cycle, patients receiving placebo had a mucositis rate of 18.4%, indicating a significant carryover preventive impact of previous AES-14 use.
Commenting on the study, mucositis expert Ricardo Spielberger, MD, a staff physician at City of Hope Cancer Center, noted that previous studies with the agent in which all patients were treated resulted in no differences in outcomes.
“It would be interesting to study the effect of AES-14 in men as well,” he said, noting that it would also be interesting to study it not only during chemotherapy cycles but also in between cycles if there is glutamine depletion in these patients.
He also suggested that quality-of-life surveys should be performed among the patients taking the drug.
“Oral mucositis is a dose-limiting complication of chemotherapy for many breast cancer patients and is associated with increased patient morbidity, impaired nutrition, and decreased quality of life,” Dr. Peterson said. “There is no approved drug to prevent or reduce the duration and severity of mucositis.”
Patients “swished” 5 ml of either placebo or AES-14 in their mouths for about 30 seconds before swallowing the liquid. They performed that task three times a day and were asked to refrain from eating until 30 minutes after taking the drug.
“As with most drugs for treatment of these conditions, AES-14 is not a home run,” Dr. Peterson said. “I would anticipate it will be used with other medications in these patients.”
The study was supported by Aesgen, Inc., which was acquired by MGI Pharma in September.
“Mucositis has been a big problem in treating patients with anthracycline-based regimens,” noted Clifford Hudis, MD, Chief of the Breast Cancer Medicine Service at Memorial Sloan-Kettering Cancer Center.
“If this treatment can improve the quality of life of the patients taking chemotherapy it may make these regimens more tolerable and that can be life saving.”
AES-14 is a suspension of L-glutamine in a proprietary delivery vehicle that enhances transport of 100 times more L-glutamine into cells than convention L-glutamine in as little as 10 seconds.