The efficacy of sodium azulene sulfonate L-glutamine for managing chemotherapy-induced oral mucositis in cancer patients: a prospective comparative study

Abstract

BackgroundThe efficacy of sodium azulene sulfonate L-glutamine (GA) in treating oral mucositis caused by the administration of anticancer agents has not been previously elucidated. Therefore, this prospective comparative study was conducted to evaluate the efficacy of GA in treating oral mucositis caused by chemotherapy regimens involving fluorinated pyrimidine anticancer drugs.MethodsThe subjects of this study were patients with oral mucositis of grade 2 or higher while on outpatient chemotherapy regimens involving fluorinated pyrimidine anticancer drugs for colorectal or breast cancer. The subjects were randomly divided into a group that received GA (the GA group) or a group that did not receive GA (the control group) by using the closed-envelope method. GA was administered three times a day every day from the first day of the regimen until the final day. The primary endpoint was the development of oral mucositis of grade 2 or higher. The secondary endpoint was the severity of oral pain, which was judged using an 11-stage numerical rating scale (NRS) ranging from 0 to 10.ResultsThe proportion of patients with oral mucositis of grade 2 or higher was 32.4% in the GA group and 57.6% in the control group. The GA group had a significantly lower frequency of occurrence. The changes in the NRS scores before and after the trial began were − 2.9 ± 0.6 in the GA group and − 1.2 ± 0.5 in the control group. The NRS score decreased more significantly in the GA group than in the control group (P = 0.046). One patient stopped GA treatment voluntarily due to nausea; other than nausea, no GA-related side effects were observed.ConclusionsGA protects against oral mucositis and reduces the severity of prevailing oral mucositis symptoms. Our findings indicate that GA is a highly safe and convenient drug.

Systematic review of natural and miscellaneous agents for the management of oral mucositis in cancer patients and clinical practice guidelines—part 1: vitamins, minerals, and nutritional supplements

“…Additionally, a large prospective cohort study has found oral glutamine to be effective in preventing OM [77]. Likewise, a non-blinded RCT in solid cancer patients treated with CT reported that glutamine formulated as sodium azulene sulfonate L-glutamine was effective in preventing OM [78].…”

Antitumor Effects and Tumor-specificity of Guaiazulene-3-Carboxylate Derivatives Against Oral Squamous Cell CarcinomaIn Vitro

“…The present study demonstrated that among twelve guaiazulene-3-carboxylates, two alkoxyl guaiazulene-3carboxylates [6,7] showed higher tumor-specificity than five alkyl [1][2][3][4][5] and two hydroxyalkyl [8,9] guaiazulene-3carboxylates and three aminoalkyl guaiazulene-3-carboxylate carboxamides [10][11][12] (Table I). Both [6,7] showed higher TS value than CDDP and CBDCA, and having comparable PSE value with 5-FU (Table I).…”

“…Methyl guaiazulene-3-carboxylate [1], ethyl guaiazulene-3-carboxylate [2], n-propyl guaiazulene-3-carboxylate [3], isopropyl guaiazulene-3carboxylate [4], n-butyl guaiazulene-3-carboxylate [5], 2methoxyethyl guaiazulene-3-carboxylate [6], 2-ethoxyethyl guaiazulene-3-carboxylate [7], 2-hydroxyethyl guaiazulene-3carboxylate [8], 2-(2-hydroxyethoxy)ethyl guaiazulene-3-carboxylate…”

“…We have repeated the same experiments 3 times. The mean values of CC 50 , tumor-selectivity index (TS), and potency-selectivity expression (PSE) of these twelve compounds, as well as of positive controls (5-FU, CDDP, and CBDCA) obtained from these 3 independent experiments are listed in PSE=13.0±1.9) showed the highest TS values than five alkyl guaiazulene-3-carboxylates [1][2][3][4][5], two hydroxyalkyl guaiazulene-3-carboxylates [8,9], and three aminoalkyl guaiazulene-3-carboxylates [10][11][12] (Table I). Moreover, both [6,7] showed higher TS value than CDDP and CBDCA (TS mean =2.2±1.5 and 2.4±1.1, respectively), and had PSE (mean) values comparable to that of 5-FU (13.4±6.5).…”

“…Among the 962 papers cited in PubMed regarding azulenes, most of them have focused on its chemistry, followed by biological activity, while few papers have focused on dentistry and oral application. Sodium azulene sulfonates have been reported to be effective for the treatment of oral mucositis (5) and oral lichen planus (6), possibly due to their antioxidant and anti-inflammatory activities (7,8). In contrast, much reduced numbers of papers of guaiazulene ( Figure 1B), a lipophilic azulene derivative, have been published, approximately half of which have dealt with its chemistry.…”