Prevention of Chemotherapy-related Oral Mucositis by Topical Timolol: A Prospective Randomized, Double-blind, Placebo-controlled Clinical Trial in Cancer Patients.

Abstract

Background: Timolol is a beta-adrenergic blocker that has been shown to be effective in the healing of wounds. Oral mucositis (OM), an acute inflammation of the oral mucosa, is a bothersome side effect of some regimens of chemotherapy in which the oral mucosa becomes ulcerated. The current study aimed to evaluate the prophylactic effects of timolol mouthwash in preventing OM in adult patients receiving chemotherapy compared to the placebo.

Method: This randomized, double-blind trial was conducted on 30 adult patients receiving chemotherapy regimen, including doxorubicin or 5-fluorouracil (5-FU). The patients were randomized in a 1:1 ratio to receive either timolol 0.5% (w/v) (n = 15) or placebo (n = 15) mouthwash 5 ml three times per day. The outcomes of the study were the intensity of OM evaluated by the World Health Organization (WHO) mucositis scale and OM-related pain based on the Visual Analog Scale (VAS) weekly during the seven weeks of the study period.

Results: The results of the study showed that the scores of WHO mucositis scale significantly decreased in the timolol group compared to the control group during the study [week 1: mean (SD), 0.02 (0.41) in the timolol group, and 0.67 (0.48) in the control group; week 7: mean (SD), 0.33 (0.61) in the timolol group, and 0.87 (0.74) in the control group; P-value = 0.049]. Moreover, the mean pain scores significantly decreased in the first, second, and third weeks in the timolol group compared to the control group (P-value < 0.05).

Conclusion: The results of this preliminary clinical trial demonstrated that among the patients receiving doxorubicin or 5-FU chemotherapy regimens, the preventive use of timolol mouthwash significantly diminished the severity of OM compared to the control group during the seven weeks of follow-up. The severity of pain was also significantly lower during the first three weeks of the study; however, the effect size was less than the minimal clinically important difference. Further studies are required to assess both the long-term efficacy and safety of timolol mouthwash in preventing OM.