Mouthwash reduces radiation-induced oral mucositis pain among patients with head and neck cancer
A mouthwash consisting of diphenhydramine, lidocaine and antacids significantly reduced pain from oral mucositis among patients receiving radiation for head and neck cancer, according to results of a randomized phase 3 trial published in JAMA.
“Radiation therapy may cause mouth sores because it is designed to kill rapidly growing cells, such as cancer cells,” Terence Tai-Weng Sio, MD, MS, assistant professor of radiation oncology and radiation oncologist at Mayo Clinic in Phoenix, said in a press release. “Unfortunately, healthy cells in the mouth also divide and grow rapidly, and may be damaged during radiation therapy, which can cause discomfort. We are glad to have identified a proven method to help treat the discomfort of this side effect.”
Sio and colleagues evaluated 275 patients (mean age, 61 years; 21% women) who underwent radiotherapy for head and neck cancer and had an oral mucositis pain score of 4 points or higher on a scale of 0 to 10.
The researchers randomly assigned patients to a doxepin mouthwash (n = 92), a diphenhydramine-lidocaine-antacid mouthwash (n = 91) or placebo (n = 92).
Results showed those who received the diphenhydramine-lidocaine-antacid mouthwash experienced an 11.7-point decrease in mucositis pain during the first 4 hours after treatment, compared with an 11.6-point decrease with the doxepin mouthwash and an 8.7-point decrease with placebo.
HemOnc Today spoke with Sio about the study, what he and colleagues found, the clinical implications of the findings, and plans for future research.
Question: What prompted this research ?
Answer : We give chemotherapy and radiation to patients with head and neck cancer. Radiation can induce oral mucositis, which can be painful. So, we decided to conduct a symptom-control study to see if doxepin mouthwash and also a mixed mouthwash of diphenhydramine, lidocaine and antacids can relieve oral mucositis pain compared with placebo mouthwash. My group evaluated doxepin in a previous study in Journal of Clinical Oncology, which showed it was beneficial, but we needed a second study to confirm that doxepin mouthwash may be helpful to these patients. As for the mixed mouthwash, we had no first-level evidence from randomized trials to show that it is beneficial compared with placebo mouthwash.
Q: How did you conduct the current study?
A: We divided 275 patients into three treatment groups. All patients had undergone concurrent chemotherapy and radiation for head and neck cancer, which is usually 6 weeks to 7 weeks in duration. By the beginning of week 2 or week 3, patients may develop oral mucositis and open mouth sores, which cause pain. We required a score of 4 or higher on a 10-point scale for pain before the patient could be considered for the study. Once we identified a patient who also met a couple of other inclusion criteria, we randomly assigned the patient to doxepin mouthwash, the combination mouthwash or placebo mouthwash. Patients would take the first dose of the mouthwash in the clinic, and their pain would be documented at multiple time points. We then calculated changes in pain scores by the area under the curve (AUC). After that, the patients were enrolled in what we call an optional weekly regimen that allowed them to continue using the mouthwash every 4 hours as needed and to participate in a daily questionnaire.
Q: What did you find?
A: We found the AUC decreased by 2.9 points with the doxepin mouthwash vs. placebo, which was statistically significant. For the mixed mouthwash, there was a 3-point difference when compared with the placebo mouthwash, which also reached statistical significance. Thus, the primary endpoint was met. However, we expected to see a decrease in pain scores when compared with placebo of more than 3.5 points for clinical significance, which was the goal for the doxepin and the mixed mouthwash groups. As a result, there is a small concern over whether this is clinically meaningful for the average patient, and we discussed this in detail in the paper.
Q: What are t he clinical implications of the findings?
A: We now have two clinical trials showing that doxepin mouthwash relieved chemoradiotherapy-related oral mucositis pain, so it should become a standard of care. We also provided the first-ever evidence that the mixed mouthwash worked in a similar fashion for symptom control and relief. The study overall should be taken in a positive light.
Q: What is planned for future research?
A: We are planning a study to compare doxepin plus the mixed mouthwash with the mixed mouthwash alone. We want to do our best in helping our patients with cancer manage their pain and the complications associated with aggressive radiotherapy for head and neck cancers. – by Jennifer Southall
For more information:
Terence Tai-Weng Sio , MD, MS, can be reached at Mayo Clinic Arizona, 5777 E. Mayo Blvd., Phoenix, AZ 85054; email: Sio.Terence@mayo.edu.
Disclosure: Sio reports speaker/advisory board roles with Novocure Inc.