Herbal Mouthrinse for Oral Mucositis Study

The broad goal of our research is development of an effective Complementary and Alternative Medicine (CAM) approach to prevent mucositis or lessen its severity and complications. Oral mucositis (OM) is a clinically challenging and debilitating side effect of conventional radiotherapy (RT), affecting almost all patients undergoing RT for head and neck cancer. OM includes inflammation of the oral mucosa with or without opportunistic microbial infection. It ranges from mild erythema to severe ulceration accompanied by persistent pain leading to inability to tolerate or swallow food and fluids. OM frequently causes unwanted cancer treatment dose reductions or breaks in therapy. Despite use of pain medications, severe OM is associated with substantially increased use of costly health care resources. Presently, there are no effective treatments for OM. The primary aim of the current proposal is to determine whether or not a mouthrinse containing an herbal extract with known anti-inflammatory and anti-microbial medicinal properties, will reduce the severity of oral mucositis in cancer patients undergoing conventional radiotherapy to the head and neck. Because of the prominent inflammatory and microbial aspects of OM we anticipate that the herbal mouthrinse will reduce the severity of the pain and secondary infections associated with OM, and will improve the quality of life in head and neck cancer patients undergoing RT. Therefore, the specific aims of our Phase II double-blind, randomized, controlled trial are 1) to determine if the severity of oral mucositis is reduced in RT patients receiving the herbal mouthrinse compared to patients receiving the comparison mouthrinse and 2) to determine the effects of the herbal mouthrinse on the microbial environment of the oral cavity and on quality of life. Findings from this study will provide evidence to support more in-depth biological assessment of the anti-inflammatory and anti-microbial mechanisms by which the herbal extract reduces oral mucositis, and additional study in other populations experiencing mucositis.

• Neem Mouthrinse (Drug), also known as aloe, anise, ascorbic acid, clove, glycerin, extract of neem leaf, peppermint, poloxamer 407, potassium sorbate, spearmint, thyme, water, xylitol: 10ml dose of assigned study mouthrinse, three times per day, for approximately 7 weeks during radiation therapy.
• Placebo Mouthrinse (Drug), also known as aloe, anise, ascorbic acid, clove, glycerin, peppermint, poloxamer 407, potassium sorbate, spearmint, thyme, water, xylitol: 10ml dose of assigned study mouthrinse, three times per day, for approximately 7 weeks during radiation therapy.

Primary outcomes

• Maximum Change in Mean Mouth and Throat Soreness (MTS) Score From Baseline Through Weeks of Radiation Therapy Using the MTS Question of the Modified Oral Mucositis Daily Questionnaire*. [MTS score is collected at the baseline visit and once each week during the 7 weeks of radiation therapy.]: Severity is assessed as the maximum change in mean mouth and throat soreness (MTS) score from baseline during the weeks of RT, using MTS question of the validated Oral Mucositis Daily Questionnaire (modified OMDQ): "During the past 24 hours, how much mouth and throat soreness did you have?" The MTS score is a 5-point score, ranging from 0=No soreness to 4=Extreme soreness. We compared the maximum change in MTS score between the two groups using the Wilcoxon rank sum test with a one-sided alpha of 0.05.

Sex: All, ages: 18 Years to 89 Years

Inclusion Criteria:

* Anatomic site: lip (inner aspect), oral cavity, pharynx or larynx; includes tonsils and salivary glands (ICD-9: 140-149 or 161).
* Malignant tumor: ICD-O morphology 2 (in situ) or 3 (malignant, invasive or infiltrating).
* Adult aged 18-89 years.
* Patient recommended or planned to undergo radiotherapy to the head and neck regions, as part of their cancer treatment regimen.
* Radiotherapy to be given in standard doses over a 4 - 7 week period.

Exclusion Criteria:

* Prior radiation treatment for cancer of the oral cavity, head or neck.
* Baseline mouth and throat soreness (MTS) extreme score of 4.
* Eastern Cooperative Oncology Group (ECOG) performance status >2.
* Unable to sign Informed Consent.
* Known history of allergy to any of the mouthrinse constituents (aloe, anise, ascorbic acid, clove, glycerin, peppermint, poloxamer 407, potassium sorbate, spearmint, thyme, water, xylitol).
* Inability to use a mouth rinse.
* Patient unable to communicate with study personnel in English (either themselves or an interpreter).

Participant flow

Outcome results

• Maximum Change in Mean Mouth and Throat Soreness (MTS) Score From Baseline Through Weeks of Radiation Therapy Using the MTS Question of the Modified Oral Mucositis Daily Questionnaire*. (Primary), Mean, units on a scale: Neem Mouthrinse 1.91 +/- 1.34; Placebo Mouthrinse 1.47 +/- 1.22 (p 0.84)

Adverse events

Time frame: 12 weeks

Serious adverse events by term

Other adverse events by term

• Results publication: Elting LS, Keefe DM, Sonis ST, Garden AS, Spijkervet FK, Barasch A, Tishler RB, Canty TP, Kudrimoti MK, Vera-Llonch M; Burden of Illness Head and Neck Writing Committee. Patient-reported measurements of oral mucositis in head and neck cancer patients treated with radiotherapy with or without chemotherapy: demonstration of increased frequency, severity, resistance to palliation, and impact on quality of life. Cancer. 2008 Nov 15;113(10):2704-13. doi: 10.1002/cncr.23898. PMID 18973181

• Susan G. Reed, DDS, DrPH, Principal investigator, Medical University of South Carolina

NIH grants: R21CA158530