Abstract CT122: RCT of an herbal mouthrinse for radiotherapy induced oral mucositis in cancer patients
Authors: Reed Susan G. , Cunningham Joan E. , Garrett-Mayer Elizabeth , Mulligan Jennifer L. , Fields Laura D. , Boyle Lynsey R. , Daanen Sarah P. , Keller John H. , Roach Casey L. , Pasquini Whitney C. , Lawrence Lauren , Harmon Howell , Garrett Ahmad R. , Wargovich Michael J. , Sharma Anand K. 
Published: August 2015

Abstract
Objectives: Primary aim of the ongoing study (NCT01898091) is to determine whether a mouthrinse containing extract of neem leaf (Azadirachta indica A. Juss.), a tropical evergreen tree with anti-inflammatory and anti-microbial medicinal properties, will lessen the severity of oral mucositis (OM) in patients undergoing radiation therapy (RT) to the head and neck. Secondary aims are to assess the effects of the neem mouthrinse on the microbial environment of the oral cavity and on quality of life.
Methods: Design is a double-blind, controlled, randomized, parallel-group Phase II clinical trial at a single NCI designated center. Block-randomization was used for patient assignment, stratified by tobacco use. Eligibles were adults with histologically confirmed head and neck cancer (HNC) whose treatment includes RT for 7 weeks. HNC includes malignancy of the oral cavity, oro-pharynx and larynx (ICD-9 codes 140 - 149, 161; ICD-O morphology code of 2 or 3). Exclusion criteria include prior HNC radiotherapy, baseline mouth and throat soreness (MTS) score of &gt;3, ECOG performance status &gt;2, allergy or inability to use mouthrinse, and language barrier. Evaluable participants receive &gt; 40 Gy RT and participate to week 6 RT. Study duration is 12 weeks with visits at baseline, weekly during RT, 3 telephone visits post RT, and one-month follow-up visit. Data were collected using the Oral Mucositis Daily Questionnaire, Functional Assessment of Cancer Therapy-Head and Neck, and Symptom Distress Scale questionnaires; CariScreen for oral microbial load, and ELISA and flow cytometry for salivary analyte measures.
Results: Of 53 patients enrolled, 3 screen failed and 8 withdrew leaving 42 with evaluable data. Neem (n = 23) and placebo (n = 19) groups were not statistically different for demographic and clinical variables. Major hypothesis assessed as the maximum change in MTS score from baseline during 6 weeks of RT resulted in a larger change, 1.91 with SD 1.34 for neem group vs. 1.71 with SD 1.29 for placebo group based on a Wilcoxon rank sum test with one-sided alpha = 0.05. Preliminary results suggest no difference in the maximum change in severity from baseline (p = 0.85). Neem group had higher adherence to mouthrinse protocol measured as ≥4 days mouthrinse use per week for six weeks (OR 2.56, p = 0.19). Additional outcomes of ongoing comparisons across groups include time to maximum OM severity, time to onset of OM, percent of patients with MTS scores &lt;3, and percent of patients by levels of change in MTS score. Regression analyses will be used to assess relationships between maximum and temporal changes in MTS score and mouthrinse group, adjusted for baseline characteristics and pertinent events. Relationships between changes in MTS score and mouthrinse usage over the time-course of the study will also be explored by graphical comparisons and regression approaches. Time to event outcomes will be assessed using Kaplan-Meier curves and comparisons will be made by log rank tests. Due to sample size, these latter analyses will be exploratory.
Citation Format: Susan G. Reed, Joan E. Cunningham, Elizabeth Garrett-Mayer, Jennifer L. Mulligan, Laura D. Fields, Lynsey R. Boyle, Sarah P. Daanen, John H. Keller, Casey L. Roach, Whitney C. Pasquini, Lauren Lawrence, Howell Harmon, Ahmad R. Garrett, Michael J. Wargovich, Anand K. Sharma. RCT of an herbal mouthrinse for radiotherapy induced oral mucositis in cancer patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT122. doi:10.1158/1538-7445.AM2015-CT122