Abstract 4160: A new orotopically applied vasoconstrictor drug significantly confers normal oral mucosa resistance to radio-damage
Authors: Graul-Conroy Amanda , Hoover-Regan Margo , Sondel Paul M. , Callander Natalie S. , Longo Walter L. , Li Ningfeng F. , Fahl William E. 
Published: August 2018

Abstract
Introduction: Oral mucositis (OM) represents one of the most debilitating and troublesome adverse effects of chemoradiotherapy frequently encountered in patients. Most ionizing radiation-induced oral mucosa cell death results from radiation-induced reactive oxygen species (ROS) attack of DNA bases and molecular oxygen (O2) “fixation” of the ROS damage, which results in DNA breakage. Our earlier work showed complete suppression of radiation-induced oral mucositis in rodents by transient reduction of ROS related DNA damage when the animals were pre-treated with a topically-applied vasoconstrictor before irradiation. In this study, we have initiated a Phase IIa clinical investigation to determine whether orotopical vasoconstrictor application conferred the same resistance to radio-damage in normal oral mucosa of patients receiving whole-body radiation prior to bone marrow transplantation. Patients and Methods: In two years, 58 patients received the cyclophosphamide +TBI conditioning regimen. A clinical trial (NCT02434146) was approved by the University of Wisconsin Review Board to test the ability of five increasing doses of the NG-11-1 topical vasoconstrictor formulation to suppress the incidence and severity of OM. For a control cohort, records of five patients who received the cyclophosphamide+TBI regimen at UW were analyzed, records including weights, daily OM scores, use of total parenteral nutrition (TPN) were collected for comparison to the NG-11-1 treatment group. For the “topical NG-11-1 treated” group, each patient received the lowest of the five projected concentrations of NG-11-1 vasoconstrictor. The study physician directed 30 spray pulses to the buccal, lingual and sub-lingual surfaces. The formulation contains a blue coloring that enables directing and judging drug coverage. Orotopical NG-11-1 was applied: i) 15-20 min before IV cyclophosphamide was initiated, ii) 25-30 min after IV cyclophosphamide was initiated, and iii) 15-20 min before every 1.5 Gy irradiation. Pain score and OM score were collected before and after treatments and during follow-up clinic re-visits for 2 weeks. Results: The mean of “Grade 3 oral mucositis duration (days)” in NG-11-1 vasoconstrictor drug treated patients was significantly lower (P=0.047) than that of control patients. And, the mean of “total mucositis duration (days)” in NG-11-1 treated patients was significantly lower (P=0.043) than the level of control patients. Thirdly, either nasogastric feeding or total parenteral nutrition was required in 60% of control patients, however, none of the NG-11-1-treated patients required this intervention. Conclusions: These clinical results showing significant suppression of OM severity are consistent with the same degree of NG-11-1 dose-dependent suppression of radiation-induced oral mucositis that we observed in our previous mouse OM model studies.
Citation Format: Amanda Graul-Conroy, Margo Hoover-Regan, Paul M. Sondel, Natalie S. Callander, Walter L. Longo, Ningfeng F. Li, William E. Fahl. A new orotopically applied vasoconstrictor drug significantly confers normal oral mucosa resistance to radio-damage [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4160.