A new topical vasoconstrictor-based strategy for prevention of oral mucositis.
OBJECTIVE
In a new strategy, we sought to determine whether vasoconstriction and transient hypoxia of the mucosa during irradiation would prevent or suppress radiation-induced oral mucositis.


METHODS
Topical vasoconstrictor was applied once to the oral cavity; 20 minutes later hamsters or mice received 19 to 30 Gy to the mucosa. Oral mucositis was scored using functional assay, gross morphology, and histology of mucosal tissue over the next 12 to 16 days.


RESULTS
A single application of phenylephrine (14 mM to 136 mM) 20 minutes before irradiation conferred highly significant (P < .001), dose-dependent suppression of weight loss, oral secretion, and histopathology of mucosa seen in mice treated with 0 mM phenylephrine + 19-Gy irradiation. Epinephrine, norepinephrine, and phenylephrine showed up to 100% radioprotective efficacy at concentrations that reflected their rank-ordered affinities for the α1-adrenergic receptor.


CONCLUSIONS
Phenylephrine swish-and-spit application before radiotherapy, or multiple applications during chemotherapy, may provide a simple, cost-effective strategy for suppression of oral mucositis in patients undergoing radiotherapy, chemotherapy, or bone marrow transplant.
McArdle Laboratory for Cancer Research, University of Wisconsin Carbone Cancer Center, Madison, WI, USA; ProCertus BioPharm Inc, Madison, WI, USA.
Cheryl M
CM
Soref
McArdle Laboratory for Cancer Research, University of Wisconsin Carbone Cancer Center, Madison, WI, USA; ProCertus BioPharm Inc, Madison, WI, USA. Electronic address: fahl@oncology.wisc.edu.
William E
WE
Fahl
D000287:Administration, Topical; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D051379:Mice; D009061:Mouth Mucosa / Q000187:drug effects* / Q000528:radiation effects*; D010656:Phenylephrine / Q000008:administration & dosage / Q000494:pharmacology*; D011878:Radiotherapy / Q000009:adverse effects; D013280:Stomatitis / Q000209:etiology / Q000517:prevention & control*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014945:Wound Healing
D000970:Antineoplastic Agents; D014662:Vasoconstrictor Agents; D010656:Phenylephrine