Abstract B130: Radiodermatitis prevention by topical norepinephrine in post-surgical breast cancer patients
Authors: Cleary James F. , Anderson Bethany M. , Eickhoff Jens C. , Khuntia Deepak , Fahl William E. , Thunberg Allen L. 
Published: May 2015

Abstract
Purpose: This study was a feasibility and exploratory study to evaluate the safety and efficacy of topical norepinephrine in preventing radiodermatitis in patients receiving whole breast external beam radiation therapy after breast conserving surgery.
Materials & Methods: In preclinical experiments to test whether co-application of a topical vasoconstrictor would limit the systemic uptake of a topically applied, radioprotective, oxygen free radical scavenger, it was observed that the vasoconstrictor alone was radioprotective, preventing radiation dermatitis when administered alone as a control. This radioprotection is consistent with a mechanism based on local, transient vasoconstriction within the skin, which reduces local tissue oxygenation, limits the formation of radiation-induced reactive oxygen species, and protects skin stem cells from radiation damage. Topical norepinephrine was well tolerated in two Phase I safety studies conducted prior to this study, one in normal volunteers and one in cancer patients receiving palliative radiation therapy for bone metastases. Tested doses elicited transient skin blanch, which is indicative of reduced blood flow secondary to local vasoconstriction, but did not induce blood pressure elevation, local skin necrosis, or any other significant adverse event. Most of the adverse events that were possibly, probably, or definitely related to study medication were mild skin reactions, typically including pruritis, that occurred at or near the application site. There were no serious adverse events.
The present study was a nonrandomized, open-label safety and exploratory study in post-surgical breast cancer patients treated with 45 to 50 Gray to the whole breast. A 10-16 Gray boost to the lumpectomy region was permitted. Eligible patients were women, age 18 years or older, who underwent breast conserving surgery for Stage Ia (T1, N0, M0), Stage Ib (T0 or 1, N1mic, M0) or Stage IIa (T&lt;3cm, N0, M0) infiltrating ductal or lobular carcinoma of the breast or ductal carcinoma in situ (DCIS). The radioprotectant dose was a topical application of 3.0 mL of norepinephrine HCl (82.3 mg/mL in 70% ethanol) applied to the same 50-cm2 treatment site within the lateral aspect of the whole breast radiation field (i.e. in or near the axilla) about 20 minutes prior to each daily radiotherapy fraction.
Results: 10 patients completed the protocol. No new safety concerns were identified. There were no serious adverse events, and no occurrences of norepinephrine-associated damage to irradiated skin. Assessments of radiodermatitis severity at the treatment site provided evidence for local reductions in radiodermatitis severity, compared to surrounding (untreated) control areas, in a majority of the treated patients.
Conclusions: Topical norepinephrine demonstrated promising preliminary results in reducing radiation dermatitis in women undergoing whole breast irradiation, with minimal toxicity. Dose escalation, an expansion of the dose volume to permit the treatment of the entire skin area at risk for radiodermatitis, will precede a randomized, placebo-controlled evaluation of safety and efficacy. NCT01263366.
Citation Format: James F. Cleary, Bethany M. Anderson, Jens C. Eickhoff, Deepak Khuntia, William E. Fahl, Allen L. Thunberg. Radiodermatitis prevention by topical norepinephrine in post-surgical breast cancer patients. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research: Genetics, Biology, and Clinical Applications; Oct 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2013;11(10 Suppl):Abstract nr B130.