A new strategy to prevent chemotherapy and radiotherapy-induced alopecia using topically applied vasoconstrictor

Abstract

In a new strategy, we sought to determine whether topically applied vasoconstrictor, with its accompanying transient skin hypoxia and exclusion of systemic drug, would prevent or suppress radiotherapy or chemotherapy-induced alopecia. Topical vasoconstrictor was applied to 1-cm2 skin patches on the backs of 10-day-old rats and minutes later they received either 7.1 gray (Gy) whole-body radiation or systemic N-nitroso-N-methylurea (MNU) or Cytoxan. The degree of alopecia was scored 10 days later by visual assessment (% coat retention) and hair follicle histologic analysis. Topical application of epinephrine or norepinephrine in an alcohol:water delivery vehicle induced clear skin blanch, and in a dose-dependent manner, topical epinephrine or norepinephrine (20–1,000 mM) applied before 7.1 Gy irradiation conferred 95% of coat retention in the treated skin patches versus 0% coat retention in vehicle controls, or in skin outside the treated patches. By histology, small numbers of dystrophic hair follicles were observed in hairless skin versus the normal density of anagen follicles in the immediately adjacent, drug-protected skin patches at day 20; protected coats were retained into adulthood. Topical epinephrine or norepinephrine before systemic MNU (30 ug/gm body weight) conferred up to 95% of coat retention in treated skin patches versus 0% coat retention elsewhere. Epinephrine-conferred % coat retention dropped to 16% in rats that received systemic Cytoxan, a drug whose plasma half-life is at least 8- to 10-fold longer than MNU. A general strategy is discussed for the use of topical epinephrine or norepinephrine in the clinic to provide an inexpensive and convenient strategy to prevent cancer therapy-induced alopecia.

Radiation-Induced Alopecia after Endovascular Embolization under Fluoroscopy

“…Complete hair regrowth generally occurs within 2–4 months after irradiation [10–14]. In addition, no treatment or preventive measures appear to be generally effective [19, 20]. To prevent this unwanted effect, awareness and limitation of radiation exposure to the patient are the most important.…”

“…To prevent this unwanted effect, awareness and limitation of radiation exposure to the patient are the most important. Although topical application of epinephrine or norepinephrine before radiation was found to confer up to 95% coat retention in a rat model, further studies in human are required to indicate its efficacy [19]. Online monitoring of the patient's radiation exposure is also necessary because fluoroscopy time does not account for either fluoroscopic dose rates or the use of fluorographic acquisition modes during a procedure.…”

Norepinephrine Regulates Keratinocyte Proliferation to Promote the Growth of Hair Follicles

“…A recent study reported that topical application of the α-adrenergic vasoconstrictors epinephrine or NE to the skin of neonatal rats before a considerable radiation or chemotherapeutic insult prevented up to 100% of the alopecia observed in CTR animals [Soref and Fahl, 2015]. Chemotherapy-induced alopecia may be attributed to peripheral neurotoxic effects Dietrich et al, 2015], thus explaining why application of epinephrine or NE suppressed alopecia.…”

Optimum Topical Delivery of Adrenergic Agonists to Oral Mucosa Vasculature

“…A strategy involving topical vasoconstrictor application for preventing radiotherapy and chemotherapy toxicities to skin and its organelles has emerged and has been proven effective in a preclinical study demonstrating suppression of radiation-or chemotherapy-induced alopecia (7) as well as in both preclinical and clinical studies showing up to 100% prevention of radiation dermatitis (8,9). A recent preclinical study has also shown efficacy of topical vasoconstrictor in suppression of oral mucositis in two separate animal models (10).…”