Skin tumor development after UV irradiation and photodynamic therapy is unaffected by short-term pretreatment with 5-fluorouracil, imiquimod and calcipotriol. An experimental hairless mouse study

Abstract

BackgroundPhotodynamic therapy (PDT) delays ultraviolet (UV) radiation-induced squamous cell carcinomas (SCCs) in hairless mice. Efficacy may be enhanced by combining PDT with antineoplastic or pro-differentiating agents. We investigated if pretreatment with 5-fluorouracil (5FU), imiquimod (IMIQ) or calcipotriol (CAL) before PDT further delays tumor onset. MethodsHairless mice (n=224) were exposed 3 times weekly to 3 standard erythema doses (SED) of UV radiation. Methyl-aminolevulinate (MAL)-PDT sessions were given on days 45 and 90 before SCC development. Three applications of topical 5FU, IMIQ or CAL were given before each PDT session. Fluorescence photography quantified protoporphyrin IX (PpIX) formation. ResultsPDT delayed UV-induced SCC development by 59days (212days UV-MAL-PDT vs. 153days UV-control, P<0.001). Pretreatment with 5FU, IMIQ or CAL before PDT did not further delay SCC onset compared to PDT alone (207days UV-5FU-MAL-PDT, 215days UV-IMIQ-MAL-PDT, 206days UV-CAL-MAL-PDT vs. 212days UV-MAL-PDT, P=ns). PpIX fluorescence intensified by 5FU-pretreatment (median 21,392au UV-5FU-MAL-PDT, P=0.011), decreased after IMIQ-pretreatment (12,452au UV-IMIQ-MAL-PDT, P<0.001), and was unaffected by CAL-pretreatment (19,567au UV-CAL-MAL-PDT, P=ns) compared to MAL alone (18,083au UV-MAL-PDT). ConclusionsShort-term three-day pretreatment with 5FU, IMIQ and CAL before PDT does not further delay tumor onset in UV-exposed hairless mice.